FAS

Summary

FAS (Fas cell surface death receptor, HGNC:11920) is a protein-coding gene on chromosome 10q23.31, encoding Tumor necrosis factor receptor superfamily member 6 (P25445). Receptor for TNFSF6/FASLG.

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.

Source: NCBI Gene 355 — RefSeq curated summary.

At a glance

• Gene–disease (curated): FAS-related autoimmune lymphoproliferative immune disorder (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 504 total — 73 pathogenic, 37 likely-pathogenic
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• MANE Select transcript: NM_000043

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11920
Approved symbol	FAS
Name	Fas cell surface death receptor
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	CD95, APO-1
Ensembl gene	ENSG00000026103
Ensembl biotype	protein_coding
OMIM	134637
Entrez	355

Gene structure

Transcript identifiers

Ensembl transcripts: 61 — 22 retained_intron, 19 protein_coding, 11 protein_coding_CDS_not_defined, 9 nonsense_mediated_decay

ENST00000313771, ENST00000355279, ENST00000355740, ENST00000357339, ENST00000371857, ENST00000460510, ENST00000466081, ENST00000477270, ENST00000479522, ENST00000484444, ENST00000487314, ENST00000488877, ENST00000492756, ENST00000494410, ENST00000494799, ENST00000562983, ENST00000612663, ENST00000640140, ENST00000640250, ENST00000640681, ENST00000652046, ENST00000688239, ENST00000690268, ENST00000696723, ENST00000696741, ENST00000696742, ENST00000696743, ENST00000696744, ENST00000696767, ENST00000696768, ENST00000696769, ENST00000696770, ENST00000696771, ENST00000696772, ENST00000696773, ENST00000696774, ENST00000696775, ENST00000696776, ENST00000696777, ENST00000696778, ENST00000696779, ENST00000696780, ENST00000696781, ENST00000696782, ENST00000696783, ENST00000696992, ENST00000696993, ENST00000696994, ENST00000696995, ENST00000696996, ENST00000696997, ENST00000696998, ENST00000696999, ENST00000697035, ENST00000697036, ENST00000697037, ENST00000697093, ENST00000697094, ENST00000697095, ENST00000697096, ENST00000697097

RefSeq mRNA: 5 — MANE Select: NM_000043 NM_000043, NM_001320619, NM_001410956, NM_152871, NM_152872

CCDS: CCDS7393, CCDS7394, CCDS7395, CCDS91296, CCDS91297

Canonical transcript exons

ENST00000652046 — 9 exons

Exon	Start	End
ENSE00003465967	89007700	89007837
ENSE00003500194	89010753	89010815
ENSE00003513797	89013343	89013367
ENSE00003579795	89008889	89008997
ENSE00003586177	89010539	89010600
ENSE00003666791	89003029	89003194
ENSE00003673777	89011999	89012081
ENSE00003969232	89014119	89017059
ENSE00003969492	88990798	88990906

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 95.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.7395 / max 477.4839, expressed in 1670 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106093	13.6601	1620
106091	4.7961	1141
106094	1.6816	655
106092	1.0299	368
106087	0.6574	286
106090	0.4604	252
106089	0.4085	241
106086	0.0269	4
106088	0.0186	3

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	95.49	gold quality
left ovary	UBERON:0002119	94.94	gold quality
right ovary	UBERON:0002118	94.45	gold quality
gall bladder	UBERON:0002110	93.94	gold quality
epithelium of nasopharynx	UBERON:0001951	93.90	gold quality
nasopharynx	UBERON:0001728	93.88	gold quality
right lung	UBERON:0002167	93.70	gold quality
left adrenal gland	UBERON:0001234	93.67	gold quality
stromal cell of endometrium	CL:0002255	93.46	gold quality
right adrenal gland cortex	UBERON:0035827	93.19	gold quality
left adrenal gland cortex	UBERON:0035825	93.13	gold quality
right adrenal gland	UBERON:0001233	92.99	gold quality
upper lobe of left lung	UBERON:0008952	92.85	gold quality
right uterine tube	UBERON:0001302	92.83	gold quality
upper lobe of lung	UBERON:0008948	92.57	gold quality
calcaneal tendon	UBERON:0003701	92.54	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.38	gold quality
monocyte	CL:0000576	92.12	gold quality
mononuclear cell	CL:0000842	92.03	gold quality
leukocyte	CL:0000738	91.92	gold quality
left uterine tube	UBERON:0001303	91.83	gold quality
adrenal cortex	UBERON:0001235	91.82	gold quality
colonic mucosa	UBERON:0000317	91.64	gold quality
vermiform appendix	UBERON:0001154	91.57	gold quality
germinal epithelium of ovary	UBERON:0001304	91.50	gold quality
adrenal gland	UBERON:0002369	91.50	gold quality
body of uterus	UBERON:0009853	91.24	gold quality
left coronary artery	UBERON:0001626	91.23	gold quality
superficial temporal artery	UBERON:0001614	91.21	gold quality
ovary	UBERON:0000992	91.05	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	12.58
E-CURD-89	no	850.72
E-CURD-120	no	30.64
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF2, ATM, BHLHE40, CEBPA, CEBPB, CEBPG, CEBPZ, CNBP, DDIT3, DNMT1, EGR1, ESR1, ETS1, FOS, GLI1, GLI2, HDGF, HSF1, ID2, ID3, IRF8, JUN, MLXIPL, MYC, NFKB1, NFKB2, NFKB, NFKBIA, NFYA, NFYB, NFYC, NR3C1, PPARG, PURA, RELA, SMAD5, SP1, SP3, SREBF1

