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
• GWAS associations: 21
• Clinical variants (ClinVar): 528 total — 72 pathogenic, 45 likely-pathogenic (top 6% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈9% of expected missense variation)
• GTEx eGene: eQTL in 38 tissues, sQTL in 25 (q < 0.05)
• Phenotypes (HPO): 187
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types (inferred from mutation patterns)
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.37 (moderately constrained)
• MANE Select transcript: NM_000043
• Interaction hub: 2,444 STRING partners (top 4% of genes corpus-wide)

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: 62 — 22 retained_intron, 20 protein_coding, 11 protein_coding_CDS_not_defined, 9 nonsense_mediated_decay

MANE Select: ENST00000652046

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 9, TSL 2: 1, TSL 3: 3, TSL 5: 6

ENST00000652046, ENST00000313771, ENST00000355279, ENST00000355740, ENST00000357339, ENST00000371857, ENST00000460510, ENST00000466081, ENST00000477270, ENST00000479522, ENST00000484444, ENST00000487314, ENST00000488877, ENST00000492756, ENST00000494410, ENST00000494799, ENST00000562983, ENST00000612663, ENST00000640140, ENST00000640250, ENST00000640681, 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, ENST00001140016

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.

Highest expression (Bgee): rectum, ovary, gall bladder, epithelium of nasopharynx, nasopharynx.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FAS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 38 tissues and its splicing (sQTL) in 25 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 63 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	eqtl	4.2e-62	-0.41	10:88996277:G:GT
Adrenal Gland	eqtl	8.4e-59	-0.93	10:89011095:C:T
Brain Caudate basal ganglia	eqtl	7.6e-50	-0.89	10:88991152:C:T
Muscle Skeletal	eqtl	4.0e-45	-0.35	10:88995196:T:G
Skin Not Sun Exposed Suprapubic	eqtl	7.1e-45	+0.46	10:88999856:A:G
Brain Nucleus accumbens basal ganglia	eqtl	3.8e-41	-0.83	10:88991152:C:T
Breast Mammary Tissue	eqtl	4.9e-40	-0.43	10:88996389:T:G
Nerve Tibial	eqtl	2.6e-39	-0.38	10:88996277:G:GT
Brain Cortex	eqtl	4.9e-39	+0.68	10:88991759:C:T
Brain Putamen basal ganglia	eqtl	7.7e-37	-0.74	10:88991152:C:T
Testis	sqtl	1.2e-32	+0.76	10:89002619:G:T
Esophagus Muscularis	eqtl	2.8e-32	-0.40	10:88991759:C:T
Brain Anterior cingulate cortex BA24	eqtl	3.4e-32	+0.71	10:88991759:C:T
Skin Sun Exposed Lower leg	eqtl	1.7e-29	+0.30	10:88999856:A:G
Esophagus Gastroesophageal Junction	eqtl	9.8e-28	+0.39	10:88999856:A:G
Adipose Visceral Omentum	eqtl	1.4e-26	+0.27	10:88999856:A:G
Brain Frontal Cortex BA9	eqtl	6.9e-25	+0.58	10:88991759:C:T
Brain Amygdala	eqtl	1.1e-24	-0.87	10:88991152:C:T
Cells EBV-transformed lymphocytes	sqtl	1.4e-21	-0.85	10:89011095:C:T
Lung	sqtl	2.5e-17	-0.42	10:88995843:C:CA

