GPRC5C

Summary

GPRC5C (G protein-coupled receptor class C group 5 member C, HGNC:13309) is a protein-coding gene on chromosome 17q25.1, encoding G-protein coupled receptor family C group 5 member C (Q9NQ84). This retinoic acid-inducible G-protein coupled receptor provide evidence for a possible interaction between retinoid and G-protein signaling pathways.

The protein encoded by this gene is a member of the type 3 G protein-coupled receptor family. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The specific function of this protein is unknown; however, this protein may mediate the cellular effects of retinoic acid on the G protein signal transduction cascade. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 55890 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 106 total
• Druggable target: yes
• MANE Select transcript: NM_022036

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13309
Approved symbol	GPRC5C
Name	G protein-coupled receptor class C group 5 member C
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	RAIG-3
Ensembl gene	ENSG00000170412
Ensembl biotype	protein_coding
OMIM	605949
Entrez	55890

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000342648, ENST00000392627, ENST00000392628, ENST00000392629, ENST00000481232, ENST00000482723, ENST00000577663, ENST00000581590, ENST00000582444, ENST00000582473, ENST00000582873, ENST00000652232, ENST00000652294, ENST00000877273, ENST00000877274, ENST00000877275, ENST00000877276, ENST00000877277, ENST00000877278, ENST00000877279, ENST00000960002, ENST00000960003

RefSeq mRNA: 4 — MANE Select: NM_022036 NM_001366261, NM_001366262, NM_018653, NM_022036

CCDS: CCDS11699, CCDS92388

Canonical transcript exons

ENST00000392627 — 4 exons

Exon	Start	End
ENSE00001512530	74432088	74432141
ENSE00003505251	74443818	74443912
ENSE00003694555	74446849	74447429
ENSE00003842879	74439745	74440827

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 97.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.8385 / max 199.4155, expressed in 1026 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162604	5.8952	902
162602	1.1563	505
162606	0.8751	444
162609	0.5220	164
162603	0.5205	310
162607	0.2990	144
162605	0.2909	176
162608	0.1336	58
162610	0.0774	17
162601	0.0685	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.88	gold quality
metanephros cortex	UBERON:0010533	96.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.85	gold quality
mucosa of transverse colon	UBERON:0004991	96.77	gold quality
right lobe of thyroid gland	UBERON:0001119	96.29	gold quality
cerebellar hemisphere	UBERON:0002245	96.13	gold quality
left lobe of thyroid gland	UBERON:0001120	96.11	gold quality
cerebellar cortex	UBERON:0002129	96.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.80	gold quality
thyroid gland	UBERON:0002046	95.54	gold quality
body of pancreas	UBERON:0001150	95.35	gold quality
cerebellum	UBERON:0002037	95.24	gold quality
body of stomach	UBERON:0001161	95.21	gold quality
popliteal artery	UBERON:0002250	95.01	gold quality
tibial artery	UBERON:0007610	95.00	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.55	gold quality
gastrocnemius	UBERON:0001388	94.47	gold quality
descending thoracic aorta	UBERON:0002345	94.42	gold quality
aorta	UBERON:0000947	94.33	gold quality
right coronary artery	UBERON:0001625	94.33	gold quality
stomach	UBERON:0000945	94.23	gold quality
adult mammalian kidney	UBERON:0000082	94.21	gold quality
apex of heart	UBERON:0002098	93.81	gold quality
thoracic aorta	UBERON:0001515	93.67	gold quality
ascending aorta	UBERON:0001496	93.66	gold quality
liver	UBERON:0002107	93.61	gold quality
muscle of leg	UBERON:0001383	93.14	gold quality
left coronary artery	UBERON:0001626	92.98	gold quality
coronary artery	UBERON:0001621	92.43	gold quality
skin of leg	UBERON:0001511	92.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	18.57
E-ANND-3	yes	15.10
E-CURD-114	no	19.51
E-CURD-112	no	2.73

