GPRC6A

protein-coding

G protein-coupled receptor class C group 6 member A, the group of Calcium sensing receptors

Gene summary

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]).[supplied by OMIM, Nov 2010]

MANE transcript

NM_148963.4

Inheritance

—

ClinVar variants

U:124B:12

Top phenotype

Disorder of sexual differentiation

gnomAD constraint

pLI —, LoF o/e 0.94

Max pathogenic AF

—

Genomic locus

chr6:116,792,085-116,829,083

External References & Databases

Ensembl (ENSG00000173612)

Transcript & Mutation Effects

hg38 • Region Span ~37.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPRC6A variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 131

not providedTotal: 3

Disorder of sexual differentiationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_148963.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			124 clinvar	10 clinvar	1 clinvar	135
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	124	11	1	136

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_148963.4	RefSeq	NP_683766.2	6	MANE Select
ENST00000310357.8	Ensembl	ENSP00000309493.4	6	MANE Select
NM_001286354.1	RefSeq	NP_001273283.1	6	Standard
NM_001286355.1	RefSeq	NP_001273284.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NOD-like receptor signaling pathway - Homo sapiens (human)
Signaling by GPCR
Signal Transduction
Class C/3 (Metabotropic glutamate/pheromone receptors)
GPCR ligand binding

Biological Process

G protein-coupled receptor signaling pathway
calcium-mediated signaling
response to amino acid

Molecular Function

G protein-coupled receptor activity
signaling receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310357
Coding exons: 6
Length: 36953
Individuals with no LoFs: 115837
Homozygous LoFs: 1439
Heterozygous LoFs: 8464
Defined: 125740
p: 0.0402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.178	473	484	0.977	0.0000225	6151
Missense (PolyPhen)		129	131.07	0.9842		1745
Synonymous	0.423	163	170	0.959	0.00000811	1749
Loss of Function	0.301	26	27.7	0.938	0.00000127	374

Population LoF Frequency

Population	CAF	p-value	Status
African	0.44	0.13	notable
Latino/Admixed American	0.20	0.079	notable
Ashkenazi Jewish	0.083	0.039	notable
East Asian	0.0052	0.0035	notable
Finnish	0.11	0.049	notable
European (Non-Finnish)	0.055	0.026	notable
South Asian	0.043	0.021	notable
Other	0.074	0.033	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor 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+). Activated by extracellular calcium and osteocalcin. Seems to act through a G(q)/G(11) and G(i)-coupled pathway. 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. {ECO:0000269|PubMed:15576628, ECO:0000269|PubMed:20947496}.;

Recessive Scores

pRec: 0.0994

Intolerance Scores

LoFtool: 0.135
RVIS EVS: 1.63
RVIS percentile EVS: 96.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0298

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High