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

showing 100 of 294 tissues 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
endocervix	UBERON:0000458	91.02	gold quality
blood	UBERON:0000178	90.97	gold quality
palpebral conjunctiva	UBERON:0001812	90.88	gold quality
right coronary artery	UBERON:0001625	90.74	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.74	gold quality
omental fat pad	UBERON:0010414	90.43	gold quality
lung	UBERON:0002048	90.41	gold quality
peritoneum	UBERON:0002358	90.41	gold quality
parietal pleura	UBERON:0002400	90.33	gold quality
upper leg skin	UBERON:0004262	90.13	gold quality
ectocervix	UBERON:0012249	90.10	gold quality
popliteal artery	UBERON:0002250	90.07	gold quality
smooth muscle tissue	UBERON:0001135	90.06	gold quality
tibial artery	UBERON:0007610	90.06	gold quality
lymph node	UBERON:0000029	90.04	gold quality
artery	UBERON:0001637	90.04	gold quality
coronary artery	UBERON:0001621	89.82	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.78	gold quality
descending thoracic aorta	UBERON:0002345	89.49	gold quality
pleura	UBERON:0000977	89.47	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.46	gold quality
aorta	UBERON:0000947	89.12	gold quality
colonic epithelium	UBERON:0000397	88.95	gold quality
skin of hip	UBERON:0001554	88.83	gold quality
cervix squamous epithelium	UBERON:0006922	88.62	gold quality
uterine cervix	UBERON:0000002	88.36	gold quality
skin of abdomen	UBERON:0001416	88.29	gold quality
blood vessel layer	UBERON:0004797	88.16	gold quality
thoracic aorta	UBERON:0001515	88.14	gold quality
ascending aorta	UBERON:0001496	88.12	gold quality
transverse colon	UBERON:0001157	88.07	gold quality
tibial nerve	UBERON:0001323	87.93	gold quality
lower lobe of lung	UBERON:0008949	87.91	gold quality
large intestine	UBERON:0000059	87.85	gold quality
vagina	UBERON:0000996	87.73	gold quality
mucosa of stomach	UBERON:0001199	87.68	gold quality
bone marrow	UBERON:0002371	87.68	gold quality
granulocyte	CL:0000094	87.65	gold quality
colon	UBERON:0001155	87.60	gold quality
fallopian tube	UBERON:0003889	87.41	gold quality
caecum	UBERON:0001153	87.26	gold quality
sigmoid colon	UBERON:0001159	87.11	gold quality
visceral pleura	UBERON:0002401	87.11	gold quality
female reproductive system	UBERON:0000474	87.10	gold quality
intestine	UBERON:0000160	86.90	gold quality
uterus	UBERON:0000995	86.88	gold quality
ventricular zone	UBERON:0003053	86.78	gold quality
decidua	UBERON:0002450	86.77	gold quality
mucosa of transverse colon	UBERON:0004991	86.62	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.55	gold quality
esophagus mucosa	UBERON:0002469	86.36	gold quality
cervix epithelium	UBERON:0004801	86.32	gold quality
oral cavity	UBERON:0000167	86.23	gold quality
esophagus	UBERON:0001043	86.22	gold quality
squamous epithelium	UBERON:0006914	86.15	gold quality
zone of skin	UBERON:0000014	86.05	gold quality
bronchial epithelial cell	CL:0002328	86.01	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.97	gold quality
lower esophagus	UBERON:0013473	85.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.95	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.94	gold quality
endometrium	UBERON:0001295	85.85	gold quality
myometrium	UBERON:0001296	85.79	gold quality
spleen	UBERON:0002106	85.77	gold quality
urinary bladder	UBERON:0001255	85.72	gold quality
endometrium epithelium	UBERON:0004811	85.72	silver quality
right atrium auricular region	UBERON:0006631	85.62	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.59	gold quality
esophagus squamous epithelium	UBERON:0006920	85.55	gold quality
gingiva	UBERON:0001828	85.54	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Liver	tissue	12.0
Bone marrow	tissue	10.7
Thymus	tissue	9.0
Lymph node	tissue	8.9
Ovary	tissue	8.7
Adrenal gland	tissue	8.7
Lung	tissue	8.2
Rectum	tissue	7.7
Fallopian tube	tissue	7.5
Vagina	tissue	7.4
Cerebral cortex	tissue	7.2
Smooth muscle	tissue	7.2
Olfactory bulb	tissue	7.2
Retrosplenial cortex	tissue	7.2
Colon	tissue	7.0
Cerebellum	tissue	6.6
Hippocampus	tissue	6.5
Appendix	tissue	6.5
Retrosplenial and cingulate cortex	tissue	6.3
Prefrontal cortex	tissue	6.0
Putamen	tissue	6.0
Nucleus accumbens	tissue	6.0
Corpus callosum	tissue	6.0
Postcentral gyrus	tissue	6.0
Insular cortex	tissue	6.0
Gallbladder	tissue	5.9
Occipital cortex	tissue	5.9
Spinal cord	tissue	5.8
Tonsil	tissue	5.7
Basal ganglia	tissue	5.6
Medulla oblongata	tissue	5.6
Locus coeruleus	tissue	5.6
Amygdala	tissue	5.4
Hippocampal formation	tissue	5.4
Entorhinal cortex	tissue	5.4
Somatosensory cortex	tissue	5.4
Substantia nigra	tissue	5.3
Temporal cortex	tissue	5.3
Endometrium 1	tissue	5.2
Motor cortex	tissue	5.2
Choroid plexus	tissue	5.2
Esophagus	tissue	4.9
Placenta	tissue	4.9
Ventral forebrain	tissue	4.9
Cervix	tissue	4.7
Adipose tissue	tissue	4.7
Septum	tissue	4.7
Thalamus	tissue	4.6
Superior colliculi	tissue	4.6
Midbrain	tissue	4.5
Pons	tissue	4.3
Urinary bladder	tissue	4.3
Hypothalamus	tissue	4.3
Spleen	tissue	4.3
Periaqueductal gray	tissue	4.3
Seminal vesicle	tissue	3.9
Breast	tissue	3.8
Small intestine	tissue	3.5
Prostate	tissue	3.3
Skin 1	tissue	2.7

