Gene and Protein Information
class A G protein-coupled receptor: probable pseudogene
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	7	346	19q13.12	GPR42	G protein-coupled receptor 42	3-4

Previous and Unofficial Names

FFAR1L | GPR41L | FFAR3L | G protein-coupled receptor 42 (gene/pseudogene)

Database Links
Specialist databases
GPCRdb	gpr42_human (Hs), gpr42_human (Hs)
Other databases
Alphafold	O15529 (Hs)
Ensembl Gene	ENSG00000126251 (Hs)
Entrez Gene	2866 (Hs)
Human Protein Atlas	ENSG00000126251 (Hs)
KEGG Gene	hsa:2866 (Hs)
OMIM	603822 (Hs)
Pharos	O15529 (Hs)
RefSeq Nucleotide	NM_005304 (Hs)
RefSeq Protein	NP_005295 (Hs)
UniProtKB	O15529 (Hs)
Wikipedia	GPR42 (Hs)

Natural/Endogenous Ligands
Comments: Very closely related to FFA3. Might be a pseudogene.

Agonist Comments

GPR42 is thought to have arisen as a tandem duplication of FFA3 in the human lineage and has acquired mutations since duplication that abolish its ability to respond to carboxylate ions [1].

Primary Transduction Mechanisms
Comments:  GPR42 appears to have lost the ability to activate Gi family proteins in response to carboxylate ligands due to an amino acid change at position 174 [1].
References:

Tissue Distribution Comments

RT-PCR detected no signal for GPR42 mRNA in samples of normal human tissues [1] .

Functional Assays
W174R amino acid change is sufficient to restore the response of GPR42 to FFA3 agonist propionate, though at a significantly lower magnitude Species:  Rat Tissue:  HEK293T cells Response measured:  Receptor response to propionate References:  1

General Comments

Two conflicting hypotheses exist regarding GPR42: the first is that it is a pseudogene, occurring infrequently in human populations as a polymorphic insert [1]. Alternative evidence from genotyping data indicates that GPR42 may be a functional gene in a significant fraction of the population, where Arg174 is present [3]. However, the very close sequence similarity of FFA3 (formerly GPR41) and GPR42 (six nucleotide differences in the coding sequence) make this very difficult to assess. The receptor shares 98% sequence homology with free fatty acid receptor FFA3 [4]. Rodents appear to have only one ortholog of the human FFA3/GPR42 pair, suggesting duplication of the locus has occurred since divergence of primate and human lineages [2].