FASLG

Summary

FASLG (Fas ligand, HGNC:11936) is a protein-coding gene on chromosome 1q24.3, encoding Tumor necrosis factor ligand superfamily member 6 (P48023). Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells.

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.

Source: NCBI Gene 356 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoimmune lymphoproliferative syndrome type 1 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 24
• Clinical variants (ClinVar): 241 total — 4 pathogenic, 3 likely-pathogenic
• GTEx eGene: eQTL in 6 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 85
• Drug target: yes — 1 curated mechanism-of-action drug
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.77 (intermediate), LOEUF 0.61 (unconstrained)
• MANE Select transcript: NM_000639
• Interaction hub: 3,452 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11936
Approved symbol	FASLG
Name	Fas ligand
Location	1q24.3
Locus type	gene with protein product
Status	Approved
Aliases	APTL, CD95L, FasL, CD178
Ensembl gene	ENSG00000117560
Ensembl biotype	protein_coding
OMIM	134638
Entrez	356

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

MANE Select: ENST00000367721

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000367721, ENST00000340030, ENST00000875216, ENST00001145550

RefSeq mRNA: 2 — MANE Select: NM_000639 NM_000639, NM_001302746

CCDS: CCDS1304, CCDS76243

Canonical transcript exons

ENST00000367721 — 4 exons

Exon	Start	End
ENSE00000789865	172660095	172660140
ENSE00001909404	172659103	172659549
ENSE00003504329	172665622	172666876
ENSE00003669847	172664334	172664390

Expression profiles

Bgee: expression breadth ubiquitous, 118 present calls, max score 88.16.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.2531 / max 1181.6431, expressed in 121 samples.

Highest expression (Bgee): granulocyte, blood, lymph node, spleen, amniotic fluid.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FASLG is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Visceral Omentum	eqtl	5.4e-03	-0.19	1:172840493:G:A
Brain Substantia nigra	eqtl	1.3e-02	+0.56	1:173505928:A:AAAAC
Spleen	eqtl	2.3e-02	+0.23	1:172705401:C:T
Nerve Tibial	eqtl	2.7e-02	-0.59	1:172707046:T:C
Skin Not Sun Exposed Suprapubic	eqtl	3.9e-02	+0.89	1:173202717:C:T
Esophagus Gastroesophageal Junction	eqtl	4.1e-02	+0.97	1:173181923:C:T

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
6705	1.0025	88
6702	0.1402	45
6703	0.0663	32
6704	0.0441	23

Top tissues by expression

showing 100 of 265 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	88.16	gold quality
blood	UBERON:0000178	71.52	gold quality
lymph node	UBERON:0000029	69.58	gold quality
spleen	UBERON:0002106	68.81	gold quality
amniotic fluid	UBERON:0000173	66.40	silver quality
jejunal mucosa	UBERON:0000399	64.92	silver quality
ileal mucosa	UBERON:0000331	64.51	gold quality
cervix squamous epithelium	UBERON:0006922	64.07	gold quality
gall bladder	UBERON:0002110	62.50	gold quality
duodenum	UBERON:0002114	62.09	gold quality
palpebral conjunctiva	UBERON:0001812	61.79	gold quality
tibialis anterior	UBERON:0001385	60.32	silver quality
rectum	UBERON:0001052	59.95	gold quality
bone marrow	UBERON:0002371	59.72	gold quality
germinal epithelium of ovary	UBERON:0001304	58.94	gold quality
vermiform appendix	UBERON:0001154	58.71	gold quality
mucosa of transverse colon	UBERON:0004991	58.49	gold quality
squamous epithelium	UBERON:0006914	57.65	gold quality
right lobe of liver	UBERON:0001114	57.53	gold quality
pancreatic ductal cell	CL:0002079	57.30	silver quality
caecum	UBERON:0001153	56.74	gold quality
endothelial cell	CL:0000115	56.61	gold quality
decidua	UBERON:0002450	56.55	gold quality
esophagus squamous epithelium	UBERON:0006920	56.40	gold quality
pleura	UBERON:0000977	56.18	gold quality
epithelium of esophagus	UBERON:0001976	56.01	gold quality
parietal pleura	UBERON:0002400	55.46	gold quality
leukocyte	CL:0000738	54.95	gold quality
bone marrow cell	CL:0002092	54.89	gold quality
visceral pleura	UBERON:0002401	54.88	gold quality
gingival epithelium	UBERON:0001949	54.78	gold quality
tonsil	UBERON:0002372	54.61	gold quality
endometrium	UBERON:0001295	54.16	gold quality
liver	UBERON:0002107	53.48	gold quality
epithelium of nasopharynx	UBERON:0001951	53.45	gold quality
deltoid	UBERON:0001476	53.38	silver quality
gingiva	UBERON:0001828	53.18	gold quality
cranial nerve II	UBERON:0000941	53.05	silver quality
smooth muscle tissue	UBERON:0001135	53.03	gold quality
right coronary artery	UBERON:0001625	53.00	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
cervix epithelium	UBERON:0004801	52.42	gold quality
mononuclear cell	CL:0000842	51.95	gold quality
monocyte	CL:0000576	51.39	gold quality
oviduct epithelium	UBERON:0004804	51.18	gold quality
epithelial cell of pancreas	CL:0000083	50.73	gold quality
quadriceps femoris	UBERON:0001377	50.73	gold quality
small intestine	UBERON:0002108	50.73	gold quality
colonic epithelium	UBERON:0000397	50.70	gold quality
lung	UBERON:0002048	50.56	gold quality
trabecular bone tissue	UBERON:0002483	50.45	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
thymus	UBERON:0002370	50.38	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
upper lobe of left lung	UBERON:0008952	50.22	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
mammalian vulva	UBERON:0000997	49.94	gold quality
vastus lateralis	UBERON:0001379	49.64	gold quality
upper lobe of lung	UBERON:0008948	49.35	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
fallopian tube	UBERON:0003889	48.80	gold quality
small intestine Peyer’s patch	UBERON:0003454	48.71	gold quality
muscle tissue	UBERON:0002385	48.60	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
nasal cavity epithelium	UBERON:0005384	48.14	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality
urinary bladder	UBERON:0001255	47.71	gold quality
renal glomerulus	UBERON:0000074	47.60	gold quality
layer of synovial tissue	UBERON:0007616	47.54	gold quality
uterus	UBERON:0000995	47.46	gold quality
kidney epithelium	UBERON:0004819	47.32	gold quality
nasal cavity mucosa	UBERON:0001826	47.23	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
right uterine tube	UBERON:0001302	47.10	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
cortex of kidney	UBERON:0001225	46.97	gold quality
skeletal muscle tissue	UBERON:0001134	46.94	gold quality
placenta	UBERON:0001987	46.90	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
upper leg skin	UBERON:0004262	45.84	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	45.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	45.49	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
body of stomach	UBERON:0001161	45.30	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.68
E-HCAD-29	no	763.58

