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AT1 receptor

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 34

Nomenclature: AT1 receptor

Family: Angiotensin receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 359 3q24 AGTR1 angiotensin II receptor type 1 12,28,30,47,103
Mouse 7 359 13 16.0 cM Agtr1a angiotensin II receptor, type 1a 140,181
Mouse 7 359 3 7.6 cM Agtr1b angiotensin II receptor, type 1b 140,181
Rat 7 359 17q12 Agtr1a angiotensin II receptor, type 1a 67-68,85,113
Rat 7 359 2q24 Agtr1b angiotensin II receptor, type 1b 39,63,67,74,113,138,153,180
Gene and Protein Information Comments
Both rat and mouse have a second gene that codes for the AT1 receptor.
Previous and Unofficial Names Click here for help
AG2S | AT2R1 | AT2R1A | HAT1R | Agtr1 | angiotensin II type-1 receptor | angiotensin II type-1A receptor | angiotensin II type-1B receptor | AT3 | type-1A angiotensin II receptor | type-1B angiotensin II receptor | vascular type-1 angiotensin II receptor | Agtr-1b | Angtr-1b | Angtr-1a | AT1AR | AT1BR | Type-1 angiotensin II receptor | Agtr-1a | angiotensin II receptor, type 1 | angiotensin II receptor, type 1a | angiotensin II receptor, type 1b | angiotensin II receptor
Database Links Click here for help
Specialist databases
GPCRdb agtr1_human (Hs), agtra_mouse (Mm), agtrb_mouse (Mm), agtrb_rat (Rn), agtra_rat (Rn)
Other databases
Alphafold P30556 (Hs), P29755 (Mm), P29754 (Mm), P29089 (Rn), P25095 (Rn)
ChEMBL Target CHEMBL227 (Hs), CHEMBL5741 (Mm), CHEMBL263 (Rn), CHEMBL329 (Rn)
DrugBank Target P30556 (Hs)
Ensembl Gene ENSG00000144891 (Hs), ENSMUSG00000054988 (Mm), ENSMUSG00000049115 (Mm), ENSRNOG00000010640 (Rn), ENSRNOG00000018346 (Rn)
Entrez Gene 185 (Hs), 11607 (Mm), 11608 (Mm), 24180 (Rn), 81638 (Rn)
Human Protein Atlas ENSG00000144891 (Hs)
KEGG Gene hsa:185 (Hs), mmu:11607 (Mm), mmu:11608 (Mm), rno:24180 (Rn), rno:81638 (Rn)
OMIM 106165 (Hs)
Orphanet ORPHA138533 (Hs)
Pharos P30556 (Hs)
RefSeq Nucleotide NM_000685 (Hs), NM_175086 (Mm), NM_177322 (Mm), NM_030985 (Rn), NM_031009 (Rn)
RefSeq Protein NP_000676 (Hs), NP_796296 (Mm), NP_780295 (Mm), NP_112247 (Rn), NP_112271 (Rn)
UniProtKB P30556 (Hs), P29755 (Mm), P29754 (Mm), P29089 (Rn), P25095 (Rn)
Wikipedia AGTR1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the Angiotensin receptor revealed by serial femtosecond crystallography.
PDB Id:  4YAY
Ligand:  ZD-7155
Resolution:  2.9Å
Species:  Human
References:  187
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Human Angiotensin Receptor in Complex with Inverse Agonist Olmesartan at 2.8A resolution.
PDB Id:  4ZUD
Ligand:  olmesartan
Resolution:  2.8Å
Species:  Human
References:  186
Image of receptor 3D structure from RCSB PDB
Description:  Structure of synthetic nanobody-stabilized angiotensin II type 1 receptor bound to angiotensin II.
PDB Id:  6OS0
Ligand:  angiotensin II   This ligand is endogenous
Resolution:  2.9Å
Species:  Human
References:  171
Image of receptor 3D structure from RCSB PDB
Description:  Structure of synthetic nanobody-stabilized angiotensin II type 1 receptor bound to TRV023
PDB Id:  6OS1
Ligand:  TRV023
Resolution:  2.79Å
Species:  Human
References:  170
Image of receptor 3D structure from RCSB PDB
Description:  Structure of synthetic nanobody-stabilized angiotensin II type 1 receptor bound to TRV026
PDB Id:  6OS2
Ligand:  TRV026
Resolution:  2.7Å
Species:  Human
References:  170
Natural/Endogenous Ligands Click here for help
angiotensin A {Sp: Human}
angiotensin II {Sp: Human, Mouse, Rat}
angiotensin III {Sp: Human, Mouse, Rat}
angiotensin IV {Sp: Human, Mouse, Rat}

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I][Sar1]Ang-II Peptide Ligand is labelled Ligand is radioactive Rn Full agonist 9.5 pKd 42
⤷ pKd 9.5 (Kd 3.3x10-10 M) [42]
[125I][Sar1,Ile8]Ang-II Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Rn Partial agonist 9.4 pKd 42
⤷ pKd 9.4 (Kd 3.7x10-10 M) [42]
[Sar1,Cha8]Ang-II Peptide Rn Partial agonist 9.3 pKd 61,109
⤷ pKd 9.3 (Kd 4.7x10-10 M) [61,109]
[Sar1,Cha4]Ang-II Peptide Rn Agonist 7.1 pKd 61,109
⤷ pKd 7.1 (Kd 7.59x10-8 M) [61,109]
angiotensin A {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.8 pKi 177
⤷ pKi 8.8 IP accumulation in hAT1 expressing CHO cells [177]
TRV023 Peptide Hs Biased agonist 8.6 pKi 170
⤷ pKi 8.6 [170]
Description: Receptor binding
TRV026 Peptide Hs Biased agonist 8.3 pKi 170
