GPR156

Chr 3AR

G protein-coupled receptor 156

Also known as: DFNB121, GABABL, PGR28

NCBI Gene: 165829 ENSG00000175697 UniProt: Q8NFN8 OMIM: 610464

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 121MIM #620551

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Deafness, autosomal recessive 121; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.03

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.03LOEUF

pLI 0.000

Z-score 1.40

OE 0.73 (0.52–1.03)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.04Z-score

OE missense 0.86 (0.79–0.94)

382 obs / 443.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.73 (0.52–1.03)

0≤0.351.4

Missense OE?0.86 (0.79–0.94)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 23 / 31.5Missense obs/exp: 382 / 443.6Syn Z: 0.63

Background carrier burden — how many people carry a rare variant somewhere in GPR156?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 39

947 rare PASS variants

Rare truncating (LoF)

1 in 630

138 rare PASS variants

Rare synonymous (reference)

1 in 150

407 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPR156. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 69	1 in 610
South Asian	~43k	1 in 56	1 in 510
Remaining (unassigned)	~30k	1 in 40	1 in 840
European (Finnish)	~27k	1 in 150	1 in 2,400
Admixed American	~22k	1 in 35	1 in 3,200
African / African American	~21k	1 in 45	1 in 710
East Asian	~20k	1 in 71	1 in 1,100
Ashkenazi Jewish	~13k	1 in 190	none seen
Middle Eastern	~2,884	1 in 41	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