miRNA regulators (miRDB)

116 targeting FAS, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-LET-7A-2-3P	99.87	70.53	1921

Literature-anchored findings (GeneRIF, showing 40)

• A significant correlation with differentiation status of the tumor was found for the p53 aberration but not for CD95 expression. (PMID:11692157)
• Regulation of Fas expression by STAT3 and c-Jun is mediated by phosphatidylinositol 3-kinase-AKT signaling (PMID:11733515)
• its polymorphism may contributes to the pathogenesis of spondyloarthropathy (PMID:11771526)
• induction of gene expression by doxorubicin in endothelial cells through a p53-dependent mechanism (PMID:11779855)
• Soluble Fas antigen (sFAS) in the serum from patients with adrenal tumors. (PMID:11782802)
• Butyrate induced apoptosis via the Fas/Fas L system and potentiated Fas-triggered apoptosis in MCF-7 cells. (PMID:11786482)
• Expression of Fas and Fas ligand in esophageal tissue mucosa and carcinomas (PMID:11788891)
• Cytochrome c release upon Fas receptor activation (PMID:11790791)
• expression was significantly increased in neonates with pontosubicular neuron necrosis (PMID:11809905)
• FAS germline mutations have been associated with the development of autoimmune lymphoproliferative syndrome (ALPS). (PMID:11830507)
• Participation of Fas-mediated apoptotic pathway in KB, a human head and neck squamous cell carcinoma cell line, after irradiation (PMID:11836578)
• expression associated with apoptosis in sun-exposed keratinocytes (PMID:11857317)
• myelodysplastic syndrome CD34(+)-derived erythroid progenitors underwent abnormal Fas-dependent apoptosis during differentiation that could be responsible for the impaired erythropoiesis. (PMID:11861273)
• Met sequesters Fas, preventing apoptosis. (PMID:11864613)
• Overexpression of the mouse Fas gene in human Hep3B hepatoma cells overcomes their resistance to Fas-mediated apoptosis. (PMID:11867183)
• Plasma FasL levels were significantly high in patients with grade II - IV graft-versus-host disease. (PMID:11877055)
• Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia (PMID:11891278)
• 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)
• Decreased function of Fas in patients displaying delayed progression of HIV-induced immune deficiency (PMID:11920253)
• Mature dendritic cells are protected from Fas/CD95-mediated apoptosis by upregulation of Bcl-X(L). (PMID:11941452)
• Fas engagement increases expression of interleukin-6 in human glioma cells. (PMID:11949822)
• Differential expressions of Fas and Fas ligand in human placenta (PMID:11961305)
• Genetic polymorphisms of Fas (CD95) in human longevity (PMID:11965496)
• HLA class II signals sensitize B lymphocytes to apoptosis via CD95 (PMID:11975981)
• Endotoxin-induced lymphopenia was constituted by cells with the highest rates of disappearance were characterized by an activated phenotype (CD45RA(-) CD45RO(+)) as well as a phenotype linked to apoptosis (CD95(+) CD28(-)) (PMID:11986289)
• Our results indicate that Fas-mediated apoptosis is important for endometrial cycling and suggest that dysregulation of the Fas/FasL interactions may have an important role in the development of endometrial cancer. (PMID:11994542)
• “trophoblast-cytokine-Fas/FasL triad” determines the ability of the Fas/FasL system to regulate trophoblast viability (PMID:12021072)
• data suggest that disruption of the cytoskeleton causes apoptosis via activation of CD95 and enhances UV-induced apoptosis, possibly via aiding receptor clustering (PMID:12032668)
• Recipient gene polymorphism and acute renal allograft rejection (PMID:12034188)
• alteration associated with nodal metastasis in non-small cell lung cancer (PMID:12037669)
• Data indicate that the apoptosis program in T cells includes the shedding/secretion of different forms of Fas to spread a death signal. (PMID:12049185)
• Fas defects may play a role in the pathogenesis of mycosis fungoides (PMID:12060388)
• FLIP switches Fas-mediated glucose signaling in human pancreatic beta cells from apoptosis to cell replication. (PMID:12060768)
• Fas promoter -670A/G polymorphism was significantly associated with systemic lupus erythematosus (SLE), suggesting a possibility that Fas promoter contributes, at least in part, to the pathogenesis of SLE (PMID:12064832)
• These results suggest that Fas is involved in neuronal apoptosis in the developing human brain. (PMID:12067476)
• Frequent mutations of Fas gene in nasal NK/T cell lymphoma (PMID:12096347)
• Interferon-gamma increases its expression in B-leukemia cells. (PMID:12096925)
• the death effector domain of FADD is involved in interaction with Fas. (PMID:12107169)
• CCR5 mediates Fas- and caspase-8 dependent apoptosis of both uninfected and HIV infected primary human CD4 T cells (PMID:12131184)
• the role of Fas/Fas ligand (FasL) in tum orgenesis, immune escape, counterattack in colonic cancer (PMID:12137598)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fas	ENSMUSG00000024778
rattus_norvegicus	Fas	ENSRNOG00000019142