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 71 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Lymph node	tissue	5.3	low
Spleen	tissue	3.7	not detected
Bone marrow	tissue	2.7	medium
Olfactory bulb	tissue	2.1
Cerebellum	tissue	1.9	low
Cerebral cortex	tissue	1.8	low
Lung	tissue	1.8	not detected
Insular cortex	tissue	1.8
Duodenum	tissue	1.7	low
Tonsil	tissue	1.7	low
Hippocampal formation	tissue	1.7
Entorhinal cortex	tissue	1.7
Retrosplenial cortex	tissue	1.7
Retrosplenial and cingulate cortex	tissue	1.6
Prefrontal cortex	tissue	1.5
Motor cortex	tissue	1.5
Basal ganglia	tissue	1.5	low
Amygdala	tissue	1.5
Corpus callosum	tissue	1.5
Temporal cortex	tissue	1.5
Occipital cortex	tissue	1.5
Stomach 1	tissue	1.4	low
Small intestine	tissue	1.3	low
Postcentral gyrus	tissue	1.3
Somatosensory cortex	tissue	1.3
Ventral forebrain	tissue	1.2
Liver	tissue	1.1	not detected
Gallbladder	tissue	1.1	not detected
Septum	tissue	1.1
Putamen	tissue	1.0
Substantia nigra	tissue	1.0
Periaqueductal gray	tissue	1.0
Salivary gland	tissue	0.9	not detected
Choroid plexus	tissue	0.9
Medulla oblongata	tissue	0.9
Hypothalamus	tissue	0.9
Spinal cord	tissue	0.9
Appendix	tissue	0.9	low
Pons	tissue	0.8
Rectum	tissue	0.8	not detected
Nucleus accumbens	tissue	0.8
Midbrain	tissue	0.8
Thalamus	tissue	0.8
Locus coeruleus	tissue	0.8
Colon	tissue	0.7	not detected
Urinary bladder	tissue	0.7	not detected
Hippocampus	tissue	0.7	low
Adrenal gland	tissue	0.7	not detected
Epididymis	tissue	0.6	low
Superior colliculi	tissue	0.6
Thymus	tissue	0.6
Breast	tissue	0.5	not detected
Endometrium 1	tissue	0.5	not detected
Prostate	tissue	0.5	not detected
Cervix	tissue	0.4	not detected
Skin 1	tissue	0.3	not detected
Heart muscle	tissue	0.3	not detected
Seminal vesicle	tissue	0.3	not detected
Adipose tissue	tissue	0.3	not detected
Esophagus	tissue	0.3	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Somatomor cortex, precentral gyrus (white matter) (1.5), White matter (1.5), Median raphe nucleus (1.4), Nucleus gracilis (1.4), Ventral hippocampus (1.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ATF2, CEBPB, CIITA, CREM, EGR1, EGR2, EGR3, ELF4, ESR1, ESR2, ETS1, FOS, FOSB, FOXO1, FOXO3, FOXP3, FOXS1, GATA6, HBP1, HSF1, IRF1, IRF2, JUN, LEF1, MAX, MTA1, MYC, MYCN, NFATC1, NFATC2, NFATC3, NFKB1, NFKB, NFKBID, NR3C1, NR4A1, PAX1

miRNA regulators (miRDB)

Targeting FASLG by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 57 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-586	99.65	70.40	2051