Brain sub-regions (HPA Brain Atlas): detected in 288; highest nTPM — Flocculonodular lobe (389.7), Nucleus ambiguus (387.1), Nucleus raphe magnus (376.1), Angular gyrus (white matter) (369.7), Nuclei of the trapezoid body (367.2).

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)

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

showing 30 of 116 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.372, missense Z 1.26 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000652046 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈9% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
10:88,990,877–89,014,218	276 / 300.1	0.92	no
10:89,014,219–89,014,303	11 / 33.2	0.33	yes (p 1.1e-04)
10:89,014,304–89,014,447	52 / 52.7	0.99	no
ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

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

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cd27	ENSDARG00000105423
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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95484) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 185 distinct phenotype terms.

Mouse phenotype (MP)	Records
enlarged lymph nodes	20
increased anti-nuclear antigen antibody level	15
premature death	14
glomerulonephritis	14
enlarged spleen	11
increased anti-double stranded DNA antibody level	11
increased immunoglobulin level	9
increased autoantibody level	9
increased IgG level	7
increased IgM level	6
renal glomerular immunoglobulin deposits	6
increased urine protein level	5
increased anti-single stranded DNA antibody level	5
autoimmune response	4
abnormal hypersensitivity reaction	4
increased double-negative T cell number	4
lymph node hyperplasia	4
increased IgG1 level	4
increased IgG2a level	4
abnormal stria vascularis morphology	3
skin lesions	3
salivary gland inflammation	3
increased spleen weight	3
increased lymphocyte cell number	3
abnormal renal glomerulus morphology	3

+160 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
Macaca nemestrina	Q9BDN0	98.5%	Diamond
Macaca fascicularis	Q9TSN4	98.5%	Diamond
Cercocebus atys	Q9BDN4	97.6%	Diamond
Macaca mulatta	Q9BDP2	94.3%	Diamond
Sus scrofa	O77736	62.8%	Diamond
Bos taurus	P51867	62.6%	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
FAS-AS1	ncRNA	100302740
STAMBPL1	protein-coding	57559
ACTA2	protein-coding	59
ACTA2-AS1	ncRNA	100132116
MIR4679-1	ncRNA	100616128
MIR4679-2	ncRNA	100616192
ANKRD22	protein-coding	118932
LIPM	protein-coding	340654

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): A0A087WTM9, A0A8Q3SIR6, A0A8Q3SIY4, A0A8Q3SJI5, A0A8Q3WLI5, A0A8Q3WLK1, A0A8Q3WLK6, A0A8Q3WLL4, A0A8Q3WM13, A0A8V8TKJ0, A0A8V8TKN4, A0A8V8TM64, P25445, 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 (101 total): sequence variant 36, splice variant 11, helix 9, disulfide bond 8, mutagenesis site 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 by resolution:

PDB	Title	Method	Resolution (Å)
3TJE	Crystal structure of Fas receptor extracellular domain in complex with Fab E09	X-RAY DIFFRACTION	1.93
3THM	Crystal structure of Fas receptor extracellular domain in complex with Fab EP6b_B01	X-RAY DIFFRACTION	2.1
3EWT	Crystal Structure of calmodulin complexed with a peptide	X-RAY DIFFRACTION	2.4
3EZQ	Crystal Structure of the Fas/FADD Death Domain Complex	X-RAY DIFFRACTION	2.73
9NCQ	Cryo-EM structure of Fas-FADD complex	ELECTRON MICROSCOPY	3.51
1DDF	FAS DEATH DOMAIN, NMR, MINIMIZED AVERAGE STRUCTURE	SOLUTION NMR
2NA7	Transmembrane domain of human Fas/CD95 death receptor	SOLUTION NMR

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 3THM, 3TJE

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted secreted proteins, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers, Candidate cardiovascular disease genes, Disease related genes, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; cytosol; nuclear bodies

Antibody reliability (HPA): IH uncertain · IF supported

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)

Type	Positions
Phosphoserine	209, 225
Phosphothreonine	214
S-palmitoyl cysteine	199

Disulfide bonds (8)

Type	Positions
Disulfide bond	59–73, 63–82, 85–101, 104–119, 107–127, 129–143, 146–157, 149–165

Glycosylation sites (4)

Type	Positions
O-linked (galnac…) threonine	28
N-linked (glcnac…) asparagine	118, 136
(microbial infection) n-beta-linked (glcnac) arginine	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 curated (TAS) of 19; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

19 pathways:

ID	Pathway	Evidence
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-75157	FasL/ CD95L signaling	curated
R-HSA-5213460	RIPK1-mediated regulated necrosis	curated
R-HSA-3371378	Regulation by c-FLIP	curated
R-HSA-6803211	TP53 Regulates Transcription of Death Receptors and Ligands	curated
R-HSA-109581	Apoptosis	—
R-HSA-5357769	Caspase activation via extrinsic apoptotic signalling pathway	—
R-HSA-73887	Death Receptor Signaling	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
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-5633008	TP53 Regulates Transcription of Cell Death Genes	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

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 (10): cytosol (GO:0005829), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), 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

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
TP53 Regulates Transcription of Cell Death Genes	1
Death Receptor Signaling	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Apoptosis	1
Transcriptional Regulation by TP53	1
RIPK1-mediated regulated necrosis	1
Gene expression (Transcription)	1
Signal Transduction	1

GO top-level categories

showing 60 of 63 GO namespaces:

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
positive regulation of reactive oxygen species metabolic process	1
positive regulation of signal transduction	1
positive regulation of apoptotic process	1
regulation of apoptotic signaling pathway	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
death receptor activity	1
tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor binding	1
enzyme binding	1
molecular transducer activity	1
signaling receptor activity	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
plasma membrane protein complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 22 of 37 annotations. The rest are phylogenetic / computational / electronic (IEA).

22 experimentally-supported GO terms:

GO term	NS	Evidence
Fas signaling pathway	BP	direct assay
apoptotic process	BP	direct assay
cellular response to amino acid starvation	BP	mutant phenotype
cellular response to hyperoxia	BP	mutant phenotype
cellular response to mechanical stimulus	BP	expression pattern
extrinsic apoptotic signaling pathway	BP	mutant phenotype
extrinsic apoptotic signaling pathway via death domain receptors	BP	direct assay
necroptotic signaling pathway	BP	mutant phenotype
positive regulation of apoptotic process	BP	direct assay
positive regulation of apoptotic signaling pathway	BP	mutant phenotype
positive regulation of reactive oxygen species biosynthetic process	BP	direct assay
regulation of stress-activated MAPK cascade	BP	mutant phenotype
CD95 death-inducing signaling complex	CC	direct assay
cell surface	CC	direct assay
death-inducing signaling complex	CC	direct assay
extracellular exosome	CC	high-throughput assay
membrane raft	CC	direct assay
plasma membrane	CC	direct assay
calmodulin binding	MF	direct assay
identical protein binding	MF	physical interaction
kinase binding	MF	physical interaction
tumor necrosis factor receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,444 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAS	FASLG	P48023	940
FAS	FADD	Q13158	894
FAS	CASP8	Q14790	894
FAS	TNFRSF1A	P19438	868
FAS	TNF	P01375	849
FAS	CASP3	P42574	848
FAS	CD4	P01730	829
FAS	CD8A	P01732	829
FAS	CD27	P26842	799
FAS	CFLAR	O15519	787
FAS	TNFSF10	P50591	781
FAS	CASP9	P55211	775
FAS	CASP10	Q92851	766
FAS	CYCS	P00001	763
FAS	TRADD	Q15628	743

IntAct

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

showing 30 of 44 partners by confidence:

Partner	Interaction type	MIscore	Records
FADD	physical association	0.960	20
CASP8	physical association	0.920	6
FASLG	association	0.760	5
DAXX	physical association	0.670	3
PTPN13	physical association	0.590	3
CALM1	physical association	0.580	4
PML-RAR	physical association	0.580	3
MAP3K5	physical association	0.540	2
PML	physical association	0.520	4
CAV1	colocalization	0.460	3
SRC	physical association	0.400	2
PDCD6	physical association	0.400	1
YES1	physical association	0.400	1
APOA5	physical association	0.370	1
ATP6V0B	physical association	0.370	1
BAG6	physical association	0.370	1
CCND3	physical association	0.370	1
GADD45A	physical association	0.370	1
HNRNPC	physical association	0.370	1
MBD4	physical association	0.370	1
RIPK1	physical association	0.370	1
SUMO1	physical association	0.370	1
TCAP	physical association	0.370	1
TMX1	physical association	0.370	1
UBQLN1	physical association	0.370	1
CFLAR	association	0.350	6
FYN	colocalization	0.350	1
INPP5D	association	0.350	1
PEX1	association	0.350	1
AKT1	proximity	0.270	1

BioGRID (518 interactions; top human partners by supporting records): FADD (Affinity Capture-MS; 25 records), CASP8 (Affinity Capture-MS; 14 records), DAXX (Co-localization; 11 records), FASLG (Co-localization; 7 records), UBAC1 (Proximity Label-MS; 6 records), FAF1 (Affinity Capture-Western; 5 records), RELA (Proximity Label-MS; 4 records), SPATA5L1 (Affinity Capture-MS; 4 records), TRIP6 (Affinity Capture-Western; 4 records), TUBB2A (Affinity Capture-MS; 4 records), TUBB2B (Affinity Capture-MS; 4 records), UBE2I (Affinity Capture-Western; 4 records), ARF5 (Affinity Capture-MS; 3 records), C17orf75 (Affinity Capture-MS; 3 records), C19orf52 (Affinity Capture-MS; 3 records)

SIGNOR signaling

showing 14 of 16 signaling 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”

Protein complexes (CORUM) (6)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

6 complexes by size:

Complex	Subunits	Members
DISC complex (FAS, FADD, CASP8, CFLAR), membrane-associated, CD95L induced	4	CASP8, CFLAR, FADD, FAS
CASP8-CASP10-FADD-FAS complex	4	FAS, CASP10, CASP8, FADD
DISC complex (FAS, FADD, CASP8)	3	CASP8, FADD, FAS
CASP10-FADD-FAS complex	3	CASP10, FADD, FAS
FAS-TNFSF13 complex	2	FAS, TNFSF13
CD40-FAS complex	2	CD40, FAS

Ligand–receptor pairs (CellPhoneDB) (1)

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

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
FASLG	receptor	Signaling by Tumor necrosis factor

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 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
RIPK1-mediated regulated necrosis	5	57.1×	3e-06
Signaling by ERBB2	5	43.3×	8e-06
VEGFA-VEGFR2 Pathway	7	24.4×	2e-06
Diseases of signal transduction by growth factor receptors and second messengers	6	8.5×	1e-03
Signaling by Receptor Tyrosine Kinases	6	7.8×	1e-03
Cytokine Signaling in Immune system	7	7.1×	8e-04
Hemostasis	6	5.4×	7e-03
Infectious disease	7	4.3×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of extrinsic apoptotic signaling pathway	6	63.5×	1e-07
extrinsic apoptotic signaling pathway via death domain receptors	6	56.0×	2e-07
T cell costimulation	5	43.5×	1e-05
extrinsic apoptotic signaling pathway	6	42.8×	1e-06
apoptotic signaling pathway	8	41.8×	1e-08
positive regulation of neuron apoptotic process	5	31.6×	4e-05
negative regulation of angiogenesis	5	19.6×	4e-04
MAPK cascade	5	17.8×	6e-04