Paralogs (21): TNFRSF1B (ENSG00000028137), TNFRSF9 (ENSG00000049249), RELT (ENSG00000054967), NGFR (ENSG00000064300), TNFRSF1A (ENSG00000067182), CD40 (ENSG00000101017), TNFRSF10A (ENSG00000104689), LTBR (ENSG00000111321), TNFRSF10B (ENSG00000120889), TNFRSF8 (ENSG00000120949), CD27 (ENSG00000139193), TNFRSF11A (ENSG00000141655), TNFRSF21 (ENSG00000146072), TNFRSF14 (ENSG00000157873), TNFRSF11B (ENSG00000164761), TNFRSF10D (ENSG00000173530), TNFRSF10C (ENSG00000173535), TNFRSF4 (ENSG00000186827), TNFRSF18 (ENSG00000186891), TNFRSF25 (ENSG00000215788), TNFRSF6B (ENSG00000243509)

Protein

Protein identifiers

Tumor necrosis factor receptor superfamily member 6 — P25445 (reviewed: P25445)

Alternative names: Apo-1 antigen, Apoptosis-mediating surface antigen FAS, FASLG receptor

All UniProt accessions (15): P25445, A0A087WTM9, A0A8Q3SIR6, A0A8Q3SIY4, A0A8Q3SJI5, A0A8Q3WLI5, A0A8Q3WLK1, A0A8Q3WLK6, A0A8Q3WLL4, A0A8Q3WM13, A0A8V8TKJ0, A0A8V8TKN4, A0A8V8TM64, K9J972, Q59FU8

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase CASP8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs CASP8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro).

Subunit / interactions. Component of the death-induced signaling complex (DISC) composed of cell surface receptor FAS/CD95, adapter protein FADD and the CASP8 protease; recruitment of CASP8 to the complex is required for processing of CASP8 into the p18 and p10 subunits. Interacts directly (via DED domain) with NOL3 (via CARD domain); inhibits death-inducing signaling complex (DISC) assembly by inhibiting the increase in FAS-FADD binding induced by FAS activation. Binds DAXX. Interacts with HIPK3. Part of a complex containing HIPK3 and FADD. Binds RIPK1 and FAIM2. Interacts with BABAM2 and FEM1B. Interacts with CALM. In the absence of stimulation, interacts with BIRC2, DDX3X and GSK3B. The interaction with BIRC2 and DDX3X is further enhanced upon receptor stimulation and accompanied by DDX3X and BIRC2 cleavage.

Subcellular location. Cell membrane. Membrane raft Secreted Secreted Secreted Secreted Secreted.

Tissue specificity. Isoform 1 and isoform 6 are expressed at equal levels in resting peripheral blood mononuclear cells. After activation there is an increase in isoform 1 and decrease in the levels of isoform 6.

Post-translational modifications. (Microbial infection) Glycosylated at Arg-250 by enteropathogenic E.coli protein NleB1: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions. Palmitoylated. Palmitoylation by ZDHHC7 prevents the lysosomal degradation of FAS regulating its expression at the plasma membrane. N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.

Disease relevance. Autoimmune lymphoproliferative syndrome 1A (ALPS1A) [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.

Domain organisation. Contains a death domain involved in the binding of FADD, and maybe to other cytosolic adapter proteins.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Dominant negative isoform, resistant to Fas-mediated apoptosis.