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Data suggest that agents (such as all-trans retinoic acid) that activate GPRC5C restore and/or maintain functional insulin-secreting cells; GPRC5C appears to play role in regulation of expression of genes controlling apoptosis, cell survival, and cell proliferation in insulin-secreting cells. (PMID:28228611)
• GPRC5C drives branched-chain amino acid metabolism in leukemogenesis. (PMID:37639313)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gprc5c	ENSDARG00000100862
mus_musculus	Gprc5c	ENSMUSG00000051043
rattus_norvegicus	Gprc5c	ENSRNOG00000003144

Paralogs (3): GPRC5A (ENSG00000013588), GPRC5D (ENSG00000111291), GPRC5B (ENSG00000167191)

Protein

Protein identifiers

G-protein coupled receptor family C group 5 member C — Q9NQ84 (reviewed: Q9NQ84)

Alternative names: Retinoic acid-induced gene 3 protein

All UniProt accessions (8): Q9NQ84, A0A0C4DFY5, A8MXZ4, J3KSD6, J3KTP8, J3QQN3, J9JIE0, Q9BSP0

UniProt curated annotations — full annotation on UniProt →

Function. This retinoic acid-inducible G-protein coupled receptor provide evidence for a possible interaction between retinoid and G-protein signaling pathways.

Subcellular location. Cell membrane. Cytoplasmic vesicle membrane.

Tissue specificity. Expression is highest in the periphery, particularly in the stomach, but also in the kidney, liver, pancreas, and prostate. In brain, levels of expression are generally lower than in the periphery, with the exception of cerebellum, spinal cord, and dorsal root ganglia (DRG).

Induction. By all-trans retinoic acid (ATRA).

Similarity. Belongs to the G-protein coupled receptor 3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NQ84-1	1	yes
Q9NQ84-2	2

RefSeq proteins (4): NP_001353190, NP_001353191, NP_061123, NP_071319* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017978	GPCR_3_C	Domain
IPR051753	RA-inducible_GPCR3	Family

Pfam: PF00003

UniProt features (27 total): topological domain 8, transmembrane region 7, modified residue 6, signal peptide 1, chain 1, region of interest 1, glycosylation site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQ84-F1	71.02	0.36

Functional residue map

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

Post-translational modifications (6): 344, 383, 403, 406, 414, 423

Glycosylation sites (1): 191

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 155 (showing top): RNGTGGGC_UNKNOWN, FREAC2_01, FOXO1_01, CHX10_01, USF_C, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOMF_KINASE_ACTIVATOR_ACTIVITY, MYCMAX_01, GROSS_HYPOXIA_VIA_HIF1A_DN, GOCC_CENTROSOME, HFH3_01, CREB_Q2_01, TGGNNNNNNKCCAR_UNKNOWN, MODULE_48, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON

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

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), protein kinase activator activity (GO:0030295), protein binding (GO:0005515)

GO Cellular Component (10): plasma membrane (GO:0005886), cilium (GO:0005929), cytoplasmic vesicle membrane (GO:0030659), vesicle (GO:0031982), centriolar satellite (GO:0034451), ciliary transition zone (GO:0035869), signaling receptor complex (GO:0043235), extracellular exosome (GO:0070062), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane-bounded organelle	2
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
protein kinase activity	1
kinase activator activity	1
protein kinase regulator activity	1
binding	1
membrane	1
cell periphery	1
intraciliary transport particle	1
plasma membrane bounded cell projection	1
vesicle membrane	1
cytoplasmic vesicle	1
centrosome	1
cilium	1
protein-containing complex	1
extracellular vesicle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

676 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPRC5C	GRM2	Q14416	833
GPRC5C	GPR158	Q5T848	530
GPRC5C	GPR156	Q8NFN8	492
GPRC5C	GPR137	Q96N19	450
GPRC5C	GPR149	Q86SP6	447
GPRC5C	TMEM150C	B9EJG8	447
GPRC5C	GPR107	Q5VW38	445
GPRC5C	GPR155	Q7Z3F1	444
GPRC5C	GPR63	Q9BZJ6	429
GPRC5C	ADGRG6	Q86SQ4	428
GPRC5C	PHACTR2	O75167	424
GPRC5C	GPR176	Q14439	422
GPRC5C	TTYH2	Q9BSA4	421
GPRC5C	GPR39	O43194	416
GPRC5C	MAN1A1	P33908	415