⤷ pKi 8.3 [170]
Description: Receptor binding
[Sar1,Ile8]Ang-II Peptide Rn Partial agonist 8.8 pEC50 118
⤷ pEC50 8.8 (EC50 1.5x10-9 M) [118]
angiotensin A {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.2 pEC50 177
⤷ pEC50 8.2 IP accumulation in hAT1 expressing CHO cells [177]
angiotensin IV {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Hs Partial agonist 5.9 pEC50 90
⤷ pEC50 5.9 [90]
TRV023 Peptide Hs Biased agonist 5.7 pEC50 175
⤷ pEC50 5.7 (EC50 2.1x10-6 M) [175]
Description: β-arrestin recruitment assay
angiotensin A {Sp: Human} Peptide Ligand is endogenous in the given species Rn Partial agonist 9.5 pIC50 71
⤷ pIC50 9.5 calcium release in rat VSMC [71]
angiotensin II {Sp: Human, Mouse, Rat} Peptide Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 9.0 – 9.3 pIC50 35,160
⤷ pIC50 9.0 – 9.3 [35,160]
angiotensin III {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.4 – 8.5 pIC50 35
⤷ pIC50 8.4 – 8.5 [35]
L-163,101 Small molecule or natural product Hs Agonist 7.9 pIC50 159
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [159]
L-162,313 Small molecule or natural product Hs Full agonist 7.8 – 7.9 pIC50 126
⤷ pIC50 7.8 – 7.9 (IC50 1.42x10-8 – 1.19x10-8 M) [126]
View species-specific agonist tables
Agonist Comments
Ind8-AngII, a modified version of AngII which was generated by the addition of a single connecting methylene group to the terminal phenyl moiety, produces an AT1R β-arrestin biased ligand (human receptor Ki 38 nM) [147],
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
5-butyl-methyl immidazole carboxylate 30 Small molecule or natural product Hs Antagonist 7.8 pA2 3
⤷ pA2 7.8 [3]
[3H]candesartan Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 10.3 pKd 44
⤷ pKd 10.3 [44]
[Sar1,Ile8]Ang-II Peptide Hs Antagonist 9.4 pKd 61
⤷ pKd 9.4 (Kd 3.7x10-10 M) [61]
[3H]A81988 Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.2 pKd 51
⤷ pKd 9.2 (Kd 5.7x10-10 M) [51]
[3H]L158809 Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.2 pKd 23
⤷ pKd 9.2 (Kd 6.6x10-10 M) [23]
[3H]eprosartan Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.1 pKd 6
⤷ pKd 9.1 (Kd 8.3x10-10 M) [6]
[Sar1,Ala8]Ang-II Peptide Hs Antagonist 9.1 pKd 61
⤷ pKd 9.1 (Kd 9x10-10 M) [61]
[125I]EXP985 Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 8.8 pKd 24
⤷ pKd 8.8 (Kd 1.49x10-9 M) [24]
[3H]irbesartan Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.7 pKd 161
⤷ pKd 8.7 [161]
[3H]losartan Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Antagonist 8.2 pKd 19
⤷ pKd 8.2 (Kd 6.2x10-9 M) [19]
TRV027 Peptide Hs Antagonist 7.7 pKd 164
⤷ pKd 7.7 (Kd 1.9x10-8 M) [164]
[Sar1,Ile4,Ile8]Ang-II Peptide Hs Antagonist 6.5 pKd 168
⤷ pKd 6.5 (Kd 3.1x10-7 M) [168]
[Sar1,Gly4,Gly8]Ang-II Peptide Hs Antagonist 6.5 pKd 61
⤷ pKd 6.5 (Kd 3.1x10-7 M) [61]
saprisartan Small molecule or natural product Rn Antagonist 9.1 pKi 57
⤷ pKi 9.1 [57]
sparsentan Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.1 pKi 110
⤷ pKi 9.1 (Ki 8x10-10 M) [110]
5-oxo-1-2-4-oxadiazol biphenyl Small molecule or natural product Rn Antagonist 9.0 pKi 117
⤷ pKi 9.0 (Ki 1.03x10-9 M) [117]
compound 2 [PMID: 28379944] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.4 pKi 185
⤷ pKi 8.4 (Ki 3.7x10-9 M) [185]
compound 1 [PMID: 28379944] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.7 pKi 185
⤷ pKi 6.7 (Ki 1.8x10-7 M) [185]
candesartan Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 9.5 – 9.7 pIC50 160
⤷ pIC50 9.5 – 9.7 (IC50 3.2x10-10 – 1.9x10-10 M) [160]
tasosartan Small molecule or natural product Hs Antagonist 8.9 pIC50 97
⤷ pIC50 8.9 (IC50 1.2x10-9 M) [97]
[3H]valsartan Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Antagonist 8.8 – 9.0 pIC50 163
⤷ pIC50 8.8 – 9.0 (IC50 1.58x10-9 – 1x10-9 M) [163]
5-oxo-1-2-4-oxadiazol biphenyl Small molecule or natural product Rn Antagonist 8.8 pIC50 117
⤷ pIC50 8.8 (IC50 1.6x10-9 M) [117]
irbesartan Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.7 – 8.8 pIC50 160
⤷ pIC50 8.7 – 8.8 (IC50 1.99x10-9 – 1.58x10-9 M) [160]
valsartan Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Antagonist 8.6 pIC50 34
⤷ pIC50 8.6 (IC50 2.43x10-9 M) [34]
eprosartan Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 8.4 – 8.8 pIC50 38
⤷ pIC50 8.4 – 8.8 (IC50 3.98x10-9 – 1.58x10-9 M) [38]
5-butyl-methyl immidazole carboxylate 30 Small molecule or natural product Hs Antagonist 8.5 pIC50 3