Functional genomics

gnomAD constraint: pLI 0.767, LOEUF 0.606, missense Z 1.1 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000367721 — one region, missense o/e 0.89. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Mouse cells expressing human membrane-bound, but not soluble, Fas ligand induce inflammation in vivo. (PMID:11500835)
• Expression of FasL gene in T cells of renal allograft recipients (PMID:11716959)
• Differential secretion of Fas ligand microvesicles during activation-induced death of T cells (PMID:11739488)
• Induction of FasL expression by adhesion of endometrial stromal cells to the extracellular matrix may take part in the development of immunotolerance by inducing apoptosis of cytotoxic T lymphocytes (PMID:11751256)
• Western blot analysis showed that butyrate increased Fas and Fas ligand levels in butyrate-induced apoptosis. (PMID:11786482)
• Expression of Fas and Fas ligand in esophageal tissue mucosa and carcinomas (PMID:11788891)
• A minimal region of the fasL promoter has been identified containing the transcription start site and a noncanonical c-Myc-binding element, which mediates fasL promoter repression by the activated vitamin D3 receptor in T lymphocytes. (PMID:11801650)
• expression was found mainly on astrocytes and microglial cells; no significant difference between cases with and without pontosubicular neuron necrosis (PMID:11809905)
• Up-regulation in highly malignant multiple myeloma plasma cells negatively regulates erythroblast maturation; a major pathogenetic mechanism of anemia in multiple myeloma. (PMID:11830480)
• evaluation of the FasL gene FASL on chromosome 1q23 as a candidate susceptibility gene for Type I diabetes (PMID:11845233)
• The results indicate that FasL inhibition by all-trans-RA involves a novel mechanism whereby the transcriptional function of NFAT is blocked. (PMID:11856352)
• Fas/FasL pathway can be employed by monocytes/macrophages to induce VSMC apoptosis in the atherosclerotic lesions. (PMID:11882326)
• upregulation of Fas by IFN-gamma in SNU-638 may accelerate the apoptosis pathway through the Fas and FasL interaction between gastric cancer cells and immune cells (PMID:11895550)
• physiological function of human sFasL is to delete the potentially auto-reactive “memory” lymphocytes (PMID:11908702)
• HIV Tat binds Egr proteins and enhances Egr-dependent transactivation of the Fas ligand promoter (PMID:11909874)
• FasL protein is an important mediator of apoptosis. (PMID:11925103)
• Differential expressions of Fas and Fas ligand in human placenta (PMID:11961305)
• Genetic polymorphisms of FasL (CD178) in human longevity (PMID:11965496)
• The endometrial cells expressed Fas and low levels of FasL (PMID:11994542)
• expressed during acute cellular rejection episodes after kidney transplantation (PMID:12009596)
• “trophoblast-cytokine-Fas/FasL triad” determines the ability of the Fas/FasL system to regulate trophoblast viability (PMID:12021072)
• Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. (PMID:12021310)
• Abnormal expression and function of Fas ligand of lachrymal glands and peripheral blood was found in Sjogren’s syndrome patients with enlarged exocrine glands. (PMID:12100038)
• findings support the hypothesis that the expression of FasL in normal ovary is hormonally sensitive (PMID:12113885)
• the role of Fas/Fas ligand (FasL) in tum orgenesis, immune escape, counterattack in colonic cancer (PMID:12137598)
• Regulation of fas ligand expression by IL-8 in human endometrium. (PMID:12161534)
• inhibiton of CD95L expression by vitamin E (PMID:12208869)
• serum and peritoneal fluid of women with moderate to severe endometriosis contain elevated concentrations of soluble Fas ligand compared to women with minimal or mild endometriosis and women without endometriosis (PMID:12372468)
• tranduces, in synergy with non-cytotoxic anti-Fas monoclonal antibody (mAb), signals for apoptosis and nuclear translocation of the NF-kappaB (p65/p50) heterodimer (PMID:12393889)
• fas ligand is up-regulated in acute lung injury and the acute respiratory distress syndrome (PMID:12414525)
• The human papillomavirus type 16 E5 protein impairs TRAIL- and FasL-mediated apoptosis in HaCaT cells by different mechanisms. (PMID:12414956)
• T cells from systemic lupus erythematosus patients kill autologous monocytes through apoptotic pathways involving the ligand FasL. (PMID:12421989)
• In transgenic mice, the human FASL promoter induces reporter expression in intestinal epithelial cells. Non-lymphoid FasL is expressed in response to peripheral T cell activation & regulates T cells that infiltrate peripheral tissues. (PMID:12454289)
• Cleavage of FasL by MMP-7 occurs at the leucine residues in sequence “ELAELR” within the region between the transmembrane and trimerization domains. When this site is unavailable, a “SL,” is cleaved. MMP-7 differentially processes murine and human FasL (PMID:12464266)
• homeostatic regulation of myelopoiesis in bone marrow is mediated via an autoregulatory feedback loop via the Fas-FasL pathway (PMID:12482410)
• A role for the Fas/Fas ligand apoptotic pathway in regulating myeloid progenitor cell kinetics. (PMID:12482505)
• Somatostatin receptor subtype 2 sensitizes human pancreatic cancer cells to ligand-induced apoptosis (PMID:12490654)
• The Fas ligand may be involved in the apoptosis of astrocytic tumors, and the apoptotic index can be a useful parameter for assessing prognosis of astrocytic tumors. (PMID:12507389)
• expression and function of fas ligand in human myeloid leukemia cells (PMID:12513781)
• Fas-L expression may be associated with the escape from of immunal surveillance. (PMID:12515623)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	faslg	ENSDARG00000098913
mus_musculus	Fasl	ENSMUSG00000000817
rattus_norvegicus	Faslg	ENSRNOG00000002978

Paralogs (8): CD40LG (ENSG00000102245), TNFSF11 (ENSG00000120659), TNFSF10 (ENSG00000121858), TNFSF14 (ENSG00000125735), TNFSF15 (ENSG00000181634), LTA (ENSG00000226979), LTB (ENSG00000227507), TNF (ENSG00000232810)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:99255) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 85 distinct phenotype terms.

Mouse phenotype (MP)	Records
enlarged spleen	7
enlarged lymph nodes	7
premature death	5
increased IgM level	5
increased IgG level	4
increased anti-nuclear antigen antibody level	4
abnormal lymph node morphology	3
increased immunoglobulin level	3
increased IgA level	3
abnormal osteoclast physiology	2
abnormal T cell differentiation	2
glomerulonephritis	2
increased autoantibody level	2
increased anti-double stranded DNA antibody level	2
increased susceptibility to autoimmune diabetes	2
increased spleen weight	2
increased lymphocyte cell number	2
increased T cell number	2
decreased cytotoxic T cell cytolysis	2
increased IgG1 level	2
increased IgG2a level	2
increased IgG2b level	2
increased leukocyte cell number	1
increased neutrophil cell number	1
decreased granulocyte number	1

+60 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos indicus	P59684	100.0%	Diamond
Macaca nemestrina	P63306	100.0%	Diamond
Macaca mulatta	P63307	100.0%	Diamond
Macaca fascicularis	P63308	100.0%	Diamond
Bos taurus	Q06599	100.0%	Diamond
Bubalus kerabau	Q2MH05	100.0%	Diamond
Cercocebus atys	Q9BDN1	99.6%	Diamond
Capra hircus	P13296	97.9%	Diamond
Ovis aries	P23383	97.9%	Diamond
Peromyscus leucopus	P36939	90.6%	Diamond
Sus scrofa	P26445	90.2%	Diamond
Saimiri sciureus	Q8MKG8	90.1%	Diamond
Canis lupus familiaris	Q5WR07	88.7%	Diamond
Marmota monax	Q9JM09	88.3%	Diamond
Felis catus	Q861W5	87.9%	Diamond
Oryctolagus cuniculus	P10154	85.0%	Diamond
Notamacropus eugenii	Q9XT48	82.4%	Diamond
Gallus gallus	Q9I8D8	40.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SUCO	protein-coding	51430
PIGC	protein-coding	5279
C1orf105	protein-coding	92346
DNM3	protein-coding	26052

Protein

Protein identifiers

Tumor necrosis factor ligand superfamily member 6 — P48023 (reviewed: P48023)

Alternative names: Apoptosis antigen ligand, CD95 ligand, Fas antigen ligand

All UniProt accessions (2): P48023, Q53ZZ1

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells. Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development. Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses. TNFRSF6/FAS-mediated apoptosis also has a role in the induction of peripheral tolerance. Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis. Induces FAS-mediated activation of NF-kappa-B, initiating non-apoptotic signaling pathways. Can induce apoptosis but does not appear to be essential for this process. Cytoplasmic form induces gene transcription inhibition.