Isoforms (7)

UniProt ID	Names	Canonical?
P25445-1	1	yes
P25445-2	2, del2, D
P25445-3	3, del3, E
P25445-4	4, B
P25445-5	5, C
P25445-6	6, TMdel, A
P25445-7	7, FasExo8Del

RefSeq proteins (5): NP_000034, NP_001307548, NP_001397885, NP_690610, NP_690611 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000488	Death_dom	Domain
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR008063	Fas_rcpt	Family
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR033998	TNFRSF6_death	Domain
IPR033999	TNFRSF6_N	Domain

Pfam: PF00020, PF00531

UniProt features (100 total): sequence variant 36, splice variant 11, disulfide bond 8, mutagenesis site 8, helix 8, strand 6, glycosylation site 4, modified residue 3, repeat 3, region of interest 2, topological domain 2, sequence conflict 2, turn 2, signal peptide 1, chain 1, lipid moiety-binding region 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
3TJE	X-RAY DIFFRACTION	1.93
3THM	X-RAY DIFFRACTION	2.1
3EWT	X-RAY DIFFRACTION	2.4
3EZQ	X-RAY DIFFRACTION	2.73
9NCQ	ELECTRON MICROSCOPY	3.51
1DDF	SOLUTION NMR
2NA7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25445-F1	78.21	0.40

Antibody-complex structures (SAbDab): 2 — 3THM, 3TJE

Functional residue map

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

Post-translational modifications (4): 209, 214, 225, 199

Disulfide bonds (8): 59–73, 63–82, 85–101, 104–119, 107–127, 129–143, 146–157, 149–165

Glycosylation sites (4): 28, 118, 136, 250

Mutagenesis-validated functional residues (8):

Position	Phenotype
199	loss of palmitoylation.
250	abolished glcnacylation by e.coli nleb1.
250	strongly decreased interaction with fadd.
261	loss of interaction with fadd.
283	loss of interaction with fadd.
287	strongly decreased interaction with fadd.
291	decreased interaction with fadd.
313	constitutive activation. promotes apoptosis, both in the presence and in the absence of stimulation by a ligand.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-140534	Caspase activation via Death Receptors in the presence of ligand
R-HSA-3371378	Regulation by c-FLIP
R-HSA-5213460	RIPK1-mediated regulated necrosis
R-HSA-5218900	CASP8 activity is inhibited
R-HSA-6803211	TP53 Regulates Transcription of Death Receptors and Ligands
R-HSA-69416	Dimerization of procaspase-8
R-HSA-75157	FasL/ CD95L signaling

MSigDB gene sets: 887 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS, MODULE_64, GOBP_T_CELL_HOMEOSTASIS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, CHUANG_OXIDATIVE_STRESS_RESPONSE_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_LYMPHOCYTE_HOMEOSTASIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, HALMOS_CEBPA_TARGETS_UP

GO Biological Process (20): apoptotic process (GO:0006915), activation-induced cell death of T cells (GO:0006924), immune response (GO:0006955), signal transduction (GO:0007165), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), regulation of stress-activated MAPK cascade (GO:0032872), cellular response to amino acid starvation (GO:0034198), Fas signaling pathway (GO:0036337), regulation of apoptotic process (GO:0042981), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), protein-containing complex assembly (GO:0065003), cellular response to mechanical stimulus (GO:0071260), cellular response to hyperoxia (GO:0071455), motor neuron apoptotic process (GO:0097049), extrinsic apoptotic signaling pathway (GO:0097191), necroptotic signaling pathway (GO:0097527), positive regulation of reactive oxygen species biosynthetic process (GO:1903428), positive regulation of apoptotic signaling pathway (GO:2001235), tumor necrosis factor-mediated signaling pathway (GO:0033209)

GO Molecular Function (7): tumor necrosis factor receptor activity (GO:0005031), calmodulin binding (GO:0005516), kinase binding (GO:0019900), signaling receptor activity (GO:0038023), identical protein binding (GO:0042802), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (11): cytosol (GO:0005829), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), nuclear body (GO:0016604), death-inducing signaling complex (GO:0031264), CD95 death-inducing signaling complex (GO:0031265), membrane raft (GO:0045121), extracellular exosome (GO:0070062), extracellular region (GO:0005576), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Caspase activation via Death Receptors in the presence of ligand	2
Caspase activation via extrinsic apoptotic signalling pathway	1
Regulated Necrosis	1
Regulation of necroptotic cell death	1
TP53 Regulates Transcription of Cell Death Genes	1
Death Receptor Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
apoptotic signaling pathway	3
apoptotic process	3
cell surface receptor signaling pathway	2
regulation of apoptotic process	2
protein binding	2
programmed cell death	1
execution phase of apoptosis	1
T cell homeostasis	1
T cell apoptotic process	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
extrinsic apoptotic signaling pathway	1
regulation of MAPK cascade	1
stress-activated MAPK cascade	1
regulation of stress-activated protein kinase signaling cascade	1
cellular response to starvation	1
response to amino acid starvation	1
regulation of programmed cell death	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
cellular component assembly	1
protein-containing complex organization	1
response to mechanical stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
cellular response to increased oxygen levels	1
response to hyperoxia	1
cellular response to chemical stress	1
neuron apoptotic process	1
signal transduction	1
necroptotic process	1
positive regulation of biosynthetic process	1
reactive oxygen species biosynthetic process	1
regulation of reactive oxygen species biosynthetic process	1