Disease & clinical

Cancer significance

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

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for FAS: 528 ClinVar records (117 pathogenic / likely pathogenic); 21 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	72
Likely pathogenic	45
Uncertain significance	227
Likely benign	101
Benign	32

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 117 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
872242	NM_000043.6(FAS):c.46_47del (p.Val15_Ala16insTer)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
16514	NM_000043.6(FAS):c.651+2T>C	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1457614	NM_000043.6(FAS):c.528G>A (p.Trp176Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
265400	NM_000043.6(FAS):c.879_880del (p.Leu294fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1067934	NM_000043.6(FAS):c.778G>A (p.Asp260Asn)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3765194	NM_000043.6(FAS):c.586C>T (p.Gln196Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
860668	NM_000043.6(FAS):c.776T>C (p.Ile259Thr)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2136913	NM_000043.6(FAS):c.404G>A (p.Cys135Tyr)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2573797	NM_000043.6(FAS):c.794A>G (p.Asp265Gly)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3370437	NM_000043.6(FAS):c.748C>G (p.Arg250Gly)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
16505	NM_000043.6(FAS):c.749G>C (p.Arg250Pro)	Pathogenic	criteria provided, single submitter	4
16498	NM_000043.6(FAS):c.334+2dup	Pathogenic	criteria provided, single submitter	2
16501	NM_000043.6(FAS):c.817C>T (p.Gln273Ter)	Pathogenic	criteria provided, single submitter	2
16504	NM_000043.6(FAS):c.779A>T (p.Asp260Val)	Pathogenic	criteria provided, single submitter	2
2130948	NM_000043.6(FAS):c.676+1G>C	Pathogenic	criteria provided, single submitter	2

Per-variant reference — Sugi Variant

Explore FAS’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; 30 predictions of 895):

Position(s)	Effect	Δscore	Sites
10:88990907–88990908	donor_loss	1.0000	5
10:89003027–89003028	acceptor_loss	1.0000	6
10:89003195–89003196	donor_loss	1.0000	4
10:89010537	acceptor_loss	1.0000
10:89010598	donor_gain	1.0000
10:89010601–89010602	donor_loss	1.0000	4
10:89011631–89011632	acceptor_gain	1.0000	2
10:89014117–89014118	acceptor_loss	1.0000	5
10:89003195	donor_loss	0.9900
10:89008124	acceptor_gain	0.9900

AlphaMissense

393 missense substitutions predicted likely pathogenic (of 2,224 scored), across 110 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
D260	8	0.821	0.931
D108	8	0.746	0.817
W281	7	0.961	0.985
C119	7	0.948	0.972
C107	7	0.941	0.971
C85	7	0.940	0.969
C129	7	0.933	0.974
C143	7	0.925	0.958
C104	7	0.924	0.968
C135	7	0.923	0.946
C127	7	0.921	0.973
C101	7	0.911	0.964
M240	7	0.906	0.962
C63	7	0.896	0.934
C157	7	0.881	0.943
C146	7	0.872	0.910
C140	7	0.867	0.915
F134	7	0.860	0.973
E272	7	0.842	0.926
C82	7	0.822	0.890

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

6 prognostic cancer types:

Cancer	Prognostic	p-value
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	8.58e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.96e-05
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000139
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.000284
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	0.000388
Glioblastoma Multiforme (validation)	unfavorable	0.000697

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
autoimmune lymphoproliferative syndrome type 1	Definitive	Autosomal dominant	3
autoimmune lymphoproliferative syndrome	Definitive	Autosomal dominant	4

ClinGen Gene-Disease Validity

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

1 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
Autoimmune lymphoproliferative syndrome with defective apoptosis	green
COVID-19 research	green
Cytopenia - NOT Fanconi anaemia	green
Fetal anomalies	green
Haematological malignancies cancer susceptibility	green
Haematological malignancies for rare disease	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (2): autoimmune lymphoproliferative syndrome type 1 (MONDO:0011158), autoimmune lymphoproliferative syndrome (MONDO:0017979)