IntAct

100 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3B1	psi-mi:“MI:0914”(association)	0.530
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.530
TMEM171	THAP12	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
SCAMP2	SCAMP3	psi-mi:“MI:0914”(association)	0.530
KIAA2013	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
TMEM171	B3GAT3	psi-mi:“MI:0914”(association)	0.530
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	GPRC5C	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPRC5C	psi-mi:“MI:0915”(physical association)	0.400
GPRC5C	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	GPRC5C	psi-mi:“MI:0915”(physical association)	0.400
GPRC5C	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
M2	IPO5	psi-mi:“MI:0914”(association)	0.350

BioGRID (160): GPRC5C (Affinity Capture-MS), GPRC5C (Affinity Capture-MS), GPRC5C (Affinity Capture-MS), GPRC5C (Two-hybrid), GPRC5C (Affinity Capture-MS), GOLPH3L (Affinity Capture-MS), NMT2 (Affinity Capture-MS), PCYT1A (Affinity Capture-MS), BAIAP2L1 (Affinity Capture-MS), NMT1 (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), NNT (Affinity Capture-MS), C17orf75 (Affinity Capture-MS), GPRC5C (Affinity Capture-MS), CTAGE5 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVV1, A0M8S0, A0M8T1, A0M8U1, A3KN28, A4D7R9, A9JRA0, B1AZA5, E9Q2Z6, P01134, P48030, Q00PJ0, Q07DV5, Q07DW9, Q07DX8, Q07DY8, Q07E08, Q07E45, Q09YH4, Q09YI5, Q09YJ7, Q09YK8, Q09YN2, Q108U3, Q1RLU8, Q2IBA8, Q2IBD0, Q2IBE0, Q2IBE8, Q2PG42, Q2QL86, Q2QLA6, Q2QLB7, Q2QLD7, Q2QLE8, Q2QLG2, Q3KRC4, Q3SXP7, Q5T292, Q68FW3

Diamond homologs: Q2YDG0, Q3KRC4, Q8BHL4, Q8K3J9, Q8NFJ5, Q923Z0, Q9JIL6, Q9NQ84, Q9NZD1, Q9NZH0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
Class A/1 (Rhodopsin-like receptors)	9	7.8×	4e-04
G alpha (s) signalling events	9	7.7×	4e-04
G alpha (q) signalling events	9	6.0×	2e-03
GPCR ligand binding	8	6.0×	3e-03
Signaling by GPCR	10	4.7×	3e-03
GPCR downstream signalling	9	4.5×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	7	13.4×	2e-04
adenylate cyclase-activating G protein-coupled receptor signaling pathway	11	10.9×	4e-06
positive regulation of cytosolic calcium ion concentration	10	10.3×	2e-05
phospholipase C-activating G protein-coupled receptor signaling pathway	8	9.2×	4e-04
establishment of localization in cell	6	8.4×	7e-03
protein localization to plasma membrane	7	6.7×	7e-03
G protein-coupled receptor signaling pathway	14	4.5×	4e-04
protein transport	11	4.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

932 predictions. Top by Δscore:

