GPR158

protein-coding

G protein-coupled receptor 158, the group of G protein-coupled receptors, Class C orphans

Gene summary

Enables G protein-coupled glycine receptor activity and enzyme activator activity. Involved in G protein-coupled receptor signaling pathway; protein localization to plasma membrane; and regulation of G protein-coupled receptor signaling pathway. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_020752.3

Inheritance

—

ClinVar variants

U:174B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr10:25,174,802-25,602,229

External References & Databases

Ensembl (ENSG00000151025)

Transcript & Mutation Effects

hg38 • Region Span ~427.4 kb

Loading mutation effect viewer...

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 GPR158 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 175

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020752.3. 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	2 clinvar		3
missense			171 clinvar	6 clinvar		177
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	174	8	0	182

Loading ClinVar variants...

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_020752.3	RefSeq	NP_065803.2	11	MANE Select
ENST00000376351.4	Ensembl	ENSP00000365529.3	11	MANE Select
ENST00000650135.1	Ensembl	ENSP00000498176.1	11	Standard
ENST00000650135.2	Ensembl	ENSP00000498176.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

G protein-coupled receptor signaling pathway
protein localization to plasma membrane

Molecular Function

G protein-coupled receptor activity

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376351
Coding exons: 11
Length: 427165
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125748
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.377	645	672	0.959	0.0000357	7885
Missense (PolyPhen)		116	157.56	0.73624		1856
Synonymous	0.115	263	265	0.991	0.0000143	2442
Loss of Function	4.63	16	52.0	0.307	0.00000304	587

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan receptor.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.225
RVIS EVS: -0.41
RVIS percentile EVS: 25.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.885

Gene Damage Prediction

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