GAS2

Chr 11AR

growth arrest specific 2

Also known as: DFNB125, GAS-2

NCBI Gene: 2620 ENSG00000148935 UniProt: O43903 OMIM: 602835

The GAS2 protein is required to maintain microtubule bundles in inner ear supporting cells, providing mechanical stiffness necessary for sound transmission through the cochlea. Mutations cause autosomal recessive nonsyndromic hearing loss, with this gene being relatively tolerant to loss-of-function variants based on population constraint metrics. A GeneReviews entry is available for additional clinical guidance.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes during apoptosis. It can also modulate cell susceptibility to p53-dependent apoptosis by inhibiting calpain activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 125MIM #620877

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.81

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — GAS2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.001

Z-score 2.15

OE 0.45 (0.26–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.44Z-score

OE missense 0.91 (0.79–1.03)

154 obs / 170.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.26–0.81)

0≤0.351.4

Missense OE?0.91 (0.79–1.03)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 8 / 17.8Missense obs/exp: 154 / 170.2Syn Z: 0.16

Background carrier burden — how many people carry a rare variant somewhere in GAS2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

362 rare PASS variants

Rare truncating (LoF)

1 in 5,300

51 rare PASS variants

Rare synonymous (reference)

1 in 650

152 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GAS2. 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 340	1 in 5,400
South Asian	~43k	1 in 170	1 in 4,700
Remaining (unassigned)	~30k	1 in 300	≈ 1 in 7,500
European (Finnish)	~27k	1 in 950	1 in 3,800
Admixed American	~22k	1 in 270	≈ 1 in 5,600
African / African American	~21k	1 in 150	none seen
East Asian	~20k	1 in 240	1 in 1,900
Ashkenazi Jewish	~13k	1 in 570	1 in 1,700
Middle Eastern	~2,884	1 in 240	none seen

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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