⤷ pIC50 8.5 [3]
EXP3174 Small molecule or natural product Hs Antagonist 7.4 – 9.5 pIC50 152,160
⤷ pIC50 7.4 – 9.5 (IC50 3.98x10-8 – 3.2x10-10 M) [152,160]
ZD-7155 Small molecule or natural product Ligand has a PDB structure Cp Antagonist 8.4 pIC50 169
⤷ pIC50 8.4 (IC50 3.8x10-9 M) [169]
telmisartan Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Antagonist 8.4 pIC50 105
⤷ pIC50 8.4 [105]
forasartan Small molecule or natural product Approved drug Rn Antagonist 8.2 – 8.6 pIC50 122
⤷ pIC50 8.2 – 8.6 (IC50 6.9x10-9 – 2.8x10-9 M) [122]
LY303336 Small molecule or natural product Hs Antagonist 8.3 pIC50 162
⤷ pIC50 8.3 [162]
LY301875 Small molecule or natural product Hs Antagonist 8.2 pIC50 162
⤷ pIC50 8.2 [162]
azilsartan Small molecule or natural product Hs Antagonist 8.1 – 8.1 pIC50 130,148
⤷ pIC50 8.1 – 8.1 (IC50 8.4x10-9 – 7.4x10-9 M) [130,148]
olmesartan Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 8.1 pIC50 79
⤷ pIC50 8.1 [79]
N,N`-bis-alkyl butylimmidazole 12b Small molecule or natural product Hs Antagonist 8.1 pIC50 4
⤷ pIC50 8.1 (IC50 8.5x10-9 M) [4]
losartan Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Antagonist 7.4 – 8.7 pIC50 35,152
⤷ pIC50 7.4 – 8.7 (IC50 3.98x10-8 – 1.99x10-9 M) [35,152]
View species-specific antagonist tables
Antagonist Comments
LY301875, LY303336, telmisartan, candesartan, irbesartan, valsartan, EXP3174, azilsartan medoxomil and saprisartan [150-151] are all classed as insurmountable antagonists.

Partial agonist: Activate the receptor but have only partial efficacy (less than 50%) at the receptor relative to a full agonist.

Insurmountable antagonists: When preincubated on cells/tissues these competitive antagonists cause a full or partial depression of the maximal response induced by an agonist (e.g. Angiotensin II) in a concentration-response curve. The degree of insurmountable inhibition is related to the formation of a slow dissociating receptor-antagonist complex [45,105,160,162-163].

Selective ligands ([Sar1,Ile4,Ile8]Ang II, [Sar1-Ala8]-Ang II, [Sar1-Ile8]-Ang II, [Sar1-Gly4,Gly8]-Ang II and TRV120027): Produce greater than 80% activation of G-protein-independent signal and less than 20% activation of G-protein-dependent signal. For an overview of AT1R antagonist binding properties see [107].

Two losartan derivatives have been developed for positron emission tomography (PET): [18F]FEtLos (Ki = 2000 nM) and [18F]AMBF3Los (Ki = 7.9 nM) [137].
Immunopharmacology Comments
Accumulating evidence suggests that regulation of the mutually antagonistic angiotensin receptors AT1 and AT2 is essential for maintaining control of inflammation and that an imbalance between these two receptors has pathophysiological potential [145].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family
Gq/G11 family 		Adenylyl cyclase inhibition
Phospholipase C stimulation
Calcium channel
Phospholipase A2 stimulation
Phospholipase D stimulation
Other - See Comments
Comments:  Other effectors and responses are inositol phosphate turnover, protein kinase C activation and RhoA activation. Other transducers are JAK2 resulting in STAT3 phosphorylation [99].; Src with effectors FAK, GIT1, CamK II, Cas [115,124]; pp60c-src with effector phospholipase C-gamma 1 [65,100]; β-arrestin resulting in MAPK phosphorylation in the cytoplasm; and CARMA3 with effector NF-κB [104].

Like many growth factors, activation of several tyrosine kinases (receptor (EGFR), non-receptor (JAK, Src, Pyk2)) and phosphorylation and activation of several downstream cascades such as mitogen activated protein (MAP kinase) cascade, the JAK-STAT pathway are observed. AT1R activation also lead to ROS production via activation of the NADH-NADPH oxidase pathways, modulation of ion channels, transactivation of EGFR [13,33,36,50,141-142,155,176]. G-protein dependent signalling leads to phosphorylation and nuclear translocation of Elk-1 and MAPK whereas β-arrestin dependent signalling leads to MAPK phosphorylation in the cytoplasm [5,154] but not nuclear translocation.
References:  33
Tissue Distribution Click here for help
Liver, kidney, adrenal, lung >heart, thymus, uterus, ovary, aorta, colon, eye, lymphocyte, macrophage, mammary gland, mucous gland, muscle, nervous system, pituitary gland, placenta, spleen, testis.
Species:  Human
Technique:  Northern blotting.