Protein interactions and networks

STRING

2638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAS	FASLG	P48023	999
FAS	FADD	Q13158	998
FAS	CASP8	Q14790	998
FAS	TNF	P01375	997
FAS	TNFRSF1A	P19438	994
FAS	TNFSF10	P50591	993
FAS	DAXX	Q9UER7	941
FAS	TNFRSF10A	O00220	931
FAS	PTPN13	Q12923	923
FAS	TNFRSF10B	O14763	917
FAS	TRADD	Q15628	901
FAS	CFLAR	O15519	867
FAS	CASP3	P42574	851
FAS	CD40	P25942	850
FAS	RIPK1	Q13546	842

IntAct

159 interactions, top by confidence:

A	B	Type	Score
FAS	FADD	psi-mi:“MI:0915”(physical association)	0.960
FADD	FAS	psi-mi:“MI:0915”(physical association)	0.960
FAS	FADD	psi-mi:“MI:0914”(association)	0.960
FAS	FADD	psi-mi:“MI:2364”(proximity)	0.960
FAS	FADD	psi-mi:“MI:0407”(direct interaction)	0.960
FAS	FADD	psi-mi:“MI:0403”(colocalization)	0.960
CASP8	FAS	psi-mi:“MI:0915”(physical association)	0.920
FAS	CASP8	psi-mi:“MI:0915”(physical association)	0.920
CASP8	FAS	psi-mi:“MI:0403”(colocalization)	0.920
FAS	CASP8	psi-mi:“MI:0403”(colocalization)	0.920
FASLG	FAS	psi-mi:“MI:0914”(association)	0.760
FASLG	FAS	psi-mi:“MI:0915”(physical association)	0.760
FAS	FASLG	psi-mi:“MI:0407”(direct interaction)	0.760

BioGRID (517): FAS (Affinity Capture-MS), TUBB4A (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB2A (Affinity Capture-MS), TUBB2B (Affinity Capture-MS), COX16 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), ALDH1L2 (Affinity Capture-MS), EHD1 (Affinity Capture-MS), RUFY1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), SPATA5 (Affinity Capture-MS), MAP1S (Affinity Capture-MS), GPD1L (Affinity Capture-MS), ECSIT (Affinity Capture-MS)

ESM2 similar proteins: A5D7R1, D3ZF92, F1LW30, O00300, O08712, O08727, O14763, O62802, O70458, O70535, O75509, O77736, O95256, P01590, P20334, P20352, P22934, P25118, P25445, P25446, P26897, P30836, P41690, P42703, P51867, P83626, Q07011, Q13478, Q5M9I1, Q61098, Q63199, Q65Z14, Q6UXZ4, Q6X782, Q6X784, Q6X786, Q764M8, Q8K1S2, Q8K5B1, Q90VY2

Diamond homologs: O14798, O77736, P25445, P25446, P47741, P51867, Q3ZTK5, Q63199, Q80WM9, Q8SQ34, Q92956, Q9BDN0, Q9BDN4, Q9BDP2, Q9TSN4, Q9QZM4, O00220, O14763, O35714, P15725, P43489, Q9Y5U5, Q9Y6Q6, A5D7R1, P25942, P26842, Q3LRP1, F5HAM0, P07174, P08138, P18519, P36941, Q68396, Q7YRL5, Q9UBN6, Q9Z0W1

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
FAS	up-regulates	MAP3K5	binding
AKT	down-regulates	FAS
FAS	“up-regulates activity”	FADD	binding
RIPK1	“up-regulates activity”	FAS	binding
FAS	up-regulates	RASSF1
FASLG	“up-regulates activity”	FAS	binding
FAS	“up-regulates activity”	FAS	binding
AKT1	down-regulates	FAS
EGR1	“down-regulates quantity by repression”	FAS	“transcriptional regulation”
DAXX	down-regulates	FAS	binding
FAS	up-regulates	DAXX
TP53	“up-regulates quantity by expression”	FAS	“transcriptional regulation”
FAS	“up-regulates activity”	RIPK1	binding
MLXIPL	“up-regulates quantity by expression”	FAS	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 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
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	5	28.0×	4e-05
Transport of connexons to the plasma membrane	5	28.0×	4e-05
Formation of tubulin folding intermediates by CCT/TriC	6	26.2×	1e-05
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	6	25.2×	1e-05
RHO GTPases activate IQGAPs	7	25.0×	4e-06
Gap junction trafficking and regulation	5	24.5×	6e-05
Gap junction trafficking	5	24.5×	6e-05
Post-chaperonin tubulin folding pathway	5	24.5×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	5	31.1×	2e-04
positive regulation of extrinsic apoptotic signaling pathway	6	24.2×	1e-04
extrinsic apoptotic signaling pathway via death domain receptors	6	21.3×	2e-04
T cell costimulation	5	16.6×	2e-03
extrinsic apoptotic signaling pathway	6	16.3×	4e-04
apoptotic signaling pathway	8	15.9×	5e-05
positive regulation of neuron apoptotic process	5	12.0×	5e-03
positive regulation of apoptotic process	12	6.0×	2e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — CESC, DLBCLNOS, MLYM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	73
Likely pathogenic	37
Uncertain significance	219
Likely benign	99
Benign	36

