Gene and Protein Information
class A G protein-coupled receptor
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	7	349	9q33.2	GPR21	G protein-coupled receptor 21	1
Mouse	7	349	2 B	Gpr21	G protein-coupled receptor 21
Rat	7	349	3q11	Gpr21	G protein-coupled receptor 21

Database Links
Specialist databases
GPCRdb	gpr21_human (Hs), gpr21_mouse (Mm)
Other databases
Alphafold	Q99679 (Hs), Q8BX79 (Mm)
ChEMBL Target	CHEMBL4523913 (Hs)
Ensembl Gene	ENSG00000188394 (Hs), ENSMUSG00000053164 (Mm), ENSRNOG00000042269 (Rn)
Entrez Gene	2844 (Hs), 338346 (Mm), 311911 (Rn)
Human Protein Atlas	ENSG00000188394 (Hs)
KEGG Gene	hsa:2844 (Hs), mmu:338346 (Mm), rno:311911 (Rn)
OMIM	601909 (Hs)
Pharos	Q99679 (Hs)
RefSeq Nucleotide	NM_005294 (Hs), NM_177383 (Mm), NM_001109554 (Rn)
RefSeq Protein	NP_005285 (Hs), NP_796357 (Mm), NP_001103024 (Rn)
UniProtKB	Q99679 (Hs), Q8BX79 (Mm)
Wikipedia	GPR21 (Hs)

Primary Transduction Mechanisms
Comments:  GPR21 was reported to activate the Gq pathway based on its effect on calcium-sensitive CHO cells using a transcription-based reporter assay.
References:  1

Tissue Distribution
Brain (especially pre-optic area of the hypothalamus), adipose tissue, liver, bone marrow, spleen, macrophages Species:  Mouse Technique:  Quantitative real time PCR References:  2-3
Tissue Distribution Comments
GPR21 was isolated originally from the brain, but the transcripts of GPR21 gene were not detected in the human brain regions (thalamus, putamen, caudate, frontal cortex, pons, hypothalamus, hippocampus) examined by Northern blot analysis [1].

Expression Datasets
Show »« Hide 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] There should be a chart of expression data here, you may need to enable JavaScript!

Physiological Functions
Migration of macrophages into inflammatory tissue in obesity Species:  Mouse Tissue:  Adipose tissue and liver References:  3
Regulation of body weight and glucose metabolism Species:  Mouse Tissue:  References:  2

Physiological Consequences of Altering Gene Expression
Resistant to diet-induced obesity. Mice deficient for the GPR21 gene exhibit an increase in glucose tolerance and insulin sensitivity and a modest lean phenotype. Species:  Mouse Tissue:  Embryonic stem cells Technique:  Knockout (deletion of exon) References:  2-3
Mice with deletion of GPR21 are protected from obesity-induced inflammation and insulin resistance, with reduced macrophage infiltration into adipose tissue and liver. GPR21 KO macrophages do not undergo cytoskeletal reorganisation and display defective chemotactic activity in response to adipocyte conditioned medium. Species:  Mouse Tissue:  Macrophage Technique:  Knockout References:  3

Biologically Significant Variants
Type:  Single nucleotide polymorphism Species:  Human Amino acid change:  F212V Global MAF (%):  2 Subpopulation MAF (%):  AFR|AMR: 6|1 Minor allele count:  G=0.017/38 Comment on frequency:  Low frequency (<10% in all tested populations) SNP accession:  rs61736065 Validation:  1000 Genomes, Frequency

General Comments
GPR21 contains a lysine residue in an analogous position to that of the endothelin receptor which is important for its binding to a peptide agonist [2].