Subunit / interactions. Homotrimer. Interacts with ARHGAP9, BAIAP2L1, BTK, CACNB3, CACNB4, CRK, DLG2, DNMBP, DOCK4, EPS8L3, FGR, FYB1, FYN, HCK, ITK, ITSN2, KALRN, LYN, MACC1, MIA, MPP4, MYO15A, NCF1, NCK1, NCK2, NCKIPSD, OSTF1, PIK3R1, PSTPIP1, RIMBP3C, SAMSN1, SH3GL3, SH3PXD2B, SH3PXD2A, SH3RF2, SKAP2, SNX33, SNX9, SORBS3, SPTA1, SRC, SRGAP1, SRGAP2, SRGAP3, TEC, TJP3 and YES1.

Subcellular location. Cell membrane. Cytoplasmic vesicle lumen. Lysosome lumen Secreted Nucleus.

Post-translational modifications. The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form undergoes two successive intramembrane proteolytic cleavages. The first one is processed by ADAM10 producing an N-terminal fragment, which lacks the receptor-binding extracellular domain. This ADAM10-processed FasL (FasL APL) remnant form is still membrane anchored and further processed by SPPL2A that liberates the FasL intracellular domain (FasL ICD). FasL shedding by ADAM10 is a prerequisite for subsequent intramembrane cleavage by SPPL2A in T-cells. N-glycosylated. Glycosylation enhances apoptotic activity. Phosphorylated by FGR on tyrosine residues; this is required for ubiquitination and subsequent internalization. Monoubiquitinated.

Disease relevance. Autoimmune lymphoproliferative syndrome 1B (ALPS1B) [MIM:601859] A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the tumor necrosis factor family.

Isoforms (2)

UniProt ID	Names	Canonical?
P48023-1	1	yes
P48023-2	2

RefSeq proteins (2): NP_000630, NP_001289675 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006052	TNF_dom	Domain
IPR006053	TNF	Family
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR021184	TNF_CS	Conserved_site
IPR028326	FASL	Family

Pfam: PF00229

UniProt features (41 total): strand 12, chain 4, glycosylation site 3, mutagenesis site 3, helix 3, compositionally biased region 2, site 2, splice variant 2, sequence variant 2, topological domain 2, region of interest 2, disulfide bond 1, turn 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
5L19	Crystal Structure of a human FasL mutant	X-RAY DIFFRACTION	2
4MSV	Crystal structure of FASL and DcR3 complex	X-RAY DIFFRACTION	2.5
5L36	Crystal Structure of a human FasL mutant in complex with human DcR3	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48023-F1	80.46	0.56

Human Protein Atlas

Protein class: CD markers, Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted secreted proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, Potential drug targets, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2)

Position	Role
81–82	cleavage; by sppl2a
129–130	cleavage; by adam10

Disulfide bonds (1)

Type	Positions
Disulfide bond	202–233

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	184, 250, 260

Mutagenesis-validated functional residues (3)

Position	Phenotype
206	lowers binding to tnfrsf6 and reduces cytotoxicity more than 100-fold.
218	lowers binding to tnfrsf6 and abolishes cytotoxicity.
275	abolishes binding to tnrfsf6 and cytotoxicity.

Function

Pathways and Gene Ontology

Reactome pathways

10 curated (TAS) of 29; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

29 pathways:

ID	Pathway	Evidence
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models ⚕	curated
R-HSA-5218900	CASP8 activity is inhibited	curated
R-HSA-140534	Caspase activation via Death Receptors in the presence of ligand	curated
R-HSA-69416	Dimerization of procaspase-8	curated
R-HSA-9614657	FOXO-mediated transcription of cell death genes	curated
R-HSA-75157	FasL/ CD95L signaling	curated
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling	curated
R-HSA-5213460	RIPK1-mediated regulated necrosis	curated
R-HSA-3371378	Regulation by c-FLIP	curated
R-HSA-5669034	TNFs bind their physiological receptors	curated
R-HSA-9734009	Defective Intrinsic Pathway for Apoptosis ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9645723	Diseases of programmed cell death ⚕	—
R-HSA-8863678	Neurodegenerative Diseases ⚕	—
R-HSA-109581	Apoptosis	—
R-HSA-5357769	Caspase activation via extrinsic apoptotic signalling pathway	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-73887	Death Receptor Signaling	—
R-HSA-9614085	FOXO-mediated transcription	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-168256	Immune System	—
R-HSA-5357801	Programmed Cell Death	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-5218859	Regulated Necrosis	—
R-HSA-5675482	Regulation of necroptotic cell death	—
R-HSA-162582	Signal Transduction	—
R-HSA-449147	Signaling by Interleukins	—
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway	—

MSigDB gene sets: 625 (showing top): BIOCARTA_PTEN_PATHWAY, MODULE_92, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_ENDOSOME_ORGANIZATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_VESICLE_ORGANIZATION, KEGG_MAPK_SIGNALING_PATHWAY, MODULE_64, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOCC_CELL_SURFACE, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT

GO Biological Process (28): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA-templated transcription (GO:0006351), apoptotic process (GO:0006915), inflammatory cell apoptotic process (GO:0006925), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), negative regulation of angiogenesis (GO:0016525), intracellular chloride ion homeostasis (GO:0030644), response to lipopolysaccharide (GO:0032496), positive regulation of apoptotic process (GO:0043065), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of neuron apoptotic process (GO:0043525), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), endosomal lumen acidification (GO:0048388), T cell apoptotic process (GO:0070231), necroptotic process (GO:0070266), response to growth factor (GO:0070848), cellular response to type II interferon (GO:0071346), apoptotic signaling pathway (GO:0097190), extrinsic apoptotic signaling pathway (GO:0097191), necroptotic signaling pathway (GO:0097527), release of sequestered calcium ion into cytosol by endoplasmic reticulum (GO:1903514), positive regulation of phosphatidylserine exposure on apoptotic cell surface (GO:1905782), positive regulation of endothelial cell apoptotic process (GO:2000353), positive regulation of extrinsic apoptotic signaling pathway (GO:2001238), immune response (GO:0006955)

GO Molecular Function (5): signaling receptor binding (GO:0005102), death receptor binding (GO:0005123), cytokine activity (GO:0005125), tumor necrosis factor receptor binding (GO:0005164), protein binding (GO:0005515)

