GPRC6A

Summary

GPRC6A (G protein-coupled receptor class C group 6 member A, HGNC:18510) is a protein-coding gene on chromosome 6q22.1, encoding G-protein coupled receptor family C group 6 member A (Q5T6X5). Receptor activated by multiple ligands, including osteocalcin (BGLAP), basic amino acids, and various cations.

Members of family C of the G protein-coupled receptor (GPCR) superfamily, such as GPRC6A, are characterized by an evolutionarily conserved amino acid-sensing motif linked to an intramembranous 7-transmembrane loop region. Several members of GPCR family C, including GPRC6A, also have a long N-terminal domain (summary by Pi et al., 2005 [PubMed 16199532]).

Source: NCBI Gene 222545 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 140 total
• Druggable target: yes
• MANE Select transcript: NM_148963

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18510
Approved symbol	GPRC6A
Name	G protein-coupled receptor class C group 6 member A
Location	6q22.1
Locus type	gene with protein product
Status	Approved
Aliases	bA86F4.3
Ensembl gene	ENSG00000173612
Ensembl biotype	protein_coding
OMIM	613572
Entrez	222545

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000310357, ENST00000368549, ENST00000530250

RefSeq mRNA: 3 — MANE Select: NM_148963 NM_001286354, NM_001286355, NM_148963

CCDS: CCDS5112, CCDS69184, CCDS69185

Canonical transcript exons

ENST00000310357 — 6 exons

Exon	Start	End
ENSE00001209962	116795712	116795835
ENSE00001209967	116800584	116800796
ENSE00001209972	116806370	116807206
ENSE00001209976	116809314	116809617
ENSE00001209984	116792085	116793250
ENSE00002165316	116828820	116829083

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 79.26.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.26	gold quality
adrenal tissue	UBERON:0018303	69.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	53.55	gold quality
saliva-secreting gland	UBERON:0001044	48.82	gold quality
minor salivary gland	UBERON:0001830	47.65	gold quality
islet of Langerhans	UBERON:0000006	46.78	gold quality
adult mammalian kidney	UBERON:0000082	45.27	gold quality
right adrenal gland	UBERON:0001233	43.42	gold quality
adrenal gland	UBERON:0002369	42.33	gold quality
right adrenal gland cortex	UBERON:0035827	42.24	gold quality
kidney	UBERON:0002113	41.86	gold quality
colonic epithelium	UBERON:0000397	41.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	39.50	gold quality
left adrenal gland	UBERON:0001234	39.18	gold quality
bone marrow cell	CL:0002092	38.27	gold quality
cortex of kidney	UBERON:0001225	38.12	gold quality
left adrenal gland cortex	UBERON:0035825	37.13	gold quality
tonsil	UBERON:0002372	36.52	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
placenta	UBERON:0001987	36.30	gold quality
skeletal muscle tissue	UBERON:0001134	36.27	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
mucosa of transverse colon	UBERON:0004991	34.42	gold quality
muscle tissue	UBERON:0002385	34.39	gold quality
monocyte	CL:0000576	34.11	gold quality
leukocyte	CL:0000738	33.53	gold quality
bone marrow	UBERON:0002371	32.82	gold quality
rectum	UBERON:0001052	31.97	silver quality
pancreas	UBERON:0001264	31.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.43

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 26)

