GPR156

protein-coding

G protein-coupled receptor 156, the group of G protein-coupled receptors, Class C orphans

Gene summary

G protein-coupled receptors (GPCRs) are a large superfamily of cell surface receptors characterized by 7 helical transmembrane domains, together with N-terminal extracellular and C-terminal intracellular domains.[supplied by OMIM, Mar 2008]

MANE transcript

NM_153002.3

Inheritance

ClinVar variants

P:5U:119B:18

Top phenotype

Deafness, autosomal recessive 121

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr3:120,164,645-120,285,222

External References & Databases

Ensembl (ENSG00000175697)

Transcript & Mutation Effects

hg38 • Region Span ~120.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hearing loss, autosomal recessive 121STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957825

Submitter: PanelApp Australia

hearing loss, autosomal recessive 121MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957825

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 121AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 36928819; 37814107

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPR156 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 124

GPR156-related disorderTotal: 10

Hearing loss, autosomal recessive 121Total: 5

Hearing loss, autosomal recessiveTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153002.3. 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	1 clinvar	2 clinvar		4
missense			117 clinvar	16 clinvar		133
nonsense			1 clinvar			1
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)		2 clinvar				2
Total	0	5	119	18	0	142

Highest pathogenic variant AF is 0.00000273715

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153002.3	RefSeq	NP_694547.2	9	MANE Select
ENST00000464295.6	Ensembl	ENSP00000417261.1	9	MANE Select
NM_001168271.2	RefSeq	NP_001161743.1	9	Standard
ENST00000461057.1	Ensembl	ENSP00000418758.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuroactive ligand-receptor interaction - Homo sapiens (human)

Biological Process

gamma-aminobutyric acid signaling pathway

Molecular Function

G protein-coupled GABA receptor activity

Cellular Component

plasma membrane
G protein-coupled receptor heterodimeric complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000464295
Coding exons: 9
Length: 120450
Individuals with no LoFs: 125615
Homozygous LoFs: 0
Heterozygous LoFs: 133
Defined: 125748
p: 0.000529

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	382	444	0.861	0.0000232	5283
Missense (PolyPhen)		114	138.96	0.8204		1800
Synonymous	0.628	167	178	0.940	0.00000920	1686
Loss of Function	1.40	23	31.5	0.730	0.00000153	371

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00075	0.00074	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00066	0.00066	rare
South Asian	0.0010	0.0010	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan receptor.;

Recessive Scores

pRec: 0.0767

Intolerance Scores

LoFtool: 0.393
RVIS EVS: 1.4
RVIS percentile EVS: 94.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.299

Gene Damage Prediction

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