GO Cellular Component (12): extracellular region (GO:0005576), nucleus (GO:0005634), plasma membrane (GO:0005886), caveola (GO:0005901), cell surface (GO:0009986), lysosomal lumen (GO:0043202), perinuclear region of cytoplasm (GO:0048471), cytoplasmic vesicle lumen (GO:0060205), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Caspase activation via Death Receptors in the presence of ligand	2
Programmed Cell Death	2
Caspase activation via extrinsic apoptotic signalling pathway	1
Regulated Necrosis	1
Regulation of necroptotic cell death	1
Signaling by Interleukins	1
Death Receptor Signaling	1
Neurodegenerative Diseases	1
FOXO-mediated transcription	1
TNFR2 non-canonical NF-kB pathway	1
Immune System	1
RNA Polymerase II Transcription	1
Cytokine Signaling in Immune system	1
Apoptosis	1

GO top-level categories

showing 60 of 62 GO namespaces:

Category	Terms
cellular anatomical structure	5
apoptotic process	2
cell communication	2
signaling	2
tumor necrosis factor receptor superfamily binding	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
gene expression	1
RNA biosynthetic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
extrinsic apoptotic signaling pathway	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
intracellular monoatomic anion homeostasis	1
chloride ion homeostasis	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
positive regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
positive regulation of ERBB signaling pathway	1
endosome organization	1
intracellular pH reduction	1
lymphocyte apoptotic process	1
programmed necrotic cell death	1
response to endogenous stimulus	1
response to type II interferon	1
cellular response to cytokine stimulus	1
protein binding	1
receptor ligand activity	1
binding	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
plasma membrane raft	1
lysosome	1
vacuolar lumen	1
cytoplasmic vesicle	1
vesicle lumen	1
intracellular organelle lumen	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 46 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
T cell apoptotic process	BP	direct assay
apoptotic signaling pathway	BP	direct assay
extrinsic apoptotic signaling pathway	BP	direct assay
extrinsic apoptotic signaling pathway via death domain receptors	BP	direct assay
necroptotic process	BP	direct assay
necroptotic signaling pathway	BP	direct assay
negative regulation of angiogenesis	BP	direct assay
negative regulation of transcription by RNA polymerase II	BP	direct assay
positive regulation of apoptotic process	BP	direct assay
positive regulation of canonical NF-kappaB signal transduction	BP	expression pattern
positive regulation of endothelial cell apoptotic process	BP	direct assay
positive regulation of phosphatidylserine exposure on apoptotic cell surface	BP	direct assay
release of sequestered calcium ion into cytosol by endoplasmic reticulum	BP	direct assay
extracellular exosome	CC	direct assay
nucleus	CC	direct assay
plasma membrane	CC	direct assay
cytokine activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,452 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FASLG	CASP8	Q14790	948
FASLG	FAS	P25445	940
FASLG	FADD	Q13158	907
FASLG	GZMB	P10144	873
FASLG	CD8A	P01732	868
FASLG	CASP3	P42574	865
FASLG	PRF1	P14222	859
FASLG	CD4	P01730	854
FASLG	BCL2	P10415	849
FASLG	IFNG	P01579	844
FASLG	CASP10	Q92851	839
FASLG	CFLAR	O15519	834
FASLG	CASP9	P55211	832
FASLG	TNFRSF6B	O95407	823
FASLG	TNFRSF1A	P19438	821

IntAct

Human interaction partners of FASLG in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 78 partners by confidence:

Partner	Interaction type	MIscore	Records
CASP8	association	0.800	3
FADD	proximity	0.790	2
SNX33	physical association	0.780	2
FAS	association	0.760	6
RGS20	physical association	0.720	9
PSTPIP1	physical association	0.700	5
NCK2	physical association	0.680	4
PRMT2	association	0.640	2
SNX9	physical association	0.640	2
NCK1	physical association	0.620	7
SRGAP2	direct interaction	0.610	2
FNBP1	physical association	0.590	4
PACSIN1	physical association	0.590	4
PACSIN2	physical association	0.590	4
PACSIN3	physical association	0.590	4
TRIP10	physical association	0.590	4
FYN	direct interaction	0.570	2
PIK3R1	direct interaction	0.570	2
CYSRT1	physical association	0.560	3
ECM1	physical association	0.560	3
IHO1	physical association	0.560	3
KRT33B	physical association	0.560	3
KRT40	physical association	0.560	3
KRTAP11-1	physical association	0.560	3
KRTAP12-3	physical association	0.560	3
NOTCH2NLA	physical association	0.560	3
SEC23A	physical association	0.560	3
TNS2	physical association	0.560	3
TRIP6	physical association	0.560	3
ITK	direct interaction	0.540	3

BioGRID (144 interactions; top human partners by supporting records): FAS (Co-localization; 7 records), FADD (Co-localization; 5 records), FYN (Co-localization; 5 records), SNX33 (Affinity Capture-MS; 5 records), CASP8 (Co-purification; 4 records), EIF2AK1 (Affinity Capture-MS; 3 records), FNBP1 (Affinity Capture-MS; 3 records), GRB2 (Affinity Capture-Western; 3 records), LEPREL2 (Affinity Capture-MS; 3 records), MOSPD2 (Affinity Capture-MS; 3 records), NCK1 (Two-hybrid; 3 records), PACSIN2 (Affinity Capture-MS; 3 records), PRMT2 (Affinity Capture-MS; 3 records), SNX9 (Affinity Capture-MS; 3 records), TNFRSF6B (Affinity Capture-Western; 3 records)

SIGNOR signaling

showing 6 of 7 signaling interactions:

A	Effect	B	Mechanism
FASLG	“up-regulates activity”	FAS	binding
FOXO	“up-regulates quantity by expression”	FASLG	“transcriptional regulation”
TP53	“up-regulates quantity by expression”	FASLG	“transcriptional regulation”
FOXO3	“up-regulates quantity by expression”	FASLG	“transcriptional regulation”
TNFRSF6B	down-regulates	FASLG	binding
FOXS1	“down-regulates quantity by repression”	FASLG	“transcriptional regulation”

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
TNFRSF6B	ligand	Signaling by Tumor necrosis factor
FAS	ligand	Signaling by Tumor necrosis factor

