FAS

Chr 10

Fas cell surface death receptor

Also known as: ALPS1A, APO-1, APT1, CD95, FAS1, FASTM, TNFRSF6

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. It has been shown to play a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells. Several alternatively spliced transcript variants have been described, some of which are candidates for nonsense-mediated mRNA decay (NMD). The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform. [provided by RefSeq, Mar 2011]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAutoimmune lymphoproliferative syndrome 1A

Clinical highlights

Gene-disease validity (ClinGen)
FAS-related autoimmune lymphoproliferative immune disorder · SDDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
A dominant-negative effect is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
2517
Pubs (1 yr)
P/LP submissions
P/LP missense
0.44
LOEUF
DN
Mechanism· G2P
📖
GeneReview available — FAS
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.44LOEUF
pLI 0.812
Z-score 3.01
OE 0.14 (0.060.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.23Z-score
OE missense 0.73 (0.630.85)
121 obs / 165.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.14 (0.060.44)
00.351.4
Missense OE?0.73 (0.630.85)
00.61.4
Synonymous OE?0.93
01.21.6
LoF obs/exp: 2 / 14.3Missense obs/exp: 121 / 165.6Syn Z: 0.40

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FAS · 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

Neovascular Age-Related Macular Degeneration (nAMD)

Single Intravitreal (IVT) Injection of 4D-150 in Patients With Macular Neovascularization Secondary to Age-Related Macular Degeneration

RECRUITING
NCT07064759Phase PHASE34D Molecular TherapeuticsStarted 2025-07-22
4D-150 IVT (3E10 vg/eye)EYLEA® (aflibercept) Injection 2 mg (0.05mL)
Breast Cancer

Anti-Inflammatory Diet in BRC Patients on Aromatase Inhibitors

RECRUITING
NCT06214598Phase NAUniversity of BelgradeStarted 2024-03-01
SupplementAI dietPlacebo
Autoimmune Lymphoproliferative Syndrome

Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients

RECRUITING
NCT06730126Phase PHASE2National Institute of Allergy and Infectious Diseases (NIAID)Started 2025-03-10
Soquelitinib
Biliary Tract CancerColorectal CarcinomaGastric Cancer, Metastatic

CDH17 CAR-T Therapy in Advanced Malignant Solid Tumors

RECRUITING
NCT06937567Phase EARLY_PHASE1Zhejiang UniversityStarted 2024-12-26
CDH17 CAR-TFAST LACO-Stim CDH17 CAR-T
Obesity & OverweightCardiometabolic Health IndicatorsAddiction

Tirzepatide Impact Assessment Study

RECRUITING
NCT07740291Phase NATexas Tech UniversityStarted 2025-01-02
GLP-1 Receptor Agonist TherapyStructured Lifestyle Intervention
Solid Tumors Harboring NTRK Fusion

A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children

ACTIVE NOT RECRUITING
NCT02637687Phase PHASE1, PHASE2BayerStarted 2015-12-16
Larotrectinib (Vitrakvi, BAY2757556)
ResilienceCognitive Function and Well-BeingMuscle Function, Handgrip Strength Test

Aging Resilience Through Microbiota Optimization and Regulation

ACTIVE NOT RECRUITING
NCT06649981Phase PHASE1Gonzalo Jorquera, PhDStarted 2025-01-10
FMT capsulePlacebo Capsule(s)
NSCLC (Advanced Non-small Cell Lung Cancer)

Becotatug Vedotin Combined With Pucotenlimab ± Radiotherapy as First-Line Treatment for Driver-Gene-Negative, EGFR-Expression-Positive Advanced Non-Small Cell Lung Cancer

NOT YET RECRUITING
NCT07627321Phase PHASE2Anhui Provincial Cancer HospitalStarted 2026-07-15
PucotenlimabBecotatug vedotinRadiotherapy
Alzheimer DiseaseAlzheimer Dementia

Daily Light and Sound Stimulation to Improve Brain Functions in Alzheimer's Disease

ACTIVE NOT RECRUITING
NCT04055376Phase NAMassachusetts Institute of TechnologyStarted 2019-08-14
GENUS device (Active Settings)GENUS device (Sham Settings)
HIV-1-infection

DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection

RECRUITING
NCT06203132Phase PHASE3ANRS, Emerging Infectious DiseasesStarted 2025-01-27
Doravirine + tenofovir DF + lamivudineDolutegravir + tenofovir DF + lamivudine or emtricitabine
HER2-negative Breast Cancer

Neoadjuvant Concomitant Modulated Electro-hyperthermia in HER2-negative Breast Cancer

ACTIVE NOT RECRUITING
NCT05889390Phase PHASE2, PHASE3Semmelweis UniversityStarted 2023-02-20
Oncotherm EHY-2030PaclitaxelCarboplatin
Cardiovascular Disease

Genes, Omega-3 Fatty Acids and Cardiovascular Disease Risk Factors

ACTIVE NOT RECRUITING
NCT01343342Phase NALaval UniversityStarted 2009-10
n-3 PUFA supplementation