References:  7,16,26-27,33,102-103,149
The overall amino acid sequence homology is greater than 92% in rat and mouse. The AT1A is mainly located on vascular smooth muscle cells, lung, liver, brain, kidney, heart, whereas the AT1B is predominantly detected in adrenal and pituitary glands. AT1A and AT1B differ in their 5'- and 3'-untranslated regions and are distinct in their regulation.
Species:  Rat
Technique:  Not specified
References:  33
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Ang II-induced aldosterone release
Species:  Human
Tissue:  Bovine adrenal glomerulosa cells
Response measured:  Aldosterone release
References:  25
AngII-induced histone code alteration
Species:  Human
Tissue:  HEK293 cells, HASMCs, HL1 cells
Response measured:  Histone H2A posttranslational modifications
References:  70
AngII-induced histone code alteration
Species:  Mouse
Tissue:  HEK293 cells, HASMCs, HL1 cells
Response measured:  Histone H2A posttranslational modifications
References:  70
Second messenger response
Species:  None
Tissue:  COS-1 and HEK293 cells
Response measured:  Inositol Phosphate, Calcium response, ERK activation
References:  14,42,118,157-158
Na+ transport
Species:  Rat
Tissue:  Kidney
Response measured: 
References:  52
Fractional shortening
Species:  Mouse
Tissue:  Endothelial cells
Response measured:  ΔP/Δt
References:  131
IL17 production
Species:  Mouse
Tissue:  Smooth muscle cells, T cells
Response measured: 
References:  96
AngII-induced Gβγ translocation to nucleus
Species:  Human
Tissue:  Human aortic smooth muscle cells
Response measured:  Gβγ translocation to nucleus, MEF2A transcriptional activity, HDAC5 regulation
References:  14
AngII-induced Gβgamma; translocation to nucleus
Species:  Rat
Tissue:  Neonatal ventricular myocytes
Response measured:  Gβγ translocation to nucleus, MEF2A transcriptional activity, HDAC5 regulation
References:  14
AngII-induced Gβγ translocation to nucleus
Species:  Mouse
Tissue:  Adult ventricualar myocytes
Response measured:  Gβγ translocation to nucleus, MEF2A transcriptional activity, HDAC5 regulation
References:  14
AngII-induced STAT3 expression
Species:  Human
Tissue:  HEK293 cells, neonatal cardiac myocytes and fibroblasts
Response measured:  Unphosphorylated STAT3 accumulation in the nucleus
References:  182
AngII-induced STAT3 expression
Species:  Mouse
Tissue:  HEK293 cells neonatal cardiac myocytes and fibroblasts
Response measured:  Unphosphorylated STAT3 accumulation in the nucleus
References:  182
Physiological Functions Click here for help
Renal secretion
Species:  Mouse
Tissue: 
References:  98
Smooth muscle cell contraction, proliferation and migration
Species:  Human
Tissue:  Not specified
References:  10,62,78,108,127,155,184
Central and peripheral sympathetic stimulation
Species:  Rat
Tissue:  Heart
References:  120,144
Aldosterone release
Species:  Human
Tissue:  Bovine glomerulosa cell
References:  25
ADH release
Species:  Human
Tissue:  Ang III > Ang II
References:  129,132
Endothelin release
Species:  Human
Tissue:  Endothelial cells
References:  43,123,143,146
Tubular sodium reabsorption
Species:  Human
Tissue:  Not specified
References:  17,84,116
Extracellular matrix formation and fibrotic deposition
Species:  Human
Tissue:  Not specified
References:  41,91,136,155
Regulation of systemic arterial blood pressure
Species:  Human
Tissue: 
References:  103
Acetyltransferase activator activity
Species:  Human
Tissue: 
References:  75
Regulation of cell growth
Species:  Human
Tissue: 
References:  55
Kidney development
Species:  Human
Tissue: 
References:  98,156
Kidney development
Species:  Human
Tissue: 
References:  49
Positive regulation of cellular protein metabolic process
Species:  Human
Tissue: 
References:  75
Smooth muscle cell contraction, proliferation and migration
Species:  Rat
Tissue: 
References:  86
Smooth muscle cell contraction, proliferation and migration
Species:  Mouse
Tissue: 
References:  111
Aldosterone release
Species:  Mouse
Tissue: 
References:  98
Aldosterone release
Species:  Rat
Tissue: 
References:  76
Regulation of blood vessel size and development
Species:  Human
Tissue: 
References:  2
Regulation of blood vessel size and development
Species:  Mouse
Tissue: 
References:  156
Regulation of vasoconstriction
Species:  Rat
Tissue: 
References:  29
Regulation of vasoconstriction
Species:  Human
Tissue: 
References:  11,55,103
Cell chemotaxis
Species:  Human
Tissue: 
References:  55
Regulation of smooth muscle cell apoptotic process
Species:  Mouse
Tissue: 
References:  111
Drinking behaviour
Species:  Mouse
Tissue: 
References:  31,98
Regulation of systemic arterial blood pressure
Species:  Rat
Tissue: 
References:  119,165
Regulation of systemic arterial blood pressure
Species:  Mouse
Tissue: 
References:  8,60,156
Positive regulation of macrophage derived foam cell differentiation
Species:  Human
Tissue: 
References:  75
Positive regulation of cholesterol esterification
Species:  Human
Tissue: 
References:  75
Positive regulation of NAD(P)H oxidase activity
Species:  Human
Tissue: 
References:  55
Low-density lipoprotein particle remodeling
Species:  Human
Tissue: 
References:  95
Regulation of inflammatory response
Species:  Mouse
Tissue: 
References:  40
Regulation of inflammatory response
Species:  Human
Tissue: 
References:  103
Positive regulation of reactive oxygen species metabolic process
Species:  Human
Tissue: 
References:  55
Augmentation of peripheral noradrenergic activity, decreased renal blood flow, renal renin inhibition, cardiac contractility, central osmocontrol
Species:  Human
Tissue: 
References:  18
Positive regulation of reactive oxygen species metabolic process
Species:  Human
Tissue: 
References:  55
Positive regulation of reactive oxygen species metabolic process
Species:  Rat
Tissue: 
References:  112
Heart development
Species:  Mouse
Tissue: 
References:  66
Positive regulation of cytokine secretion
Species:  Mouse
Tissue: 
References:  69
Regulation of pH
Species:  Rat
Tissue: 
References:  121
Aging
Species:  Rat
Tissue: 
References:  76
Dopamine biosynthetic process
Species:  Rat
Tissue: 
References:  106
Response to estrogen stimulus
Species:  Rat
Tissue: 
References:  9,172
Physiological Consequences of Altering Gene Expression Click here for help
AGTR1 overexpression due to increased copy number is linked to breast cancer and oesophageal cancer (Rhodes et al. , 2009, Chen et al., 2008). A1166C gene polymorphism is more frequent in hypertensive patients. There is a greater decreased of left ventricular mass, collagen synthesis in AA after AT1 receptor blockade than after beta-blockade. There is an increased cardiovascular risk in CC, independent of blood pressure. Several polymorphisms in the promoter region of AT1 gene were reported among which A-810T and A-153G polymorphisms might be a genetic risk factor for the pathogenesis of coronary heart disease complicated with essential hypertension in Chinese Han population (Jin et al., 2003, Zhang et al., 2009).
Species:  Human
Tissue: 
Technique:  Not specified
References:  15,22,37,72-73,81,133,167
Physiological Consequences of Altering Gene Expression Comments
Mice lacking the AT1a receptor have a marked reduction of systolic blood pressure [178]. There is no impairment of development and no major abnormalities of the heart and vascular system in AT1A KO mice but there are mild signs of mesangial expansion and juxtaglomerular cell hypertrophy. The tubuloglomerular feedback loop is undetectable. The lack of AT1a signaling causes structural abnormalities in the renal vascular system and transforms the phenotype of VSMCs into cell proliferation, induces the escape of VSMCs from the circular mechanical integrity, and results in increased synthesis of extracellular matrices [64]. AT1a receptor knockout mice display less left ventricular remodeling and improved survival after myocardial infarction [53]. Deficiency of angiotensin type 1a receptors in adipocytes reduces differentiation and promotes hypertrophy of adipocytes in lean mice [128]. AngII can elicit renal vasoconstriction, albeit attenuated, in AT1A knockout mice [135]. Ischemia-induced angiogenesis was also impaired in in AT1a receptor knockout mice suggesting that AT1 receptor pathway promotes early angiogenesis by supporting inflammatory cell infiltration and angiogenic cytokine expression [139]. Genetic disruption of AT1a receptor improves long-term survival of mice with chronic severe aortic regurgitation (AR). In cases of chronic severe AR, blockade of AT1 receptor attenuates the progression of LV dilatation, hypertrophy and fibrosis, thereby mitigating heart failure and improving long-term survival [114]. AT1a receptor knockout in mice causes polyuria and urine concentration defects by reducing basal vasopressin levels and its receptor signaling proteins in the inner medulla [94]. AT1a receptor deficient mice exhibited reduced angiogenesis and delay in wound healing in angiotensin II type 1a receptor- [83]. AT1a receptor plays an important role in skin wound healing by accelerating keratinocyte and fibroblast migration via heparin-binding epidermal growth factor (EGF)-like growth factor-mediated EGF receptor transactivation [174]. Expression of AT1a receptors in C1 neurons restores the sympathoexcitation to angiotensin in the rostral ventrolateral medulla of AT1a knockout mice [21]. Mice lacking the AT1B receptor do not differ from wild-type. The AT1B receptor has a minor role but may compensate for much of the regulatory action in AT1A deleted rodent. For example, AT1B receptor mediates calcium signaling in vascular smooth muscle cells of AT1A receptor-deficient mice [188]. Animals with both AT1A and AT1B gene deletion have an impaired growth, hypotension and marked abnormalities in renal structures. There is a complete absence of pressor responses to Ang II. Transgenic mice overexpressing the AT1 receptor exhibit a drastic cardiac hypertrophy and die within several days of age. The transgenic rats however appear normal unless there is pressure or volume overload, which elicit a more pronounced hypertrophy than in normal rats. Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling with increased expression of ventricular atrial natriuretic factor and interstitial collagen deposition and died prematurely of heart failure. Neither the systolic blood pressure nor the heart rate were changed [125]. AT1R overexpression in the mouse myocardium produces a lethal phenotype associated with myocyte hyperplasia and heart block [54]. Increased expression of cardiac AT1a receptors decreases myocardial microvessel density after experimental myocardial infarction and this is amenable to AT(1) receptor blockade, suggesting that efficacy of AT1 receptor blockers post-myocardial infarction may be due to a stimulatory effect on angiogenesis [32]. Overexpression of AT1a receptors impairs excitation-contraction coupling in the mouse heart before the development of cardiac hypertrophy [134]. Overexpression of AT(1) receptor under the control of alpha-myosin heavy chain promoter in angiotensinogen-knockout background mice showed spontaneous systolic dysfunction and chamber dilatation, accompanied by severe interstitial fibrosis. Progression of cardiac remodeling in this model was prevented by treatment with candesartan, an inverse agonist for the AT(1) receptor demonstrating that constitutive activity of the AT(1) receptor under basal conditions contributes to the cardiac remodeling even in the absence of Ang II, when the AT(1) receptor is upregulated in the heart [179]. Transgenic rat model that exhibits an upregulated myocardial AT1 receptor density demonstrates augmented cardiac hypertrophy and contractile response to angiotensin II after volume and pressure overload, but not under baseline conditions [58]. Brain-selective overexpression of AT1a receptors resulted in enhanced cardiovascular responsiveness to intracerebroventricular (ICV) Ang II injection with no change in baseline blood. However, blockade of central AT1 receptors with ICV losartan reduced basal blood pressure suggesting an enhanced