GPR156

Chr 3AR

G protein-coupled receptor 156

Also known as: DFNB121, GABABL, PGR28

This orphan G-protein coupled receptor regulates hair cell orientation in the inner ear mechanosensory organs, specifically triggering 180-degree reversals in hair cell polarity to create the line of polarity reversal across which stereociliary bundles are arranged in opposite orientations. Mutations cause autosomal recessive deafness, typically presenting as congenital hearing loss. The gene shows very low constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismARLOEUF 1.031 OMIM phenotype
Clinical SummaryGPR156
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.000
Z-score 1.40
OE 0.73 (0.521.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.04Z-score
OE missense 0.86 (0.790.94)
382 obs / 443.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.73 (0.521.03)
00.351.4
Missense OE0.86 (0.790.94)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 23 / 31.5Missense obs/exp: 382 / 443.6Syn Z: 0.63
DN
0.7033th %ile
GOF
0.74top 25%
LOF
0.3745th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GPR156 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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