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

HPO phenotypes

showing 60 of 187 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000031	Epididymitis
HP:0000083	Renal insufficiency
HP:0000099	Glomerulonephritis
HP:0000155	Oral ulcer
HP:0000360	Tinnitus
HP:0000407	Sensorineural hearing impairment
HP:0000488	Retinopathy
HP:0000499	Abnormal eyelash morphology
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000541	Retinal detachment
HP:0000554	Uveitis
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000622	Blurred vision
HP:0000708	Atypical behavior
HP:0000737	Irritability
HP:0000854	Thyroid adenoma
HP:0000978	Bruising susceptibility
HP:0001025	Urticaria
HP:0001045	Vitiligo
HP:0001053	Hypopigmented skin patches
HP:0001061	Acne
HP:0001094	Iridocyclitis
HP:0001097	Keratoconjunctivitis sicca
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001269	Hemiparesis
HP:0001287	Meningitis
HP:0001288	Gait disturbance
HP:0001289	Confusion
HP:0001347	Hyperreflexia
HP:0001369	Arthritis
HP:0001402	Hepatocellular carcinoma
HP:0001482	Subcutaneous nodule
HP:0001596	Alopecia
HP:0001637	Abnormal myocardium morphology
HP:0001653	Mitral regurgitation
HP:0001658	Myocardial infarction
HP:0001659	Aortic regurgitation
HP:0001701	Pericarditis
HP:0001733	Pancreatitis
HP:0001744	Splenomegaly
HP:0001789	Hydrops fetalis
HP:0001824	Weight loss
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:0001945	Fever
HP:0001954	Recurrent fever
HP:0001971	Hypersplenism
HP:0001973	Autoimmune thrombocytopenia
HP:0002014	Diarrhea

GWAS associations

21 associations:

Study	Trait	p-value
GCST009731_7	Blood protein levels in cardiovascular risk	2e-28
GCST006585_2533	Blood protein levels	2e-24
GCST006585_2704	Blood protein levels	3e-21
GCST006585_2276	Blood protein levels	4e-18
GCST004146_14	Chronic lymphocytic leukemia	1e-15
GCST002073_3	Chronic lymphocytic leukemia	1e-14
GCST003468_11	Chronic lymphocytic leukemia	9e-14
GCST90002403_408	Red blood cell count	4e-13
GCST90002397_724	Mean spheric corpuscular volume	1e-12
GCST90002392_694	Mean corpuscular volume	4e-12
GCST002299_13	Chronic lymphocytic leukemia	2e-8
GCST005528_16	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	3e-8
GCST003814_2	Selective IgA deficiency	7e-8
GCST000852_5	Atrioventricular conduction	7e-7
GCST004863_8	Mosquito bite size	2e-6
GCST001762_359	Obesity-related traits	5e-6
GCST007844_16	Ankylosing spondylitis	5e-6
GCST000763_3	Immunoglobulin A	6e-6
GCST001762_183	Obesity-related traits	7e-6
GCST001762_585	Obesity-related traits	7e-6
GCST001762_517	Obesity-related traits	9e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0004747	protein measurement
EFO:0004338	body weight
EFO:0004340	body mass index
EFO:0008378	mosquito bite reaction size measurement
EFO:0010610	tumor necrosis factor receptor superfamily member 6 measurement
EFO:0004305	erythrocyte count

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): CHEMBL4523207 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

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 expression, increases reaction, affects cotreatment, decreases expression, affects reaction (+1 more)	21
Doxorubicin	increases response to substance, decreases reaction, affects expression, affects cotreatment, increases activity (+5 more)	17
Arsenic Trioxide	decreases reaction, increases expression, affects cotreatment, affects reaction, increases cleavage (+1 more)	16
Cisplatin	increases expression, affects localization, increases stability, decreases reaction, affects expression (+6 more)	15
Benzo(a)pyrene	affects cotreatment, increases expression, decreases expression, decreases methylation, decreases reaction (+1 more)	13
Tretinoin	decreases reaction, increases activity, affects cotreatment, increases expression, decreases expression	9
Resveratrol	affects cotreatment, increases expression, increases reaction, increases localization, increases response to substance (+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 binding, increases reaction, increases phosphorylation (+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	affects cotreatment, affects expression, decreases expression, decreases reaction, increases expression	6
Methotrexate	decreases reaction, increases expression, decreases expression	5
Quercetin	affects response to substance, increases expression	5
Particulate Matter	decreases expression, increases abundance, affects expression, 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	increases reaction, decreases expression, affects response to substance, decreases reaction, increases expression	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	decreases expression, increases 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
monomethylarsonous acid	decreases expression, increases 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)