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of signaling by CBL	6	47.3×	5e-07
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	41.2×	4e-06
Signaling by CSF1 (M-CSF) in myeloid cells	6	33.0×	2e-06
Downstream signal transduction	5	30.2×	1e-05
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	5	28.3×	1e-05
FCGR3A-mediated phagocytosis	9	26.7×	2e-08
RHOU GTPase cycle	6	26.5×	3e-06
Signaling by SCF-KIT	6	23.6×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
plasma membrane tubulation	6	88.7×	2e-08
Fc-gamma receptor signaling pathway involved in phagocytosis	5	46.2×	9e-06
negative regulation of inflammatory response to antigenic stimulus	5	39.6×	2e-05
ephrin receptor signaling pathway	8	36.2×	2e-08
extrinsic apoptotic signaling pathway via death domain receptors	6	31.7×	6e-06
peptidyl-tyrosine phosphorylation	5	27.7×	8e-05
positive regulation of actin filament polymerization	5	21.7×	2e-04
T cell receptor signaling pathway	7	14.0×	7e-05

Disease & clinical

Genetic variants

Variant evidence for FASLG: 241 ClinVar records (7 pathogenic / likely pathogenic); 24 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

241 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	109
Likely benign	86
Benign	13

Top pathogenic / likely-pathogenic (7)

Showing all 7 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1327546	NM_000639.3(FASLG):c.605G>C (p.Cys202Ser)	Pathogenic	criteria provided, single submitter	2
1428184	NM_000639.3(FASLG):c.343C>T (p.Arg115Ter)	Pathogenic	criteria provided, single submitter	1
2765866	NM_000639.3(FASLG):c.44del (p.Val15fs)	Pathogenic	criteria provided, single submitter	1
1327544	NM_000639.3(FASLG):c.829G>A (p.Gly277Ser)	Likely pathogenic	criteria provided, single submitter	2
3393343	NM_000639.3(FASLG):c.739del (p.Ala247fs)	Likely pathogenic	criteria provided, single submitter	1
3905909	NM_000639.3(FASLG):c.808G>T (p.Glu270Ter)	Likely pathogenic	criteria provided, single submitter	1
16495	NM_000639.3(FASLG):c.473_556del (p.Met158_Glu185del)	Pathogenic	no assertion criteria provided	2

Per-variant reference — Sugi Variant

Explore FASLG’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 150):

Position(s)	Effect	Δscore	Sites
1:172659550–172659551	donor_loss	0.9900	5
1:172660141–172660142	donor_loss	0.9900	5
1:172664326	acceptor_gain	0.9900
1:172660084	acceptor_gain	0.9800
1:172660093–172660094	acceptor_loss	0.9800	6
1:172664332–172664333	acceptor_loss	0.9800	6
1:172664372	donor_gain	0.9800
1:172660091	acceptor_gain	0.9700
1:172665294	donor_gain	0.9700
1:172665620–172665621	acceptor_loss	0.9700	6

AlphaMissense

318 missense substitutions predicted likely pathogenic (of 1,826 scored), across 97 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F276	8	0.938	0.978
H148	8	0.866	0.969
H209	8	0.836	0.957
W162	7	0.977	0.998
F197	7	0.947	0.977
C233	7	0.942	0.968
W239	7	0.940	0.991
C202	7	0.927	0.952
F190	7	0.914	0.980
F275	7	0.881	0.988
F249	7	0.862	0.965
M225	7	0.847	0.914
D255	7	0.801	0.891
G277	6	0.942	0.986
G187	6	0.914	0.978
G246	5	0.957	0.981
Y192	5	0.946	0.980
Y189	5	0.912	0.984
V259	5	0.880	0.988
T274	5	0.837	0.952

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	favorable	0.000712

Disease associations

OMIM: gene MIM:134638 | disease phenotypes: MIM:211980, MIM:601859

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
autoimmune lymphoproliferative syndrome type 1	Strong	Autosomal recessive	4
autoimmune lymphoproliferative syndrome	Strong	Autosomal recessive	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
autoimmune lymphoproliferative syndrome type 1	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
COVID-19 research	green
Cytopenia - NOT Fanconi anaemia	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (3): lung cancer (MONDO:0008903), autoimmune lymphoproliferative syndrome type 1 (MONDO:0011158), autoimmune lymphoproliferative syndrome (MONDO:0017979)

Orphanet (1): Autoimmune lymphoproliferative syndrome (Orphanet:3261)

HPO phenotypes

showing 60 of 85 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000083	Renal insufficiency
HP:0000099	Glomerulonephritis
HP:0000554	Uveitis
HP:0000854	Thyroid adenoma
HP:0000978	Bruising susceptibility
HP:0001025	Urticaria
HP:0001250	Seizure
HP:0001369	Arthritis
HP:0001402	Hepatocellular carcinoma
HP:0001442	Typified by somatic mosaicism
HP:0001744	Splenomegaly
HP:0001789	Hydrops fetalis
HP:0001880	Increased total eosinophil count
HP:0001888	Decreased total lymphocyte count
HP:0001890	Autoimmune hemolytic anemia
HP:0001891	Iron deficiency anemia
HP:0001892	Abnormal bleeding
HP:0001904	Autoimmune neutropenia
HP:0001923	Reticulocytosis
HP:0001971	Hypersplenism
HP:0001973	Autoimmune thrombocytopenia
HP:0002113	Pulmonary infiltrates
HP:0002206	Pulmonary fibrosis
HP:0002240	Hepatomegaly
HP:0002315	Headache
HP:0002583	Colitis
HP:0002633	Vasculitis
HP:0002671	Basal cell carcinoma
HP:0002716	Lymphadenopathy
HP:0002725	Systemic lupus erythematosus
HP:0002729	Follicular hyperplasia
HP:0002730	Chronic noninfectious lymphadenopathy
HP:0002731	Decreased T cell apoptosis
HP:0002848	Decreased specific anti-polysaccharide antibody concentration
HP:0002850	Decreased circulating IgM concentration
HP:0002851	Increased double-negative T cell number
HP:0002853	Increased HLA-DR+ CD4+ T cell proportion
HP:0002890	Thyroid carcinoma
HP:0002923	Rheumatoid factor positive
HP:0002960	Autoimmunity
HP:0002972	Reduced delayed hypersensitivity
HP:0003212	Increased circulating IgE concentration
HP:0003237	Increased circulating IgG concentration
HP:0003261	Increased circulating IgA concentration
HP:0003262	Anti-smooth muscle antibody positivity
HP:0003453	Antineutrophil antibody positivity
HP:0003454	Platelet antibody positive
HP:0003493	Antinuclear antibody positivity
HP:0003496	Increased circulating IgM concentration
HP:0003613	Antiphospholipid antibody positivity
HP:0004315	Decreased circulating IgG concentration
HP:0004341	Abnormal vitamin B12 concentration
HP:0004844	Coombs-positive hemolytic anemia
HP:0005263	Gastritis
HP:0005404	Increased total B cell count
HP:0005528	Bone marrow hypocellularity
HP:0006519	Alveolar cell carcinoma
HP:0008069	Neoplasm of the skin
HP:0008209	Premature ovarian insufficiency

