GAS2

Chr 11AR

growth arrest specific 2

Also known as: DFNB125, GAS-2

NCBI Gene: 2620ENSG00000148935UniProt: O43903

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]

Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 125MIM #620877
AR
75
ClinVar variants
21
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GAS2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 50 VUS of 75 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.81LOEUF
pLI 0.001
Z-score 2.15
OE 0.45 (0.26–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.44Z-score
OE missense 0.91 (0.79–1.03)
154 obs / 170.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.45 (0.26–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.79–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 8 / 17.8Missense obs/exp: 154 / 170.2Syn Z: 0.16

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic1
VUS50
Likely Benign1
Benign3
20
Pathogenic
1
Likely Pathogenic
50
VUS
1
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
19
0
20
Likely Pathogenic
0
1
0
0
1
VUS
0
31
19
0
50
Likely Benign
0
0
1
0
1
Benign
0
0
2
1
3
Total13241175

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GAS2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Deafness, autosomal recessive 125

MIM #620877

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — GAS2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A clinical and genotype-phenotype analysis of MACF1 variants.
Dekker J et al.·Am J Hum Genet
2025
A novel variant in GAS2 is associated with autosomal dominant nonsyndromic hearing impairment in a Chinese family.
Zhang L et al.·Hum Genomics
2024
GAS2-Calpain2 axis contributes to the growth of leukemic cells.
Sun L et al.·Acta Biochim Biophys Sin (Shanghai)
2015
Integrative analysis regarding the correlation between GAS2 family genes and human glioma prognosis.
Zhao C et al.·Cancer Med
2021
Truncated HBx-dependent silencing of GAS2 promotes hepatocarcinogenesis through deregulation of cell cycle, senescence and p53-mediated apoptosis.
Zhu R et al.·J Pathol
2015
Upregulation of the growth arrest-specific-2 in recurrent colorectal cancers, and its susceptibility to chemotherapy in a model cell system.
Huang CJ et al.·Biochim Biophys Acta
2016Functional
Myogenic IGFBP5 levels in rhabdomyosarcoma are nourished by mesenchymal stromal cells and regulate growth arrest and apoptosis.
Zhang Y et al.·Cell Commun Signal
2025
A prognostic signature consisting of metabolism-related genes and SLC17A4 serves as a potential biomarker of immunotherapeutic prediction in prostate cancer.
Li H et al.·Front Immunol
2022
Insights into the immune manipulation mechanisms of pollen allergens by protein domain profiling.
Patel S et al.·Comput Biol Chem
2017Functional
Molecular profiling of CD34+ cells in idiopathic myelofibrosis identifies a set of disease-associated genes and reveals the clinical significance of Wilms' tumor gene 1 (WT1).
Guglielmelli P et al.·Stem Cells
2007
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools