GPR42

Summary

GPR42 (G protein-coupled receptor 42, HGNC:4500) is a protein-coding gene on chromosome 19q13.12, encoding G-protein coupled receptor 42 (O15529). G protein-coupled receptor that is activated by short chain fatty acids (SCFAs), such as propionate.

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 2866 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001348195

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4500
Approved symbol	GPR42
Name	G protein-coupled receptor 42
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	GPR41L, FFAR3L
Ensembl gene	ENSG00000126251
Ensembl biotype	protein_coding
OMIM	603822
Entrez	2866

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000454971, ENST00000597214

RefSeq mRNA: 1 — MANE Select: NM_001348195 NM_001348195

CCDS: CCDS12460

Canonical transcript exons

ENST00000454971 — 2 exons

Exon	Start	End
ENSE00001657462	35371068	35371118
ENSE00001787973	35371349	35372962

Expression profiles

Bgee: expression breadth broad, 41 present calls, max score 57.79.

Top tissues by expression

115 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	57.79	gold quality
colonic epithelium	UBERON:0000397	52.01	gold quality
omental fat pad	UBERON:0010414	49.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	46.02	gold quality
bone marrow cell	CL:0002092	44.75	gold quality
adipose tissue	UBERON:0001013	44.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	43.88	silver quality
islet of Langerhans	UBERON:0000006	41.35	gold quality
granulocyte	CL:0000094	41.07	gold quality
colon	UBERON:0001155	40.19	gold quality
bone marrow	UBERON:0002371	40.08	gold quality
vermiform appendix	UBERON:0001154	40.00	gold quality
subcutaneous adipose tissue	UBERON:0002190	39.64	gold quality
skeletal muscle tissue	UBERON:0001134	39.34	gold quality
intestine	UBERON:0000160	38.97	gold quality
lower esophagus mucosa	UBERON:0035834	38.49	gold quality
urinary bladder	UBERON:0001255	37.93	silver quality
thoracic mammary gland	UBERON:0005200	37.54	gold quality
ganglionic eminence	UBERON:0004023	37.26	gold quality
gall bladder	UBERON:0002110	37.24	silver quality
muscle tissue	UBERON:0002385	37.17	silver quality
small intestine	UBERON:0002108	36.81	gold quality
placenta	UBERON:0001987	36.59	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
mucosa of transverse colon	UBERON:0004991	36.31	gold quality
sural nerve	UBERON:0015488	36.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	35.62	gold quality
transverse colon	UBERON:0001157	35.53	silver quality
liver	UBERON:0002107	35.05	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.22

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Study presents evidence showing that the six amino acid differences, including that R/W174 are polymorphisms rather than gene-specific differences between GPR41 and GPR42. (PMID:19630535)
• Our data suggest that GPR42 be reclassified as a functioning gene and that recognition of sequence and copy number polymorphism of the FFAR3/GPR42 complex be considered during genetic and pharmacological investigation of these receptors. (PMID:26260360)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-211g8.7	ENSDARG00000058535
danio_rerio	si:dkey-211g8.6	ENSDARG00000063088
danio_rerio		ENSDARG00000079661
danio_rerio	si:ch73-90p23.1	ENSDARG00000097901
mus_musculus	Ffar3	ENSMUSG00000019429
rattus_norvegicus	Ffar3	ENSRNOG00000037467

Paralogs (15): GPR31 (ENSG00000120436), FFAR2 (ENSG00000126262), FFAR1 (ENSG00000126266), OXER1 (ENSG00000162881), OXGR1 (ENSG00000165621), P2RY1 (ENSG00000169860), P2RY6 (ENSG00000171631), GPR82 (ENSG00000171657), P2RY2 (ENSG00000175591), HCAR2 (ENSG00000182782), FFAR3 (ENSG00000185897), P2RY4 (ENSG00000186912), HCAR1 (ENSG00000196917), SUCNR1 (ENSG00000198829), HCAR3 (ENSG00000255398)

Protein

Protein identifiers

G-protein coupled receptor 42 — O15529 (reviewed: O15529)

All UniProt accessions (2): O15529, A0A0K0PUY3

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor that is activated by short chain fatty acids (SCFAs), such as propionate. Hence may play a role in the regulation of whole-body energy homeostasis and/or in intestinal immunity.

Subcellular location. Cell membrane.