GWAS associations

24 associations:

Study	Trait	p-value
GCST001729_12	Crohn’s disease	6e-22
GCST004785_10	Vitiligo	7e-17
GCST000879_37	Crohn’s disease	2e-15
GCST007800_7	Asthma (childhood onset)	6e-13
GCST010984_8	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	2e-12
GCST010985_17	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	1e-11
GCST005523_3	Celiac disease	1e-10
GCST004346_58	Psoriasis	3e-10
GCST005038_74	Allergic disease (asthma, hay fever or eczema)	3e-10
GCST006408_17	Allergic sensitization	9e-10
GCST90013445_41	Type 1 diabetes	2e-9
GCST90013445_5	Type 1 diabetes	2e-9
GCST009873_22	Autoimmune traits (pleiotropy)	4e-9
GCST005523_4	Celiac disease	8e-9
GCST008489_2	Celiac disease	3e-8
GCST004861_7	Itch intensity from mosquito bite	4e-8
GCST005752_149	Systemic lupus erythematosus	7e-8
GCST007798_23	Asthma	1e-7
GCST007800_76	Asthma (childhood onset)	1e-7
GCST002520_2	Celiac disease	8e-7
GCST000612_38	Celiac disease	2e-6
GCST007400_69	Systemic lupus erythematosus	2e-6
GCST003518_29	Daytime sleep phenotypes	3e-6
GCST007797_20	Asthma onset (childhood vs adult)	5e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0005298	allergic sensitization measurement
EFO:0004847	age at onset

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D056735	Autoimmune Lymphoproliferative Syndrome	C15.604.515.138; C16.320.089; C20.111.288; C20.683.515.124

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5714 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the FASLG protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
ASUNERCEPT	Protein	3

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs763110	cisplatin, doxorubicin	Efficacy	Allele T is associated with decreased progression-free survival when treated with cisplatin and doxorubicin in people with Osteosarcoma as compared to allele C.	PMID:25829401

CTD chemical–gene interactions

220 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects cotreatment, increases expression, increases reaction, decreases expression, increases activity (+1 more)	11
Resveratrol	increases cleavage, increases expression, decreases reaction, affects binding, increases reaction	8
Cisplatin	affects cotreatment, decreases expression, decreases reaction, increases activity, affects binding (+3 more)	6
Quercetin	increases expression, affects cotreatment, decreases reaction	5
Paclitaxel	increases expression, increases response to substance, decreases reaction, affects cotreatment	5
SB 203580	affects reaction, increases expression, affects binding, decreases reaction, increases reaction (+1 more)	4
Acetylcysteine	affects cotreatment, decreases expression, increases activity, decreases abundance, decreases reaction (+1 more)	4
Curcumin	decreases reaction, decreases expression, affects cotreatment, increases expression	4
pyrazolanthrone	affects reaction, increases expression, decreases reaction, affects cotreatment	3
Vorinostat	affects cotreatment, increases expression, decreases reaction	3
Arsenic	affects cotreatment, decreases expression, increases expression	3
Benzo(a)pyrene	decreases reaction, increases cleavage, increases reaction, affects binding, increases activity (+1 more)	3
Doxorubicin	increases response to substance, decreases reaction, increases expression, affects cotreatment	3
Nicotine	increases expression	3
Plant Extracts	increases expression, decreases expression, decreases reaction	3
Rifampin	decreases reaction, increases expression, decreases expression	3
Tamoxifen	affects cotreatment, decreases expression, decreases reaction, increases expression	3
Mitomycin	increases expression	3
bisphenol A	affects cotreatment, increases expression	2
sodium arsenite	increases localization, increases stability, affects activity, affects cotreatment, increases cleavage	2
dioscin	increases expression	2
bufalin	increases expression	2
casticin	decreases expression, increases expression	2
usnic acid	affects cotreatment, decreases expression, increases expression	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	2
3,5-bis(2-fluorobenzylidene)piperidin-4-one	decreases reaction, increases expression	2
(+)-JQ1 compound	affects cotreatment, increases expression, decreases expression	2
Bortezomib	affects cotreatment, increases expression, increases activity, increases reaction, decreases reaction	2
Fulvestrant	decreases expression, decreases methylation, increases expression	2
Dexamethasone	decreases expression, decreases secretion	2

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000318	Binding	Inhibition of Fas ligand-mediated death of human Jurkat T cells upto 20 uM after 30 mins by 51Cr release assay	Dihydrofuro[3,4-c]pyridinones as inhibitors of the cytolytic effects of the pore-forming glycoprotein perforin. — *J Med Chem*