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1067934	NM_000043.6(FAS):c.778G>A (p.Asp260Asn)	Pathogenic
1070181	NM_000043.6(FAS):c.676+1G>T	Pathogenic
1070958	NM_000043.6(FAS):c.442A>T (p.Lys148Ter)	Pathogenic
1071139	NM_000043.6(FAS):c.644T>A (p.Leu215Ter)	Pathogenic
1074734	NM_000043.6(FAS):c.657del (p.Val220fs)	Pathogenic
1357498	NM_000043.6(FAS):c.816del (p.Glu272fs)	Pathogenic
1373595	NM_000043.6(FAS):c.707_708insG (p.Ile236fs)	Pathogenic
1413808	NM_000043.6(FAS):c.182_183insTTAT (p.Lys61fs)	Pathogenic
1443489	NM_000043.6(FAS):c.312dup (p.Arg105Ter)	Pathogenic
1451181	NM_000043.6(FAS):c.259G>T (p.Glu87Ter)	Pathogenic
1455090	NM_000043.6(FAS):c.403del (p.Cys135fs)	Pathogenic
1457614	NM_000043.6(FAS):c.528G>A (p.Trp176Ter)	Pathogenic
1506283	NM_000043.6(FAS):c.506-16A>G	Pathogenic
16497	NM_000043.6(FAS):c.232del (p.Asp78fs)	Pathogenic
16498	NM_000043.6(FAS):c.334+2dup	Pathogenic
16499	NM_000043.6(FAS):c.721A>C (p.Thr241Pro)	Pathogenic
16500	NM_000043.6(FAS):c.569-2A>C	Pathogenic
16501	NM_000043.6(FAS):c.817C>T (p.Gln273Ter)	Pathogenic
16504	NM_000043.6(FAS):c.779A>T (p.Asp260Val)	Pathogenic
16505	NM_000043.6(FAS):c.749G>C (p.Arg250Pro)	Pathogenic
16507	NM_000043.6(FAS):c.651+2T>A	Pathogenic
16508	NM_000043.6(FAS):c.73G>A (p.Ala25Thr)	Pathogenic
16509	NM_000043.6(FAS):c.968_987dup (p.Glu330fs)	Pathogenic
16510	NM_000043.6(FAS):c.763A>G (p.Asn255Asp)	Pathogenic
16511	NM_000043.6(FAS):c.353A>G (p.Asn118Ser)	Pathogenic
16512	NM_000043.6(FAS):c.532T>C (p.Cys178Arg)	Pathogenic
16513	NM_000043.6(FAS):c.740G>C (p.Gly247Ala)	Pathogenic
16514	NM_000043.6(FAS):c.651+2T>C	Pathogenic
16515	NM_000043.6(FAS):c.692_693insT (p.Lys231fs)	Pathogenic
16516	NM_000043.6(FAS):c.778G>T (p.Asp260Tyr)	Pathogenic

SpliceAI

1499 predictions. Top by Δscore:

Variant	Effect	Δscore
10:89003024:TACA:T	acceptor_loss	1.0000
10:89003027:A:AC	acceptor_loss	1.0000
10:89003190:TCCAG:T	donor_loss	1.0000
10:89003191:CCAG:C	donor_loss	1.0000
10:89003192:CAG:C	donor_loss	1.0000
10:89003193:AGGTA:A	donor_loss	1.0000
10:89003195:G:T	donor_loss	1.0000
10:89003196:T:G	donor_loss	1.0000
10:89010537:A:AG	acceptor_gain	1.0000
10:89010537:AGA:A	acceptor_loss	1.0000
10:89010537:AGAT:A	acceptor_gain	1.0000
10:89010538:G:GA	acceptor_gain	1.0000
10:89010538:GA:G	acceptor_gain	1.0000
10:89010538:GAT:G	acceptor_gain	1.0000
10:89010538:GATG:G	acceptor_gain	1.0000
10:89010538:GATGT:G	acceptor_gain	1.0000
10:89010596:GGAAG:G	donor_gain	1.0000
10:89010597:GAAG:G	donor_gain	1.0000
10:89010597:GAAGG:G	donor_gain	1.0000
10:89010598:A:T	donor_gain	1.0000
10:89010599:AGG:A	donor_loss	1.0000
10:89010601:G:C	donor_loss	1.0000
10:89010602:T:A	donor_loss	1.0000
10:89011631:T:A	acceptor_gain	1.0000
10:89011632:G:A	acceptor_gain	1.0000
10:89011671:C:CA	acceptor_gain	1.0000
10:89014113:TTTCA:T	acceptor_loss	1.0000
10:89014114:TTCA:T	acceptor_loss	1.0000
10:89014115:TCAG:T	acceptor_loss	1.0000
10:89014116:CAGAT:C	acceptor_loss	1.0000

AlphaMissense

2224 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:89014191:G:C	R250P	0.986
10:89014272:T:C	L277P	0.985
10:89014283:T:A	W281R	0.985
10:89014283:T:C	W281R	0.985
10:89014285:G:C	W281C	0.985
10:89014285:G:T	W281C	0.985
10:89014188:T:A	V249D	0.982
10:89014278:G:C	R279P	0.980
10:89008939:T:A	C129S	0.974
10:89008940:G:C	C129S	0.974
10:89008933:T:A	C127S	0.973
10:89008934:G:C	C127S	0.973
10:89008954:T:C	F134L	0.973
10:89008956:T:A	F134L	0.973
10:89008956:T:G	F134L	0.973
10:89014185:T:C	F248S	0.973
10:89008909:T:A	C119S	0.972
10:89008910:G:C	C119S	0.972
10:89003194:G:T	G66C	0.971
10:89007822:T:A	C107S	0.971
10:89007823:G:C	C107S	0.971
10:89007756:T:A	C85S	0.969
10:89007757:G:C	C85S	0.969
10:89014260:A:C	Q273P	0.969
10:89014275:T:C	L278P	0.969
10:89007813:T:A	C104S	0.968
10:89007814:G:C	C104S	0.968
10:89008911:C:G	C119W	0.968
10:89014261:G:C	Q273H	0.968
10:89014261:G:T	Q273H	0.968

dbSNP variants (sampled 300 via entrez): RS1000075584 (10:88985458 CTA>C), RS1000126422 (10:89002991 G>C), RS1000156040 (10:88966603 A>G), RS1000226433 (10:88996145 G>A), RS1000262954 (10:89016782 C>A,T), RS1000298215 (10:89005207 A>G), RS1000502478 (10:89002643 A>C), RS1000580835 (10:88983730 G>A,C), RS1000614659 (10:89003487 T>C), RS1000617218 (10:88965227 T>C), RS1000624870 (10:88974112 G>GT), RS1000684472 (10:88976490 T>C), RS1000701669 (10:88963711 G>T), RS1000713502 (10:88976250 C>T), RS1000777587 (10:89012549 A>G)

Disease associations

OMIM: gene MIM:134637 | disease phenotypes: MIM:601859, MIM:611788

GenCC curated gene-disease

Disease	Classification	Inheritance
autoimmune lymphoproliferative syndrome type 1	Definitive	Autosomal dominant
autoimmune lymphoproliferative syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
FAS-related autoimmune lymphoproliferative immune disorder	Definitive	SD

Mondo (4): autoimmune lymphoproliferative syndrome type 1 (MONDO:0011158), aortic aneurysm, familial thoracic 6 (MONDO:0012730), autoimmune lymphoproliferative syndrome (MONDO:0017979), hepatoblastoma (MONDO:0018666)

Orphanet (2): Autoimmune lymphoproliferative syndrome (Orphanet:3261), Hepatoblastoma (Orphanet:449)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D056735	Autoimmune Lymphoproliferative Syndrome	C15.604.515.138; C16.320.089; C20.111.288; C20.683.515.124
D018197	Hepatoblastoma	C04.557.435.380
C567085	Aortic Aneurysm, Familial Thoracic 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523207 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Tumour necrosis factor (TNF) receptor family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Fluorouracil	increases activity, increases expression, increases reaction, affects cotreatment, decreases expression (+1 more)	21
Doxorubicin	increases reaction, decreases expression, increases response to substance, decreases reaction, increases expression (+5 more)	17
Arsenic Trioxide	affects cotreatment, affects reaction, increases cleavage, increases response to substance, decreases reaction (+1 more)	16
Cisplatin	affects binding, affects cotreatment, increases reaction, affects expression, increases phosphorylation (+6 more)	15
Benzo(a)pyrene	decreases methylation, decreases reaction, affects expression, affects cotreatment, increases expression (+1 more)	13
Tretinoin	decreases expression, decreases reaction, increases activity, affects cotreatment, increases expression	9
Resveratrol	increases reaction, increases response to substance, affects localization, affects binding, affects cotreatment (+3 more)	8
Aflatoxin B1	affects expression, decreases methylation, increases expression	7
bisphenol A	decreases expression, increases expression, affects cotreatment	6
sodium arsenite	decreases expression, increases expression	6
Vorinostat	affects cotreatment, increases expression, affects localization, decreases reaction, increases activity (+4 more)	6
Acetylcysteine	decreases expression, decreases reaction, increases expression, affects binding	6
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	6
Palmitic Acid	decreases expression, decreases reaction, increases expression, affects cotreatment, affects expression	6
Methotrexate	decreases reaction, increases expression, decreases expression	5
Quercetin	affects response to substance, increases expression	5
methylmercuric chloride	increases expression, affects cotreatment	4
trichostatin A	increases expression, increases reaction, affects cotreatment	4
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases expression, affects response to substance, decreases reaction, increases expression, increases reaction	4
Arsenic	affects methylation, increases expression, affects cotreatment, affects expression	4
Camptothecin	increases expression, affects cotreatment, decreases expression, increases activity, increases cleavage (+2 more)	4
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, decreases expression	4
Mitomycin	affects splicing, increases expression, increases secretion	4
Cadmium Chloride	increases expression, decreases expression	4
Oleic Acid	affects cotreatment, decreases reaction, increases expression	4
Particulate Matter	increases expression, decreases expression, increases abundance, affects expression	4
monomethylarsonous acid	increases expression, decreases expression	3
Bortezomib	affects cotreatment, increases expression, decreases expression	3
Zoledronic Acid	affects cotreatment, increases expression	3
Acetaminophen	decreases expression, increases expression	3

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4434525	Binding	Inhibition of s-CD95L(unknown origin)-stimulated cell migration of human MDA-MB-231 cells at 1 uM incubated for 24 hrs by Boyden chambers assay	Synthesis of peptidomimetics and chemo-biological tools for CD95/PLCγ1 interaction analysis. — Bioorg Med Chem Lett

Cellosaurus cell lines

9 cell lines: 7 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2CL	RSO4	Cancer cell line	Female
CVCL_B1RY	Abcam HeLa FAS KO	Cancer cell line	Female
CVCL_B8FT	Abcam HCT 116 FAS KO	Cancer cell line	Male
CVCL_B8VM	Abcam MCF-7 FAS KO	Cancer cell line	Female
CVCL_B9I0	Abcam A-549 FAS KO	Cancer cell line	Male
CVCL_D9EP	Ubigene HEK293 FAS KO	Transformed cell line	Female
CVCL_SN13	HAP1 FAS (-)	Cancer cell line	Male
CVCL_T422	Psi-CRIP-RxhFAS-i-CD80	Transformed cell line	Male
CVCL_VN49	KOB	Cancer cell line	Male

Clinical trials (associated diseases)

62 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03017326	PHASE3	ACTIVE_NOT_RECRUITING	Paediatric Hepatic International Tumour Trial
NCT03533582	PHASE3	ACTIVE_NOT_RECRUITING	Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
NCT04478292	PHASE3	RECRUITING	A Multi-institutional Study for Treatment of Children With Newly Diagnosed Hepatoblastoma Using a Modified PHITT Strategy
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT06730126	PHASE2	RECRUITING	Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients
NCT01154816	PHASE2	COMPLETED	Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia
NCT02011126	PHASE2	WITHDRAWN	Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT05302921	PHASE2	COMPLETED	Neoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors
NCT06638931	PHASE2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT07300449	PHASE2	RECRUITING	A Prospective Multicenter Clinical Study of SCCG Protocol and ctDNA 5hmc in Predicting the Chemotherapy Sensitivity and Monitoring the Recurrence and Metastasis of Hepatoblastoma in Children and Adolescents
NCT01331135	PHASE1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT02390843	PHASE1	COMPLETED	Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors
NCT03618381	PHASE1	ACTIVE_NOT_RECRUITING	EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04093648	PHASE1	WITHDRAWN	T Cells co- Expressing a Second Generation Glypican 3-specific Chimeric Antigen Receptor With Cytokines Interleukin-21 and 15 as Immunotherapy for Patients With Liver Cancer (TEGAR)
NCT04308330	PHASE1	RECRUITING	Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies
NCT04337177	PHASE1	ACTIVE_NOT_RECRUITING	Flavored, Oral Irinotecan VAL-413 (Orotecan®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors
NCT04483778	PHASE1	ACTIVE_NOT_RECRUITING	B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04897321	PHASE1	RECRUITING	B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)
NCT06198296	PHASE1	RECRUITING	Immunotherapy For Adults With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells
NCT07148050	PHASE1	RECRUITING	Immunotherapy for Solid Tumor Malignancies in Pediatrics Using Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor T Cells
NCT00392951	PHASE1/PHASE2	COMPLETED	Sirolimus for Autoimmune Disease of Blood Cells
NCT00605657	PHASE1/PHASE2	COMPLETED	Valproic Acid (Depakote[Registered Trademark]) to Treat Autoimmune Lymphoproliferative Syndrome (ALPS)
NCT01672918	Not specified	WITHDRAWN	Fluorodeoxyglucose Imaging Studies to Detect Lymphoma
NCT04902807	Not specified	RECRUITING	Conception of a Diagnosis, Prognosis and Therapeutic Decision Tool for Patients With Autoimmunity and Inflammation
NCT03728543	PHASE2/PHASE3	UNKNOWN	the Efficacy and Safety of Sugammadex in Children 0-2 Years Old