• GPRC6A is widely expressed in brain and peripheral tissues with highest levels in kidney, skeletal muscle, testis, and leucocytes. (PMID:15194188)
• elucidating agonist interaction with GPRC6A, a novel family C G-protein-coupled receptor. (PMID:15576628)
• GPRC6A is a cation-, calcimimetic-, and osteocalcin-sensing receptor (PMID:16199532)
• that GPRC6A gene polymorphisms were significantly associated with human spine BMD. (PMID:19874200)
• GPRC6A is a novel molecular target for regulating prostate growth and cancer progression. (PMID:21681779)
• Our results provide further support for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in Eastern Asian populations (PMID:22662242)
• the GPRC6A receptor functions as an amino acid sensor in GLUTag cells that promotes GLP-1 secretion (PMID:23269670)
• Extracellular Ca2+ activates the NLRP3 inflammasome via CaSR and GPRC6A. (PMID:23271661)
• The F464Y substitution in GPRC6A may be a cause of primary testicular failure. (PMID:23728177)
• The present experiments demonstrated a critical role for the GPRC6A-ERK1/2 and PI3K/Akt signaling pathway in arginine-mediated fibroblast survival. (PMID:24651445)
• Duox1 activity is stimulated by testosterone through GPRC6A in skin keratinocytes (PMID:25164816)
• association of the THADA, FOXP4, GPRC6A/RFX6 and 8q24 genes with prostate cancer in Asian populations. (PMID:26537068)
• results suggest that G protein-coupled receptor class C group 6 member A(GPRC6A) inactivation or sub-function contributes to reduced exposure to androgens, leading to cryptorchidism during fetal life and/or low sperm production in adulthood (PMID:26735260)
• Osteocalcin and Sex Hormone Binding Globulin Compete on a Specific Binding Site of GPRC6A. (PMID:27673554)
• he nonrare polymorphism rs2274911 in the GPRC6A gene was associated with insulin resistance features, independently of the metabolic phenotype and osteocalcin levels. (PMID:27696500)
• Genetic Variations in the Human G Protein-coupled Receptor Class C, Group 6, Member A (GPRC6A) Control Cell Surface Expression and Function (PMID:27986810)
• If the regulatory functions of GPRC6A identified in mice translate to humans, and polymorphisms in GPRC6A are found to predict racial disparities in human diseases, GPRC6A may be a new gene target to predict, prevent, and treat MetS, PCa, and other disorders impacted by GPRC6A. (PMID:28180060)
• Human GPRC6A is a functional osteocalcin and testosterone sensing receptor that promotes prostate cancer progression. (PMID:28659174)
• The G protein-coupled receptor family C group 6 member A (GPRC6A) and zinc transporter member 9 (ZIP9) have also been portrayed as mARs, related to the extranuclear action of androgens. (PMID:30707908)
• Human GPRC6A is required for mediating the effects of testosterone on cell proliferation and autophagy. (PMID:30894404)
• SHBG141-161 Domain-Peptide Stimulates GPRC6A-Mediated Response in Leydig and beta-Langerhans cell lines. (PMID:31857654)
• Humanized GPRC6A(KGKY) is a gain-of-function polymorphism in mice. (PMID:32636482)
• rs2274911 polymorphism in GPRC6A associated with serum E2 and PSA in a Southern Chinese male population. (PMID:32827681)
• Analysis of GPRC6A variants in different pancreatitis etiologies. (PMID:32859544)
• Explaining Divergent Observations Regarding Osteocalcin/GPRC6A Endocrine Signaling. (PMID:33474566)
• RS 2247911 polymorphism of GPRC6A gene and serum undercarboxylated-osteocalcin are associated with testis function. (PMID:35482214)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gprc6a	ENSDARG00000005371
mus_musculus	Gprc6a	ENSMUSG00000019905
rattus_norvegicus	Gprc6a	ENSRNOG00000000401

Paralogs (4): CASR (ENSG00000036828), TAS1R3 (ENSG00000169962), TAS1R1 (ENSG00000173662), TAS1R2 (ENSG00000179002)

Protein

Protein identifiers

G-protein coupled receptor family C group 6 member A — Q5T6X5 (reviewed: Q5T6X5)

Alternative names: G-protein coupled receptor GPCR33

All UniProt accessions (1): Q5T6X5

UniProt curated annotations — full annotation on UniProt →

Function. Receptor activated by multiple ligands, including osteocalcin (BGLAP), basic amino acids, and various cations. Activated by amino acids with a preference for basic amino acids such as L-Lys, L-Arg and L-ornithine but also by small and polar amino acids. The L-alpha amino acids respond is augmented by divalent cations Ca(2+) and Mg(2+). Seems to act through a G(q)/G(11) and G(i)-coupled pathway. Regulates testosterone production by acting as a ligand for uncarboxylated osteocalcin hormone: osteocalcin-binding at the surface of Leydig cells initiates a signaling response that promotes the expression of enzymes required for testosterone synthesis in a CREB-dependent manner. Mediates the non-genomic effects of androgens in multiple tissue. May coordinate nutritional and hormonal anabolic signals through the sensing of extracellular amino acids, osteocalcin, divalent ions and its responsiveness to anabolic steroids.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Cell membrane.

Tissue specificity. Isoform 1 is expressed at high level in brain, skeletal muscle, testis, bone, calvaria, osteoblasts and leukocytes. Expressed at intermediate level in liver, heart, kidney and spleen. Expressed at low level in lung, pancreas, placenta and ovary. Not detected in thymus, prostate, small intestine, tongue and colon. Isoform 1 and isoform 2 are expressed in kidney at the same level. Isoform 2 is expressed at lower level than isoform 1 in the other tissues.

Miscellaneous. Major isoform.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q5T6X5-1	1	yes
Q5T6X5-2	2
Q5T6X5-3	3

RefSeq proteins (3): NP_001273283, NP_001273284, NP_683766* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000068	GPCR_3_Ca_sens_rcpt-rel	Family
IPR000337	GPCR_3	Family
IPR001828	ANF_lig-bd_rcpt	Domain
IPR011500	GPCR_3_9-Cys_dom	Domain
IPR017978	GPCR_3_C	Domain
IPR017979	GPCR_3_CS	Conserved_site
IPR028082	Peripla_BP_I	Homologous_superfamily
IPR038550	GPCR_3_9-Cys_sf	Homologous_superfamily

Pfam: PF00003, PF01094, PF07562

UniProt features (34 total): glycosylation site 9, topological domain 8, transmembrane region 7, sequence variant 3, splice variant 2, mutagenesis site 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T6X5-F1	84.32	0.55

Functional residue map

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

Disulfide bonds (1): 131

Glycosylation sites (9): 121, 259, 332, 378, 452, 555, 567, 590, 733

Mutagenesis-validated functional residues (2):

Position	Phenotype
149	loss of function.
172	loss of function.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-420499	Class C/3 (Metabotropic glutamate/pheromone receptors)

MSigDB gene sets: 99 (showing top): GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, GOBP_HORMONE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_KETONE_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_INSULIN_SECRETION, GOBP_REGULATION_OF_PROTEIN_SECRETION

GO Biological Process (7): adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), calcium-mediated signaling (GO:0019722), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), response to amino acid (GO:0043200), regulation of testosterone biosynthetic process (GO:2000224), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), G protein-coupled peptide receptor activity (GO:0008528)

GO Cellular Component (3): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	2
cellular anatomical structure	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
intracellular signaling cassette	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
response to acid chemical	1
regulation of ketone biosynthetic process	1
regulation of steroid biosynthetic process	1
testosterone biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
peptide receptor activity	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1285 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPRC6A	BGLAP	P02818	974
GPRC6A	GPR158	Q5T848	772
GPRC6A	GNAQ	P50148	675
GPRC6A	SLC15A1	P46059	644
GPRC6A	SLC39A9	Q9NUM3	623
GPRC6A	OXER1	Q8TDS5	622
GPRC6A	ARRB1	P49407	614
GPRC6A	LPAR5	Q9H1C0	598
GPRC6A	CASR	P41180	591
GPRC6A	GNAI1	P04898	560
GPRC6A	TAS2R39	P59534	506
GPRC6A	TAS2R42	Q7RTR8	505
GPRC6A	TAS2R60	P59551	504
GPRC6A	GPR142	Q7Z601	491
GPRC6A	GCG	P01275	474

IntAct

127 interactions, top by confidence:

A	B	Type	Score
GPRC6A	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	GPRC6A	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
GRID2IP	GPRC6A	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	MPP7	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	AHNAK	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	GRIP1	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	LDB3	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	FRMPD1	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF11	GPRC6A	psi-mi:“MI:0407”(direct interaction)	0.440
WHRN	GPRC6A	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC6A	PDLIM1	psi-mi:“MI:0407”(direct interaction)	0.440

ESM2 similar proteins: A0A0G2K1Q8, A3QNZ8, A3QNZ9, A3QP00, A3QP01, A3QP07, A3QP08, A3QP09, D4A3T6, E1BPQ3, E9Q4J9, E9Q6I0, G5ECB2, O35659, O62714, O70410, O75899, O88871, P32082, P35384, P41180, P43220, P48442, P48960, Q49HI0, Q58Y75, Q5T6X5, Q5U9X3, Q61606, Q6TAC4, Q70VB1, Q717C1, Q7RTX1, Q80T41, Q8BG22, Q8K385, Q8K4Z6, Q8R420, Q8SQA4, Q8TE23

Diamond homologs: E1BPQ3, O62714, P35384, P41180, P48442, Q5T6X5, Q5U9X3, Q70VB1, Q8K4Z6, Q9PW88, Q9QY96, A3QNZ8, A3QNZ9, A3QP00, A3QP01, A3QP07, A3QP08, E9Q6I0, O00222, O15303, O70410, P31421, P31422, P31423, P35349, P35400, P41594, P47743, P70579, Q14416, Q14831, Q14832, Q14833, Q14BI2, Q1ZZH0, Q1ZZH1, Q5NCH9, Q5RAL3, Q5RDQ8, Q68ED2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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
Ras activation upon Ca2+ influx through NMDA receptor	5	52.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	50.4×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	50.4×	1e-06
Long-term potentiation	5	44.1×	2e-06
Assembly and cell surface presentation of NMDA receptors	9	42.3×	4e-11
Neurexins and neuroligins	10	36.5×	2e-11
Protein-protein interactions at synapses	6	29.5×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	72.6×	3e-14
protein localization to synapse	6	57.5×	1e-07
receptor clustering	7	54.6×	9e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	6	37.2×	1e-06
bicellular tight junction assembly	5	20.6×	2e-04
protein-containing complex assembly	9	12.8×	2e-06
cell-cell adhesion	10	12.7×	6e-07
protein localization to plasma membrane	8	10.9×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	123
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

754 predictions. Top by Δscore:

Variant	Effect	Δscore
6:116793248:TAT:T	acceptor_gain	1.0000
6:116795833:TTG:T	acceptor_gain	1.0000
6:116795836:C:CC	acceptor_gain	1.0000
6:116795841:T:TC	acceptor_gain	1.0000
6:116800579:GTTAC:G	donor_loss	1.0000
6:116800580:TTAC:T	donor_loss	1.0000
6:116800581:TACC:T	donor_loss	1.0000
6:116800582:ACCTT:A	donor_loss	1.0000
6:116800583:CCTTA:C	donor_loss	1.0000
6:116800602:A:AC	donor_gain	1.0000
6:116800603:T:C	donor_gain	1.0000
6:116800612:T:TA	donor_gain	1.0000
6:116800792:AGTAA:A	acceptor_gain	1.0000
6:116800793:GTAA:G	acceptor_gain	1.0000
6:116800794:TAA:T	acceptor_gain	1.0000
6:116800794:TAAC:T	acceptor_loss	1.0000
6:116800795:AAC:A	acceptor_loss	1.0000
6:116800796:ACTAT:A	acceptor_loss	1.0000
6:116800797:C:CA	acceptor_loss	1.0000
6:116800797:C:CC	acceptor_gain	1.0000
6:116800798:T:A	acceptor_loss	1.0000
6:116828814:A:AC	donor_gain	1.0000
6:116828815:C:CC	donor_gain	1.0000
6:116828815:CT:C	donor_gain	1.0000
6:116828815:CTCA:C	donor_gain	1.0000
6:116828816:TCA:T	donor_loss	1.0000
6:116828818:A:AC	donor_gain	1.0000
6:116828818:AC:A	donor_gain	1.0000
6:116828819:C:A	donor_loss	1.0000
6:116828819:C:CC	donor_gain	1.0000

AlphaMissense

6198 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:116806810:A:G	W299R	0.991
6:116806810:A:T	W299R	0.991
6:116807083:A:G	W208R	0.974
6:116807083:A:T	W208R	0.974
6:116807159:A:C	F182L	0.970
6:116807159:A:T	F182L	0.970
6:116807161:A:G	F182L	0.970
6:116806808:C:A	W299C	0.969
6:116806808:C:G	W299C	0.969
6:116806799:A:C	S302R	0.968
6:116806799:A:T	S302R	0.968
6:116806801:T:G	S302R	0.968
6:116806792:A:G	W305R	0.967
6:116806792:A:T	W305R	0.967
6:116806803:G:T	A301D	0.962
6:116795807:C:G	C526S	0.957
6:116795808:A:T	C526S	0.957
6:116809388:C:G	A142P	0.952
6:116828895:C:T	G40D	0.952
6:116793229:C:G	C565S	0.951
6:116793230:A:T	C565S	0.951
6:116795819:C:G	C522S	0.950
6:116795820:A:T	C522S	0.950
6:116809387:G:T	A142D	0.950
6:116806982:G:C	F241L	0.948
6:116806982:G:T	F241L	0.948
6:116806984:A:G	F241L	0.948
6:116793187:C:G	C579S	0.947
6:116793188:A:T	C579S	0.947
6:116806809:C:G	W299S	0.947

dbSNP variants (sampled 300 via entrez): RS1000007307 (6:116811885 C>A), RS1000038614 (6:116811721 C>A), RS1000044057 (6:116808172 A>G), RS1000071199 (6:116815961 C>T), RS1000094362 (6:116820706 T>C), RS1000123383 (6:116815713 A>G), RS1000277422 (6:116805035 G>T), RS1000289178 (6:116816539 A>T), RS1000701545 (6:116810652 T>C), RS1000710964 (6:116804743 T>A,C), RS1000751723 (6:116799343 A>G), RS1000776065 (6:116796219 T>C,G), RS1000864795 (6:116824843 A>G), RS1000894637 (6:116819440 T>C,G), RS1000943442 (6:116830766 T>C)

Disease associations

OMIM: gene MIM:613572 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): disorder of sexual differentiation (MONDO:0002145)

Orphanet (1): Difference of sex development (Orphanet:90771)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000750_4	Prostate cancer	2.000000e-12
GCST000965_20	C-reactive protein levels	5.000000e-08
GCST003602_8	Inflammatory bowel disease	5.000000e-06
GCST008363_113	Offspring birth weight	5.000000e-08
GCST009391_545	Metabolite levels	2.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0010496	hippuric acid measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D012734	Disorders of Sex Development	C12.050.351.875.253; C12.200.706.316; C12.800.316; C16.131.939.316; C19.391.119

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523873 (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

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
NPS 2143	Negative	5.0	pIC50
calindol	Negative	5.0	pIC50
L-arginine	Full agonist	4.4	pEC50
L-ornithine	Full agonist	4.0	pEC50
L-alanine	Full agonist	3.8	pEC50
L-lysine	Full agonist	3.8	pEC50
L-citrulline	Full agonist	3.6	pEC50
glycine	Full agonist	3.6	pEC50
L-glutamine	Full agonist	3.2	pEC50
L-serine	Full agonist	3.2	pEC50

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
Lipopolysaccharides	increases expression, affects cotreatment, affects response to substance	1
Dronabinol	increases methylation	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
CHEMBL4883480	Binding	PRESTO-Tango GPCRome screening (GPRC6A)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03718234	PHASE1	COMPLETED	Subcutaneous Hydrocortisone Children With Congenital Adrenal Hyperplasia
NCT00485186	Not specified	WITHDRAWN	Gene Polymorphisms Influencing Steroid Synthesis and Action
NCT01875640	Not specified	COMPLETED	Decision Support for Parents Receiving Information About Child’s Rare Disease
NCT02784184	Not specified	UNKNOWN	COPENHAGEN Minipuberty Study
NCT03102554	Not specified	ENROLLING_BY_INVITATION	Genetics of Differences of Sex Development and Hypospadias
NCT03283852	Not specified	RECRUITING	Identifying New Genetic Causes to Development Disorders
NCT04195490	Not specified	UNKNOWN	Evaluation of Outcomes of Feminizing Genitoplasty in Children With Disorders of Sex Development
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04717349	Not specified	RECRUITING	Data Collection Study of Pediatric and Adolescent Gynecology Conditions
NCT05058781	Not specified	RECRUITING	Minipuberty in Infants Born With Potential Hypogonadism Hypogonadotrope
NCT06692049	Not specified	RECRUITING	Gonadal Tissue Cryopreservation for Fertility Preservation in Children with a Disorder of Sex Development
NCT06989593	Not specified	RECRUITING	Breaking Silence Through Story: A Narrative Medicine Intervention for Parents of Children With Urogenital Conditions