Polymorphism. The sequence shown in this entry differs from the translation of the reference genome assembly (GRCh38/hg38) due to a missense variant at position 174, p.Arg174Trp, in the reference genome, that results in the loss of response to short chain fatty acids, including propionate. The sequence shown in this entry is that of variant p.Trp174Arg. This variant is activated by propionate and has a frequency of about 15% in the human population according to the Genome Aggregation Database (gnomAD v2.1.1).

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_001335124* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR013312	GPR40-rel_orph	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (25 total): topological domain 8, transmembrane region 7, sequence variant 6, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15529-F1	87.53	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 166

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 15 (showing top): ATF3_Q6, OCT1_B, TGGAAA_NFAT_Q4_01, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, ZNF146_TARGET_GENES, WP_GPCRS_CLASS_A_RHODOPSINLIKE, DESCARTES_MAIN_FETAL_NEUROENDOCRINE_CELLS, ZNF260_TARGET_GENES, OSMAN_BLOOD_CHAD63_KH_AGE_18_50YO_HIGH_DOSE_SUBJECTS_24HR_UP, GOMF_MOLECULAR_TRANSDUCER_ACTIVITY, chr19q13, OCT1_01, TGAYRTCA_ATF3_Q6

GO Biological Process (2): G protein-coupled receptor signaling pathway (GO:0007186), signal transduction (GO:0007165)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	1
signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR42	CD22	P20273	769
GPR42	GAL	P22466	765
GPR42	PYY	P10082	498
GPR42	SLC52A2	Q9HAB3	434
GPR42	GALR2	O43603	356
GPR42	OR51E1	Q8TCB6	353
GPR42	OR2A14	Q96R47	348
GPR42	GALR1	P47211	324
GPR42	GCG	P01275	322
GPR42	MRGPRX1	Q96LB2	308
GPR42	OR51E2	Q9H255	306
GPR42	TAS2R16	Q9NYV7	290
GPR42	MRGPRX3	Q96LB0	286
GPR42	TAS2R7	Q9NYW3	279
GPR42	GPR150	Q8NGU9	275

IntAct

313 interactions, top by confidence:

A	B	Type	Score
CXCL9	GPR42	psi-mi:“MI:0915”(physical association)	0.560
MS4A1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
SLC41A2	GPR42	psi-mi:“MI:0915”(physical association)	0.560
YIF1A	GPR42	psi-mi:“MI:0915”(physical association)	0.560
SERINC1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
IL1RL1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
STX8	GPR42	psi-mi:“MI:0915”(physical association)	0.560
SLC39A2	GPR42	psi-mi:“MI:0915”(physical association)	0.560
SLC30A2	GPR42	psi-mi:“MI:0915”(physical association)	0.560
ANKRD46	GPR42	psi-mi:“MI:0915”(physical association)	0.560
PAEP	GPR42	psi-mi:“MI:0915”(physical association)	0.560
CCDC167	GPR42	psi-mi:“MI:0915”(physical association)	0.560
IER3IP1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
ERMP1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
TMEM239	GPR42	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	GPR42	psi-mi:“MI:0915”(physical association)	0.560
LTC4S	GPR42	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
EMP1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
TMBIM6	GPR42	psi-mi:“MI:0915”(physical association)	0.560
TEX264	GPR42	psi-mi:“MI:0915”(physical association)	0.560
GJB2	GPR42	psi-mi:“MI:0915”(physical association)	0.560

ESM2 similar proteins: A0A6I8PUB9, O00155, O00270, O14842, O14843, O15529, O43603, O46685, O60755, O88626, O88634, O88853, O88854, O88855, P0C5I1, P46092, P46093, P50132, Q149R9, Q15722, Q15743, Q1JQB3, Q3T181, Q3UFD7, Q3ZC80, Q4KLH9, Q6XKD3, Q76JU8, Q76JU9, Q76JV1, Q86VZ1, Q8BUD0, Q8BYC4, Q8HYC3, Q8K3T4, Q8TDS5, Q8TDU9, Q920E0, Q924U0, Q96G91

Diamond homologs: A0A4W3GG95, A0A6I8PUB9, B2GV46, B5X337, D4A7K7, E7FEL0, E9QJ73, F8VQN3, O00270, O08726, O08858, O14842, O14843, O15529, O42179, O43603, O46685, O60755, O77408, O88410, O88626, O88634, O88853, P21109, P23944, P25024, P25025, P35344, P35383, P35414, P41231, P41232, P46092, P46093, P49652, P49682, P49683, P50132, P51675, P51679