contribution of central AT1 receptors to the maintenance of baseline blood pressure in this model [87]. Renovascular hypertension in mice with brain-selective overexpression of AT1a receptors is buffered by increased nitric oxide production in the periphery suggesting that activation of endogenous NO systems plays an important role in buffering the maintenance of hypertension caused by overexpression of AT(1a) receptors in the brain [88]. Brain-selective overexpression of AT(1A) receptors results in enhanced salt appetite and altered water intake [89]. AT1 receptor overexpression in podocytes induces protein leakage and structural podocyte damage progressing to focal segmental glomerulosclerosis in transgenic rats [59]. Mice with overexpression of a constitutively active AT1a receptor transgene in renal proximal tubule caused increased baseline blood pressure. Depletion of endogenous AT1a receptors in the proximal tubule reduced blood pressure. In contrast to the changes observed at baseline, there was no difference in the blood pressure response to a pressor dose of Ang II in either experimental model suggesting that Ang II signaling via the AT1a receptor in the renal proximal tubule is a regulator of systemic blood pressure under baseline conditions [93].
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd		 MGI:87964  MP:0000818 abnormal amygdala morphology PMID: 11384784 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0009642 abnormal blood homeostasis PMID: 17607364 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0001544 abnormal cardiovascular system physiology PMID: 17607364 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0005416 abnormal circulating protein level PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0005416 abnormal circulating protein level PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0005416 abnormal circulating protein level PMID: 18497303 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0003921 abnormal heart left ventricle morphology PMID: 17607364 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0001629 abnormal heart rate PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0001629 abnormal heart rate PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0001629 abnormal heart rate PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0001629 abnormal heart rate PMID: 18497303 
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0001629 abnormal heart rate PMID: 18497303 
Agtr1atm1Tma Agtr1atm1Tma/Agtr1atm1Tma
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0002829 abnormal juxtaglomerular apparatus PMID: 8878439 
Agtr1atm2Tma Agtr1atm2Tma/Agtr1atm2Tma
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0002829 abnormal juxtaglomerular apparatus PMID: 8878439 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0004195 abnormal kidney calyx morphology PMID: 9466969 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0000527 abnormal kidney development PMID: 9466969 
Agtr1atm1Afu Agtr1atm1Afu/Agtr1atm1Afu
involves: C57BL/6 * CBA		 MGI:87964  MP:0002135 abnormal kidney morphology PMID: 11292619 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0002135 abnormal kidney morphology PMID: 18497303 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0004193 abnormal kidney papilla morphology PMID: 9466969 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0004194 abnormal kidney pelvis morphology PMID: 10432390 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0002136 abnormal kidney physiology PMID: 17607364 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0000530 abnormal kidney vasculature morphology PMID: 10432390  9466969 
Agtr1atm1Tma Agtr1atm1Tma/Agtr1atm1Tma
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0000530 abnormal kidney vasculature morphology PMID: 8878439 
Agtr1atm2Tma Agtr1atm2Tma/Agtr1atm2Tma
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0000530 abnormal kidney vasculature morphology PMID: 8878439 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0000530 abnormal kidney vasculature morphology PMID: 17607364 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0008872 abnormal physiological response to xenobiotic PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0008872 abnormal physiological response to xenobiotic PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0008872 abnormal physiological response to xenobiotic PMID: 18497303 
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0008872 abnormal physiological response to xenobiotic PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0005325 abnormal renal glomerulus morphology PMID: 18497303 
Agtr1btm1Cof|Agtr2tm1Tin Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87965  MGI:87966  MP:0005325 abnormal renal glomerulus morphology PMID: 18497303 
Agtr1btm1Cof|Agtr2tm1Tin Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87965  MGI:87966  MP:0005325 abnormal renal glomerulus morphology PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0005325 abnormal renal glomerulus morphology PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0005325 abnormal renal glomerulus morphology PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 18497303 
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 18497303 
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd * C57BL/6J		 MGI:87964  MP:0000230 abnormal systemic arterial blood pressure PMID: 7724593 
Agtr1a+|Agtr1atm1Unc Agtr1atm1Unc/Agtr1a+
involves: 129P2/OlaHsd * C57BL/6J		 MGI:87964  MP:0000230 abnormal systemic arterial blood pressure PMID: 7724593 
Agtr1atm1Afu|Agtr2tm1Gsb Agtr1atm1Afu/Agtr1atm1Afu,Agtr2tm1Gsb/Y
