FASLG

Chr 1ADSomatic

Fas ligand

Also known as: ALPS1B, APT1LG1, APTL, CD178, CD95-L, CD95L, FASL, TNFSF6

NCBI Gene: 356 ENSG00000117560 UniProt: P48023 OMIM: 134638

The encoded transmembrane protein is a cytokine that binds to the FAS receptor to induce apoptosis and is essential for immune system regulation, including activation-induced cell death of T cells and cytotoxic T lymphocyte-mediated apoptosis. Mutations cause autoimmune lymphoproliferative syndrome type IB, characterized by defective lymphocyte apoptosis leading to lymphadenopathy, splenomegaly, and autoimmune manifestations. The condition follows autosomal dominant inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the tumor necrosis factor superfamily. The primary function of the encoded transmembrane protein is the induction of apoptosis triggered by binding to FAS. The FAS/FASLG signaling pathway is essential for immune system regulation, including activation-induced cell death (AICD) of T cells and cytotoxic T lymphocyte induced cell death. It has also been implicated in the progression of several cancers. Defects in this gene may be related to some cases of systemic lupus erythematosus (SLE). Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2014]

OMIM ResearchGenerating clinical summary…

DNmechanismAD/SomaticLOEUF 0.722 OMIM phenotypes

Clinical Summary— FASLG

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Gene-Disease Validity (ClinGen)

autoimmune lymphoproliferative syndrome type 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.183

Z-score 2.20

OE 0.28 (0.13–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.58Z-score

OE missense 0.87 (0.76–1.00)

135 obs / 155.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.13–0.72)

0≤0.351.4

Missense OE?0.87 (0.76–1.00)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 3 / 10.8Missense obs/exp: 135 / 155.2Syn Z: -0.25

This gene — mechanism propensity

0.7228th %ile

GOF

0.5660th %ile

LOF

0.3842th %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.