The GAS1 protein functions as a growth suppressor that blocks cell cycle entry into S phase and prevents cycling of normal and transformed cells. Mutations in GAS1 cause autosomal recessive holoprosencephaly, likely through loss of this growth suppressive function. The gene shows constraint against loss-of-function variants (pLI 0.82, LOEUF 0.53), consistent with pathogenic variants causing recessive disease through loss of protein function.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.53
Clinical SummaryGAS1
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Gene-Disease Validity (ClinGen)
holoprosencephaly · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.819
Z-score 2.20
OE 0.00 (0.000.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.75Z-score
OE missense 0.82 (0.700.96)
110 obs / 134.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.53)
00.351.4
Missense OE0.82 (0.700.96)
00.61.4
Synonymous OE1.56
01.21.6
LoF obs/exp: 0 / 5.6Missense obs/exp: 110 / 134.4Syn Z: -3.42

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GAS1 · 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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