mixed		 MGI:87964  MGI:87966  MP:0000230 abnormal systemic arterial blood pressure PMID: 12388241 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0000230 abnormal systemic arterial blood pressure PMID: 9466969 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0000230 abnormal systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0000230 abnormal systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0000230 abnormal systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0000230 abnormal systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0000230 abnormal systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0000230 abnormal systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd		 MGI:87964  MP:0000832 abnormal thalamus morphology PMID: 11384784 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0003141 cardiac fibrosis PMID: 17607364 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0005608 cardiac interstitial fibrosis PMID: 17607364 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0001262 decreased body weight PMID: 17607364 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0001262 decreased body weight PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0001262 decreased body weight PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0001262 decreased body weight PMID: 18497303 
Agtr1btm1Cof|Agtr2tm1Tin Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87965  MGI:87966  MP:0001262 decreased body weight PMID: 18497303 
Agtr1btm1Cof|Agtr2tm1Tin Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87965  MGI:87966  MP:0001262 decreased body weight PMID: 18497303 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0006376 decreased circulating angiotensinogen level PMID: 17607364 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0003353 decreased circulating renin level PMID: 17607364 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0005558 decreased creatinine clearance PMID: 17607364 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0005333 decreased heart rate PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0005333 decreased heart rate PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0005333 decreased heart rate PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0005333 decreased heart rate PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0005333 decreased heart rate PMID: 18497303 
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0005333 decreased heart rate PMID: 18497303 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0002834 decreased heart weight PMID: 9466969 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0002834 decreased heart weight PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0002834 decreased heart weight PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0002834 decreased heart weight PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0002834 decreased heart weight PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0002834 decreased heart weight PMID: 18497303 
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0002834 decreased heart weight PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0003918 decreased kidney weight PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0003918 decreased kidney weight PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0003918 decreased kidney weight PMID: 18497303 
Agtr1btm1Cof|Agtr2tm1Tin Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87965  MGI:87966  MP:0003918 decreased kidney weight PMID: 18497303 
Agtr1btm1Cof|Agtr2tm1Tin Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87965  MGI:87966  MP:0003918 decreased kidney weight PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0003918 decreased kidney weight PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0003918 decreased kidney weight PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0004876 decreased mean systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0004876 decreased mean systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0004876 decreased mean systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0004876 decreased mean systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Unc|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87966  MP:0004876 decreased mean systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0004876 decreased mean systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 17607364 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0005618 decreased potassium excretion PMID: 17607364 
Agtr1atm1Unc|Agtr1btm1Cof|Hprttm1(Ggt1-Agtr1)Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Hprttm1(Ggt1-Agtr1)Cof/Y
involves: 129P2/OlaHsd		 MGI:87964  MGI:87965  MGI:96217  MP:0005583 decreased renin activity PMID: 15306694 
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd * C57BL/6J		 MGI:87964  MP:0002843 decreased systemic arterial blood pressure PMID: 7724593 
Agtr1a+|Agtr1atm1Unc Agtr1atm1Unc/Agtr1a+
involves: 129P2/OlaHsd * C57BL/6J		 MGI:87964  MP:0002843 decreased systemic arterial blood pressure PMID: 7724593 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0002843 decreased systemic arterial blood pressure PMID: 9466969 
Agtr1atm1Afu Agtr1atm1Afu/Agtr1atm1Afu
involves: C57BL/6 * CBA * ICR		 MGI:87964  MP:0006264 decreased systemic arterial systolic blood pressure PMID: 12388241  7642517 
Agtr1a+|Agtr1atm1Afu Agtr1atm1Afu/Agtr1a+
involves: C57BL/6 * CBA * ICR		 MGI:87964  MP:0006264 decreased systemic arterial systolic blood pressure PMID: 7642517 
Agtr1atm1Unc Agtr1atm1Unc/Agtr1atm1Unc
involves: 129P2/OlaHsd * C57BL/6J		 MGI:87964  MP:0006264 decreased systemic arterial systolic blood pressure PMID: 7724593 
Agtr1a+|Agtr1atm1Unc Agtr1atm1Unc/Agtr1a+
involves: 129P2/OlaHsd * C57BL/6J		 MGI:87964  MP:0006264 decreased systemic arterial systolic blood pressure PMID: 7724593 
Agtr1atm1Unc|Hprttm1(Ggt1-Agtr1)Cof Agtr1atm1Unc/Agtr1atm1Unc,Hprttm1(Ggt1-Agtr1)Cof/Y
involves: 129P2/OlaHsd		 MGI:87964  MGI:96217  MP:0002988 decreased urine osmolality PMID: 15306694 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0003620 decreased urine output PMID: 17607364 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0003670 dilated renal glomerular capsule PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0002705 dilated renal tubules PMID: 18497303 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0002593 high mean erythrocyte cell number PMID: 17607364 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0000519 hydronephrosis PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0000519 hydronephrosis PMID: 18497303 