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 102 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SLC-mediated transmembrane transport	6	6.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

72 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35371347:A:AG	acceptor_gain	1.0000
19:35371347:AGT:A	acceptor_gain	1.0000
19:35371347:AGTG:A	acceptor_gain	1.0000
19:35371348:G:GT	acceptor_gain	1.0000
19:35371348:GT:G	acceptor_gain	1.0000
19:35371348:GTG:G	acceptor_gain	1.0000
19:35371348:GTGG:G	acceptor_gain	1.0000
19:35371345:C:G	acceptor_gain	0.9900
19:35371345:CCA:C	acceptor_loss	0.9900
19:35371346:CAG:C	acceptor_loss	0.9900
19:35371347:A:T	acceptor_loss	0.9900
19:35371348:GTGGC:G	acceptor_gain	0.9900
19:35371344:A:AG	acceptor_gain	0.9700
19:35371116:CAG:C	donor_loss	0.9500
19:35371117:AGGT:A	donor_loss	0.9500
19:35371119:G:GA	donor_loss	0.9500
19:35371120:T:A	donor_loss	0.9500
19:35371349:T:TA	acceptor_gain	0.9400
19:35371115:GCAG:G	donor_gain	0.9300
19:35371347:AGTGG:A	acceptor_gain	0.9300
19:35371346:CAGTG:C	acceptor_gain	0.9100
19:35371436:T:TA	acceptor_gain	0.9100
19:35371350:G:A	acceptor_gain	0.8900
19:35371345:CCAG:C	acceptor_gain	0.8500
19:35371344:ACCAG:A	acceptor_gain	0.8400
19:35371348:G:T	acceptor_gain	0.8400
19:35371343:CACCA:C	acceptor_gain	0.8200
19:35371105:TCTCA:T	donor_gain	0.8000
19:35371119:G:GG	donor_gain	0.7100
19:35371843:AGC:A	acceptor_gain	0.6300

AlphaMissense

2233 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35371687:A:C	S110R	0.982
19:35371689:C:A	S110R	0.982
19:35371689:C:G	S110R	0.982
19:35371765:A:C	S136R	0.981
19:35371767:T:A	S136R	0.981
19:35371767:T:G	S136R	0.981
19:35371801:A:C	S148R	0.980
19:35371803:C:A	S148R	0.980
19:35371803:C:G	S148R	0.980
19:35371602:G:C	W81C	0.967
19:35371602:G:T	W81C	0.967
19:35371441:G:A	G28R	0.965
19:35371441:G:C	G28R	0.965
19:35371936:T:C	F193L	0.964
19:35371938:T:A	F193L	0.964
19:35371938:T:G	F193L	0.964
19:35372152:A:C	S265R	0.963
19:35372154:C:A	S265R	0.963
19:35372154:C:G	S265R	0.963
19:35372163:C:A	N268K	0.962
19:35372163:C:G	N268K	0.962
19:35371527:C:A	N56K	0.958
19:35371527:C:G	N56K	0.958
19:35372071:T:C	F238L	0.957
19:35372073:T:A	F238L	0.957
19:35372073:T:G	F238L	0.957
19:35372128:T:A	W257R	0.956
19:35372128:T:C	W257R	0.956
19:35371442:G:A	G28E	0.954
19:35372059:T:C	F234L	0.954

dbSNP variants (sampled 300 via entrez): RS1001619171 (19:35373329 C>T), RS1002470338 (19:35371056 C>T), RS1002753406 (19:35371252 G>A), RS1006914625 (19:35373298 T>A), RS1008992711 (19:35370402 G>C,T), RS1010978519 (19:35369465 C>A,G,T), RS1011315555 (19:35371088 C>T), RS1012499929 (19:35369372 A>G), RS1012868319 (19:35370817 A>G), RS1013228969 (19:35371026 T>C), RS1016248476 (19:35373301 G>A), RS1016691941 (19:35372966 T>C), RS1017756109 (19:35372807 G>A), RS1018194741 (19:35372277 C>T), RS1022635392 (19:35370461 A>G)

Disease associations

OMIM: gene MIM:603822 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Free fatty acid receptors

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.