Variant	Effect	Δscore
17:74439740:TCTA:T	acceptor_loss	1.0000
17:74439743:A:AC	acceptor_loss	1.0000
17:74439743:A:AG	acceptor_gain	1.0000
17:74439743:AG:A	acceptor_gain	1.0000
17:74439743:AGG:A	acceptor_gain	1.0000
17:74439744:G:A	acceptor_gain	1.0000
17:74439744:G:GT	acceptor_gain	1.0000
17:74439744:GGG:G	acceptor_gain	1.0000
17:74439744:GGGA:G	acceptor_gain	1.0000
17:74439744:GGGAC:G	acceptor_gain	1.0000
17:74440822:TTGC:T	donor_gain	1.0000
17:74440823:TGCAG:T	donor_loss	1.0000
17:74440825:CAG:C	donor_loss	1.0000
17:74440826:AG:A	donor_loss	1.0000
17:74440827:GG:G	donor_loss	1.0000
17:74440829:T:G	donor_loss	1.0000
17:74443815:TAGCT:T	acceptor_loss	1.0000
17:74443816:A:AG	acceptor_gain	1.0000
17:74443816:A:AT	acceptor_loss	1.0000
17:74443817:G:A	acceptor_loss	1.0000
17:74443817:G:GG	acceptor_gain	1.0000
17:74443817:GC:G	acceptor_gain	1.0000
17:74443817:GCT:G	acceptor_gain	1.0000
17:74443817:GCTA:G	acceptor_gain	1.0000
17:74443817:GCTAA:G	acceptor_gain	1.0000
17:74443910:CCGG:C	donor_loss	1.0000
17:74443912:GGT:G	donor_loss	1.0000
17:74443913:G:GG	donor_gain	1.0000
17:74443914:T:G	donor_loss	1.0000
17:74446847:A:AG	acceptor_gain	1.0000

AlphaMissense

2869 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:74440803:T:C	F343L	0.998
17:74440805:T:A	F343L	0.998
17:74440805:T:G	F343L	0.998
17:74440804:T:G	F343C	0.995
17:74440804:T:C	F343S	0.994
17:74440795:A:T	N340I	0.993
17:74440796:C:A	N340K	0.993
17:74440796:C:G	N340K	0.993
17:74439954:G:C	G60R	0.987
17:74439955:G:A	G60D	0.987
17:74440551:T:A	W259R	0.987
17:74440551:T:C	W259R	0.987
17:74440785:T:C	F337L	0.987
17:74440787:C:A	F337L	0.987
17:74440787:C:G	F337L	0.987
17:74439923:G:C	W49C	0.985
17:74439923:G:T	W49C	0.985
17:74440799:G:C	K341N	0.985
17:74440799:G:T	K341N	0.985
17:74440062:G:A	G96R	0.984
17:74440062:G:C	G96R	0.984
17:74440792:A:T	E339V	0.983
17:74440542:T:A	W256R	0.982
17:74440542:T:C	W256R	0.982
17:74440143:T:C	F123L	0.981
17:74440145:T:A	F123L	0.981
17:74440145:T:G	F123L	0.981
17:74440298:G:C	W174C	0.981
17:74440298:G:T	W174C	0.981
17:74440296:T:A	W174R	0.980

dbSNP variants (sampled 300 via entrez): RS1000013361 (17:74442072 G>A), RS1000063068 (17:74449170 G>A), RS1000071447 (17:74436417 G>T), RS1000081342 (17:74443315 G>A), RS1000093808 (17:74448995 C>A,G,T), RS1000397188 (17:74443598 T>G), RS1000531554 (17:74442337 G>A), RS1000652773 (17:74433508 C>T), RS1000664286 (17:74451398 G>A,T), RS1000902856 (17:74431179 CG>C), RS1001089523 (17:74433173 A>G), RS1001181359 (17:74451523 C>A), RS1001258694 (17:74448602 C>T), RS1001526996 (17:74431415 A>AG), RS1001553333 (17:74431508 G>C,T)

Disease associations

OMIM: gene MIM:605949 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009365_1	LDL cholesterol levels x short total sleep time interaction (2df test)	1.000000e-08
GCST90013406_271	Liver enzyme levels (alkaline phosphatase)	1.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523921 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Class C Orphans

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	5
Tetrachlorodibenzodioxin	increases expression	4
Valproic Acid	affects expression, decreases expression	4
methylmercuric chloride	increases expression, decreases expression	2
Acetaminophen	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	decreases expression	1
Leflunomide	increases expression	1
Amiodarone	increases expression	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Cytarabine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	decreases expression	1
Estradiol	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883478	Binding	PRESTO-Tango GPCRome screening (GPRC5C)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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