Agtr1atm1Afu Agtr1atm1Afu/Agtr1atm1Afu
involves: C57BL/6 * CBA		 MGI:87964  MP:0001596 hypotension PMID: 15087458 
Agtr1atm1Unc|Hprttm1(Ggt1-Agtr1)Cof Agtr1atm1Unc/Agtr1atm1Unc,Hprttm1(Ggt1-Agtr1)Cof/Y
involves: 129P2/OlaHsd		 MGI:87964  MGI:96217  MP:0001596 hypotension PMID: 15306694 
Agtr1atm1Afu Agtr1atm1Afu/Agtr1atm1Afu
involves: C57BL/6 * CBA * ICR		 MGI:87964  MP:0001596 hypotension PMID: 7642517 
Agtr1a+|Agtr1atm1Afu Agtr1atm1Afu/Agtr1a+
involves: C57BL/6 * CBA * ICR		 MGI:87964  MP:0001596 hypotension PMID: 7642517 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0005565 increased blood urea nitrogen level PMID: 17607364 
Agtr1atm1Afu Agtr1atm1Afu/Agtr1atm1Afu
involves: C57BL/6 * CBA * ICR		 MGI:87964  MP:0003352 increased circulating renin level PMID: 7642517 
Agtr1atm1Afu Agtr1atm1Afu/Agtr1atm1Afu
involves: C57BL/6 * CBA * ICR		 MGI:87964  MP:0003911 increased drinking behavior PMID: 12388241 
Agtr1atm1Afu|Agtr2tm1Gsb Agtr1atm1Afu/Agtr1atm1Afu,Agtr2tm1Gsb/Y
mixed		 MGI:87964  MGI:87966  MP:0003911 increased drinking behavior PMID: 12388241 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0002833 increased heart weight PMID: 17607364 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0005564 increased hemoglobin content PMID: 17607364 
Agtr1btm1Cof|Agtr2tm1Tin Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87965  MGI:87966  MP:0004875 increased mean systemic arterial blood pressure PMID: 18497303 
Agtr1btm1Cof|Agtr2tm1Tin Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87965  MGI:87966  MP:0004875 increased mean systemic arterial blood pressure PMID: 18497303 
Agtr1atm1Afu Agtr1atm1Afu/Agtr1atm1Afu
involves: C57BL/6 * CBA * ICR		 MGI:87964  MP:0005582 increased renin activity PMID: 7642517 
Agtr1atm1Tma Agtr1atm1Tma/Agtr1atm1Tma
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MP:0002842 increased systemic arterial blood pressure PMID: 9466969 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0006144 increased systemic arterial systolic blood pressure PMID: 17607364 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0008055 increased urine osmolality PMID: 17607364 
Agtr1atm1Unc|Agtr1btm1Cof|Hprttm1(Ggt1-Agtr1)Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Hprttm1(Ggt1-Agtr1)Cof/Y
involves: 129P2/OlaHsd		 MGI:87964  MGI:87965  MGI:96217  MP:0003675 kidney cysts PMID: 15306694 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0003675 kidney cysts PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0001859 kidney inflammation PMID: 18497303 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0010420 muscular ventricular septal defect PMID: 9466969 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0010418 perimembraneous ventricular septal defect PMID: 9466969 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0002082 postnatal lethality PMID: 9466969 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Agtr2tm1Tin
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0002082 postnatal lethality PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof|Agtr2tm1Tin Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof,Agtr2tm1Tin/Y
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MGI:87966  MP:0002082 postnatal lethality PMID: 18497303 
Agtr1atm1Unc|Agtr1btm1Cof Agtr1atm1Unc/Agtr1atm1Unc,Agtr1btm1Cof/Agtr1btm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0002082 postnatal lethality PMID: 18497303 
Agtr1atm1Ecl Agtr1atm1Ecl/Agtr1atm1Ecl
involves: 129S2/SvPas * C57BL/6		 MGI:87964  MP:0003985 renal fibrosis PMID: 17607364 
Agtr1atm1Tma|Agtr1btm1Ii Agtr1atm1Tma/Agtr1atm1Tma,Agtr1btm1Ii/Agtr1btm1Ii
involves: 129P2/OlaHsd * C57BL/6		 MGI:87964  MGI:87965  MP:0010402 ventricular septal defect PMID: 9466969 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Cardiac hypertrophy
References:  18,56
Disease:  Hypertension, essential
Disease Ontology: DOID:10825
OMIM: 145500
References:  15,77,167
Disease:  Renal tubular dysgenesis
OMIM: 267430
Orphanet: ORPHA97369
References:  49
Clinically-Relevant Mutations and Pathophysiology Comments
Other pathophysiological actions of AT1 receptor include induction of cardiac fibrosis, renal fibrosis, perivascular fibrosis, induction of cell and tissue senescence, induction of insulin resistance, induction of endothelial dysfunction, induction of skeletal muscle wasting, reduction of exercise tolerance, induction of tissue ER stress, induction of aortic aneurysm, acceleration of atherosclerosis. Preeclampsia is associated with the presence of autoantibodies capable of activating the AT1R [166,173]. AT(1)-B(2)-receptor heterodimerization is also reported to be correlated to preeclampsia [1].
Biologically Significant Variants Click here for help
Type:  Not specified
Species:  Human
Description:  Human tissues that express the angiotensin II (Ang II) type 1 receptor (hAT(1)R) can synthesize four distinct alternatively spliced hAT(1)R mRNA transcripts. A long AT1 receptor isoform has 3-fold reduced affinity for Ang II
References:  101
Type:  Not specified
Species:  Human
Description:  In contrast to rodents, the existence of various isoforms for the human AT1 receptor is not proven.
References:  48,80,82
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A 573C-T polymorphism of AGTR1 is associated with final height in women, and is one of several genes associated with stature as a quantitative trait as described by this OMIM entry.
Nucleotide change:  573C>T
References:  20
General Comments
For information on miRNAs predicted to target AGTR1 3'-UTR please see TargetScan [46,92].
Crystallography has confirmed the different conformations that AT1R adopts in Gq-biased and β-arrestin-biased ligand-bound states [147].
AT1R cross talk with TRPV4 has been observed. Internalization of both the receptors is inhibited by antagonists that independently target either partner in the interaction pair [183].

References

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