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E4AB	L5178Y/hFASL	Cancer cell line	Female
CVCL_SN14	HAP1 FASLG (-) 1	Cancer cell line	Male
CVCL_SN15	HAP1 FASLG (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00158041	Phase 4	COMPLETED	Subcutaneous Amifostine Safety Study
NCT00277160	Phase 4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00365508	Phase 4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00440960	Phase 4	COMPLETED	Anesthesia in Flexible Bronchoscopy for Lung Cancer Diagnostic
NCT00492843	Phase 4	TERMINATED	Loading Dose or Standard Dose of Intravenous Ibandronate in Treating Patients With Lung Cancer and Skeletal Metastasis
NCT00666978	Phase 4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00675168	Phase 4	UNKNOWN	Positron Emission Tomography (PET)/Computed Tomography (CT) and Roentgen in Lung Cancer: Evaluation of Patients in General Practice
NCT00712647	Phase 4	COMPLETED	Carotene and Retinol Efficacy Trial
NCT00747773	Phase 4	COMPLETED	Cryospray Ablation of Surgical Resection Specimens To Determine Safety And Histological Effect In The Lung
NCT01060137	Phase 4	COMPLETED	Fentanyl Matrix in Lung Cancer Pain
NCT01381627	Phase 4	UNKNOWN	Safety Evaluation of Dexmedetomidine for EBUS-TBNA
NCT01741506	Phase 4	COMPLETED	Coagulation Profile in Patients Undergoing Video Assisted Thorascopic Surgery (VATS) for Lung Cancer
NCT02246023	Phase 4	COMPLETED	Fractionated Versus Target-controlled Propofol Administration in Bronchoscopy
NCT02275702	Phase 4	COMPLETED	Randomized Study of Preoperative Dexamethasone for Quality of Recovery in VATS Lung Resection Patients
NCT02346318	Phase 4	UNKNOWN	The Randomized Controlled Clinical Trial of Kushen Injection
NCT02476526	Phase 4	COMPLETED	Safety of Low Dose IV Contrast CT Scanning in Chronic Kidney Disease
NCT02490059	Phase 4	COMPLETED	Ultrathin Bronchoscopy for Solitary Pulmonary Nodules
NCT02504801	Phase 4	UNKNOWN	Efficacy of Nebulized Pulmicort Respules in Primary Lung Cancer Patients With COPD
NCT02869789	Phase 4	COMPLETED	An Investigational Immuno-therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers
NCT03302221	Phase 4	WITHDRAWN	Regional Haemodynamic Changes in Radial Artery Assessment With Continuous Pulsed-wave Doppler Ultrasound
NCT03313544	Phase 4	UNKNOWN	Evolution of the Heart Function When Monitoring Immunotherapies Anti-cancerous Inhibiting PD-1
NCT03394222	Phase 4	COMPLETED	Effect of Preoperative Budesonide Inhalation on Arterial Blood Oxygenation and Intrapulmonary Shunt During OLV
NCT03570645	Phase 4	COMPLETED	Comparison of the Duration of Ropivacaine Combined With Dexmedetomidine or Dexamethasone on Paravertebral Block
NCT03571126	Phase 4	UNKNOWN	Olanzapine for the Prevention and Treatment of Nausea and Vomiting Induced by Chemotherapy of Lung Cancer
NCT03642457	Phase 4	TERMINATED	Efficacy Between Serratus Plane Block And Local Infiltration In Vats
NCT04145570	Phase 4	COMPLETED	A Single-Dose,ComparativeBioavailability Study ofTwo Formulations ofErlotinib150mgTabletsunderFastingConditions
NCT04155008	Phase 4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04613284	Phase 4	UNKNOWN	Rh-Endostatin Combined With CCRT(50 Gy) Followed by Durvalumab Maintenance for the Treatment of Specific Phase III NSCLC
NCT05463913	Phase 4	RECRUITING	Lung Nodule Detection Using Ultra-long FOV PET/CT
NCT05521789	Phase 4	RECRUITING	Erector Spinae Block for Thoracic Surgery
NCT05525338	Phase 4	RECRUITING	Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels
NCT05663242	Phase 4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Lung Tumors and Its Mechanism of Action
NCT05926336	Phase 4	UNKNOWN	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06105801	Phase 4	RECRUITING	EBUS-TBNA vs Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing
NCT06276933	Phase 4	NOT_YET_RECRUITING	A Study of Camrelizumab Combined With Chemotherapy ± Thalidomide in First-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
NCT06646471	Phase 4	RECRUITING	PROspective Master-protocol for Evaluation of Systemic THErapeutics in Elderly With Thoracic Malignancies
NCT07405086	Phase 4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT07743333	Phase 4	COMPLETED	Nebulized Lidocaine And Ketamine Before Fiberoptic Bronchoscopy
NCT07761351	Phase 4	RECRUITING	A Randomized Controlled Trial Comparing Percutaneous CT-Guided Biopsy and Shape-Sensing Robotic-Assisted Bronchoscopy
NCT07802847	Phase 4	NOT_YET_RECRUITING	Innovative and Cooperative Pathway Integrating Oncogeriatric, Pharmaceutical and Pharmacological Follow-up in Elderly Patients.
NCT00002550	Phase 3	COMPLETED	Chemotherapy Plus Radiation Therapy With or Without Surgery in Treating Patients With Stage IIIA Non-small Cell Lung Cancer
NCT00002583	Phase 3	COMPLETED	Vinorelbine + Cisplatin or No Further Therapy in Non-small Cell Lung Cancer That Has Been Surgically Removed
NCT00002623	Phase 3	COMPLETED	Chemotherapy Followed by Surgery or Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer
NCT00002822	Phase 3	COMPLETED	Combination Chemotherapy Followed by Radiation Therapy in Patients With Small Cell Lung Cancer
NCT00002823	Phase 3	COMPLETED	Combination Chemotherapy Compared With No Treatment Following Surgery in Treating Patients With Non-small Cell Lung Cancer
NCT00002858	Phase 3	UNKNOWN	Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Small Cell Lung Cancer
NCT00002911	Phase 3	COMPLETED	Marimastat in Treating Patients With Stage III Non-small Cell Lung Cancer
NCT00003011	Phase 3	COMPLETED	Marimastat Following Chemotherapy in Treating Patients With Small Cell Lung Cancer
NCT00003053	Phase 3	UNKNOWN	Combination Chemotherapy in Treating Patients With Stage I, II, or IIIA Non-small Cell Lung Cancer That Has Been Surgically Removed
NCT00003117	Phase 3	COMPLETED	Paclitaxel With or Without Carboplatin in Treating Patients With Advanced Non-small Cell Lung Cancer
NCT00003159	Phase 3	COMPLETED	Surgery With or Without Preoperative Chemotherapy in Treating Patients With Resectable Non-small Cell Lung Cancer
NCT00003235	Phase 3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer That Can Not Be Surgically Removed
NCT00003240	Phase 3	UNKNOWN	Standard Therapy Given With or Without Combination Chemotherapy in Treating Patients With Non-small Cell Lung Cancer
NCT00003279	Phase 3	COMPLETED	Vaccination Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer
NCT00003299	Phase 3	COMPLETED	Cisplatin Plus Etoposide With or Without Paclitaxel in Treating Patients With Extensive-Stage Small Cell Lung Cancer
NCT00003313	Phase 3	COMPLETED	Amifostine in Treating Patients With Stage II or Stage III Non-small Cell Lung Cancer
NCT00003317	Phase 3	COMPLETED	Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Stage IIIA Non-small Cell Lung Cancer
NCT00003364	Phase 3	COMPLETED	Radiation Therapy Plus Combination Chemotherapy In Treating Patients With Limited Stage Small Cell Lung Cancer
NCT00003387	Phase 3	COMPLETED	Carboplatin, Paclitaxel, and Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed During Surgery
NCT00003447	Phase 3	UNKNOWN	Vinorelbine and/or Gemcitabine in Treating Older Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer