GPR6

protein-coding

G protein-coupled receptor 6, the group of G protein-coupled receptors, Class A orphans

Gene summary

Predicted to enable sphingosine-1-phosphate receptor activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway. Predicted to act upstream of or within positive regulation of cytosolic calcium ion concentration. Predicted to be located in membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_005284.5

Inheritance

—

ClinVar variants

U:48B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr6:109,978,256-109,980,720

External References & Databases

Ensembl (ENSG00000146360)

Transcript & Mutation Effects

hg38 • Region Span ~2.5 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 GPR6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005284.5. 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			48 clinvar	1 clinvar		49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	48	1	1	50

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005284.5	RefSeq	NP_005275.1	1	MANE Select
ENST00000275169.5	Ensembl	ENSP00000275169.3	1	MANE Select
NM_001286099.2	RefSeq	NP_001273028.1	2	Standard
ENST00000414000.3	Ensembl	ENSP00000406986.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

GPCRs, Class A Rhodopsin-like

Biological Process

sphingosine-1-phosphate receptor signaling pathway
G protein-coupled receptor signaling pathway
positive regulation of cytosolic calcium ion concentration

Molecular Function

G protein-coupled receptor activity
sphingosine-1-phosphate receptor activity

Cellular Component

integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000275169
Coding exons: 1
Length: 2408
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.994	190	233	0.817	0.0000139	2248
Missense (PolyPhen)		64	107.2	0.59701		1106
Synonymous	-0.352	121	116	1.04	0.00000765	877
Loss of Function	1.63	3	7.94	0.378	3.45e-7	80

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan receptor with constitutive G(s) signaling activity that activate cyclic AMP. Promotes neurite outgrowth and blocks myelin inhibition in neurons (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.0457
RVIS EVS: 0.08
RVIS percentile EVS: 60.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.354

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium