GAS6

Chr 13

growth arrest specific 6

Also known as: AXLLG, AXSF

The protein encoded by this gene is a ligand for tyrosine-protein kinase receptors (AXL, TYRO3, and MER) that regulates cell growth, survival, adhesion, and migration processes including endothelial cell survival, natural killer cell development, hepatic regeneration, neuron survival and migration, and platelet activation. Mutations in GAS6 cause autosomal recessive thrombophilia due to protein S deficiency-like syndrome, characterized by increased risk of venous thromboembolism. The gene shows high constraint against loss-of-function variants (LOEUF 0.486), indicating that complete loss of protein function is likely deleterious.

Summary from RefSeq, UniProt
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0
Active trials
138
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.49
LOEUF
DN
Mechanism· predicted
Clinical SummaryGAS6
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.034
Z-score 3.80
OE 0.28 (0.170.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.19Z-score
OE missense 0.83 (0.760.91)
344 obs / 412.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.170.49)
00.351.4
Missense OE0.83 (0.760.91)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 9 / 32.3Missense obs/exp: 344 / 412.1Syn Z: -0.10
DN
0.6356th %ile
GOF
0.6149th %ile
LOF
0.2776th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

GAS6 · protein map & ClinVar variants

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

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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