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

showing 60 of 93 trials:

NCT	Phase	Status	Title
NCT01574313	Phase 4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	Phase 4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	Phase 4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT02933333	Phase 4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03664674	Phase 3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	Phase 3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	Phase 3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT03017326	Phase 3	ACTIVE_NOT_RECRUITING	Paediatric Hepatic International Tumour Trial
NCT03533582	Phase 3	ACTIVE_NOT_RECRUITING	Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
NCT04478292	Phase 3	RECRUITING	A Multi-institutional Study for Treatment of Children With Newly Diagnosed Hepatoblastoma Using a Modified PHITT Strategy
NCT01821781	Phase 2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT06730126	Phase 2	RECRUITING	Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients
NCT05420350	Phase 2	UNKNOWN	Lamotrigine and Bupropion for Meniere’s Disease
NCT06544434	Phase 2	UNKNOWN	Laser Acupuncture for Meniere Disease
NCT01154816	Phase 2	COMPLETED	Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia
NCT02011126	Phase 2	WITHDRAWN	Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors
NCT02867592	Phase 2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	Phase 2	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	Phase 2	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	Phase 2	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	Phase 2	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	Phase 2	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	Phase 2	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	Phase 2	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	Phase 2	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	Phase 2	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	Phase 2	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	Phase 2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	Phase 2	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	Phase 2	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	Phase 2	COMPLETED	Neoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors
NCT06638931	Phase 2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT07300449	Phase 2	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
NCT04674735	Phase 1	WITHDRAWN	Safety of APSLXR in Patients Presenting Vertigo of Vestibular Origin or Meniere’s Disease
NCT01331135	Phase 1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT02390843	Phase 1	COMPLETED	Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors
NCT03618381	Phase 1	ACTIVE_NOT_RECRUITING	EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04093648	Phase 1	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	Phase 1	RECRUITING	Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies
NCT04337177	Phase 1	ACTIVE_NOT_RECRUITING	Flavored, Oral Irinotecan VAL-413 (Orotecan®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors
NCT04483778	Phase 1	ACTIVE_NOT_RECRUITING	B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04897321	Phase 1	RECRUITING	B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)
NCT06198296	Phase 1	RECRUITING	Immunotherapy For Adults With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells
NCT07148050	Phase 1	RECRUITING	Immunotherapy for Solid Tumor Malignancies in Pediatrics Using Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor T Cells
NCT00392951	Phase 1/2	COMPLETED	Sirolimus for Autoimmune Disease of Blood Cells
NCT00605657	Phase 1/2	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	COMPLETED	Conception of a Diagnosis, Prognosis and Therapeutic Decision Tool for Patients With Autoimmunity and Inflammation
NCT04218123	Phase 2/3	COMPLETED	Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere’s Disease Outcomes
NCT04766853	Phase 1/2	COMPLETED	Verification of the Efficacy/safety of the Intratympanic Drug Delivery for Hearing Loss
NCT04794842	Early Phase 1	UNKNOWN	Comparing Topical Tetracaine Drops to Topical Focal Phenol for Local Anesthesia During Intratympanic Steroid Injection
NCT00599560	Not specified	COMPLETED	Vasopressin and V2 Receptor in Meniere’s Disease
NCT02371798	Not specified	WITHDRAWN	Unilateral Meniere Disease: Can Double Dose Gadolinium and Delayed Imaging Make the Diagnosis?
NCT03520322	Not specified	TERMINATED	A Study of a Mastoid Device in Subjects With Ménière’s Disease
NCT03795675	Not specified	ACTIVE_NOT_RECRUITING	CI Following VS Removal or Labyrinthectomy
NCT04370366	Not specified	UNKNOWN	Imaging of Endolymphatic Hydrops at 7T MRI
NCT04569175	Not specified	COMPLETED	Non Enhanced Labyrinth Imaging for the Detection of Endolymphatic Hydrops in Meniere’s Disease NELI Study
NCT04686695	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation Treatment on Meniere Disease
NCT04835688	Not specified	UNKNOWN	Ventilation Tube Insertion for Unilateral Menière’s Disease
NCT04902963	Not specified	COMPLETED	What is the Tympanic Membrane Healing Time After Insertion of a Gelfoam PE Tube?