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.

GeneReviews 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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Lung cancer, susceptibility to}MIM #211980

ADSomatic

Autoimmune lymphoproliferative syndrome, type IBMIM #601859

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · autoimmune lymphoproliferative syndrome type 1 · AR · ClinGen 2024

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.72

LOEUF

Mechanism· predicted

📖

GeneReview available — FASLG

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?

0.72LOEUF

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

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

328 rare PASS variants

Rare truncating (LoF)

1 in 11,000

19 rare PASS variants

Rare synonymous (reference)

1 in 250

137 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FASLG. 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 240	1 in 16,000
South Asian	~43k	1 in 180	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 190	1 in 3,800
European (Finnish)	~27k	1 in 3,300	≈ 1 in 27,000
Admixed American	~22k	1 in 310	≈ 1 in 22,000
African / African American	~21k	1 in 200	none seen
East Asian	~20k	1 in 180	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 420	1 in 520
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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