TNFRSF1A

Summary

TNFRSF1A (TNF receptor superfamily member 1A, HGNC:11916) is a protein-coding gene on chromosome 12p13.31, encoding Tumor necrosis factor receptor superfamily member 1A (P19438). Receptor for TNFSF2/TNF and homotrimeric TNFSF1/lymphotoxin-alpha.

This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients.

Source: NCBI Gene 7132 — RefSeq curated summary.

At a glance

• Gene–disease (curated): TNF receptor 1-associated periodic fever syndrome (Definitive, ClinGen)
• GWAS associations: 35
• Clinical variants (ClinVar): 633 total — 15 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 59
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001065

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11916
Approved symbol	TNFRSF1A
Name	TNF receptor superfamily member 1A
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	TNF-R, TNFAR, TNFR60, TNF-R-I, CD120a, TNF-R55
Ensembl gene	ENSG00000067182
Ensembl biotype	protein_coding
OMIM	191190
Entrez	7132

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 12 protein_coding, 7 nonsense_mediated_decay, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000162749, ENST00000366159, ENST00000437813, ENST00000440083, ENST00000534885, ENST00000535038, ENST00000535958, ENST00000536194, ENST00000537842, ENST00000538363, ENST00000539372, ENST00000540022, ENST00000543048, ENST00000543995, ENST00000698337, ENST00000698338, ENST00000698339, ENST00000698340, ENST00000898686, ENST00000898687, ENST00000898688, ENST00000898689, ENST00000947891, ENST00000947892, ENST00000947893

RefSeq mRNA: 3 — MANE Select: NM_001065 NM_001065, NM_001346091, NM_001346092

CCDS: CCDS8542

Canonical transcript exons

ENST00000162749 — 10 exons

Exon	Start	End
ENSE00003460621	6329778	6330066
ENSE00003464937	6330853	6330926
ENSE00003518282	6333737	6333865
ENSE00003524766	6334091	6334244
ENSE00003594635	6328771	6329622
ENSE00003621263	6333367	6333516
ENSE00003624410	6330267	6330295
ENSE00003632441	6333069	6333147
ENSE00003652096	6330598	6330711
ENSE00003896976	6341776	6342076

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 106.4715 / max 1087.5234, expressed in 1809 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129072	43.6436	1788
129070	30.5682	1775
129069	25.5871	1694
129071	4.0614	1615
129067	1.2152	749
129066	0.5879	324
129064	0.4353	228
129063	0.1931	64
129065	0.1798	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.98	gold quality
gall bladder	UBERON:0002110	98.77	gold quality
left uterine tube	UBERON:0001303	98.54	gold quality
omental fat pad	UBERON:0010414	98.53	gold quality
peritoneum	UBERON:0002358	98.52	gold quality
colonic epithelium	UBERON:0000397	98.42	gold quality
right coronary artery	UBERON:0001625	98.41	gold quality
upper lobe of left lung	UBERON:0008952	98.37	gold quality
descending thoracic aorta	UBERON:0002345	98.32	gold quality
left adrenal gland cortex	UBERON:0035825	98.32	gold quality
left adrenal gland	UBERON:0001234	98.30	gold quality
pericardium	UBERON:0002407	98.29	gold quality
blood	UBERON:0000178	98.22	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.22	gold quality
smooth muscle tissue	UBERON:0001135	98.18	gold quality
adrenal cortex	UBERON:0001235	98.12	gold quality
right lobe of thyroid gland	UBERON:0001119	98.08	gold quality
left coronary artery	UBERON:0001626	98.08	gold quality
lower esophagus	UBERON:0013473	98.08	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.08	gold quality
coronary artery	UBERON:0001621	98.07	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.06	gold quality
right adrenal gland	UBERON:0001233	98.05	gold quality
ascending aorta	UBERON:0001496	98.05	gold quality
thoracic aorta	UBERON:0001515	98.05	gold quality
body of uterus	UBERON:0009853	98.05	gold quality
right lung	UBERON:0002167	98.04	gold quality
ectocervix	UBERON:0012249	98.04	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.03	gold quality
upper lobe of lung	UBERON:0008948	98.02	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	16.96
E-CURD-112	yes	5.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CEBPA, CEBPB, CEBPG, ESR1, ETV4, FOXO3, IRF6, NCOA2, NFKB1, NFKB, NR1I2, REL, RELA, STAT1, TP53

miRNA regulators (miRDB)

27 targeting TNFRSF1A, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-6871-3P	99.43	68.85	741
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-585-5P	97.54	69.02	955
HSA-MIR-2278	97.30	66.19	1130
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-4280	96.44	67.69	473

Literature-anchored findings (GeneRIF, showing 40)

• Despite the presence of functional TNFR2, TNFR1 associated with MAPK-dependent and -independent pathways is the primary signaling pathway involved in TNF alpha-induced synthetic functions in ASM cells. (PMID:11562425)
• Here we report the expression and purification of the human TNF-RI DD as a fusion with the Escherichia coli thioredoxin A (TRX) protein (PMID:11676596)
• induced marked apoptosis in T cells from HIV-infected persons; associated with both alteration of Bcl-2 expression and activation of caspase-8 and caspase-3 (PMID:11861282)
• insulin resistance and blood pressure are linked to altered shedding of TNF-alpha receptors in type 2 diabetes mellitus (PMID:11882518)
• Autoimmune thyroid disease induced by thyroglobulin and lipopolysaccharide is inhibited by soluble TNF receptor type I. (PMID:11920568)
• The human papillomavirus 16 E6 protein binds to tumor necrosis factor (TNF) R1 and protects cells from TNF-induced apoptosis (PMID:11934887)
• Amino acid sequences located within an appropriately folded and functionally active death domain of the TNF receptor CD120a are both necessary and sufficient to promote the localization of the receptor to lipid rafts. (PMID:11937569)
• Soluble TNF-alpha receptor I is an extracellular domain of TNFRI and antagonizes activities of TNF-alpha. Local transfection of the sTNFRI gene may have potential therapeutic value in vascular diseases in which TNF-alpha is also usually highly expressed. (PMID:11947900)
• Altered signaling of TNFalpha-TNFR1 and SODD/BAG4 is responsible for radioresistance in human HT-R15 cells. (PMID:12017295)
• mutation spectrum in genes in patients suffering from AA amyloidosis and recurrent inflammatory attacks (PMID:12105243)
• Impaired glucose tolerance is not associated with increased serum concentrations. (PMID:12107724)
• candidate genes that may be involved in the origination of ameloblastoma and several genes previously unidentified in relation to human tooth development. (PMID:12147741)
• TNFRSF1A mutations were found in 28(7.1%) of 394 unrelated patients with tumor necrosis factor receptor-associated syndrome who have recurrent inflammatory syndromes. (PMID:12209523)
• Review. p55TNFR is required for secondary lymphoid organ architecture & optimal antibody responses to T-dependent antigens. It has an enhancing role in antigen-specific T4 cell priming. (PMID:12220546)
• Both adipose tissue and blood PAI-1 levels were positively associated with TNFRSF1A and TNFRSF1B in obesity. (PMID:12353079)
• Increased sTNFRs-p55 levels in the serum and ascitic fluid reflect abnormal immune status of the patients with HCC and help predict the development of tumor. (PMID:12376300)
• The role of TNF-R55 in the signaling pathway of neutral sphingomyelinase activation is enhanced by the interaction of RACK1 and FAN. (PMID:12391233)
• Elevated serum levels of soluble TNF-alpha receptor type I are strongly associated with the development of acute renal failure in patients with septic shock. (PMID:12500222)
• serum levels elevated in asthmatic patients during acute attack (PMID:12530121)
• TNFR1 gene region might be a susceptible locus to type 1 diabetes in Japanese. Aberrant expresison or function of the receptor could be involved in the development of the disease. (PMID:12559634)
• Polymorphism not associated with narcolepsy. (PMID:12601524)
• Plasma sTNFR1 and sTNFR2 were inversely related to insulin sensitivity and might contribute to the development of insulin resistance in glucose-intolerant subjects. (PMID:12610052)
• TNFR1 promoter polymorphisms are not associated with hereditary, familial, or idiopathic chronic pancreatitis (PMID:12644782)
• plasma leptin levels, rather than nonesterified fatty acids and tumor necrosis factor receptor 1, may play a significant role in the development of hyperinsulinemia and insulin resistance in children (PMID:12690082)
• TNFR1 apoptotic function is regulated by SODD/BAG4 (PMID:12706861)
• type 1 tumor necrosis factor receptor shedding aminopeptidase regulator(ARTS-1) promotes shedding of two cytokine receptor superfamilies, type I cytokine receptor superfamily (interleukin-6Ralpha) and tumor necrosis factor receptor superfamily (TNFR1) (PMID:12748171)
• HCMV infection of fully permissive differentiated monocytic cell lines and U373 cells resulted in a reduction in cell surface expression of TNFRI and thus inhibition of TNFalpha signaling (PMID:12768019)
• TNFR1 stimulates cytosolic phospholipase A2 (cPLA2) with distinct signaling mechanisms, by activating mitogen-activated protein kinase (MAPK) and p38MAPK, then phosphorylating and activating cPLA2 in a MAPK-dependent fashion. (PMID:12786601)
• During leukocyte differentiation, time windows exist during which autocrine TNFalpha is active and then down-regulated by TNF receptor I, which may temper continuous up-regulation of synthesis of proteins involved in pericellular proteolysis. (PMID:12811828)
• (-308) TNF-alpha gene polymorphism may contribute to CHD risk in patients with type 2 diabetes and can be useful predictive marker for the diagnosis of CHD in type 2 diabetic women. (PMID:12818408)
• Missense mutations found in these genes are probably responsible for an improvement in function. (PMID:12832748)
• Neither the +36 TNFRSF1A SNP nor the +196 TNFRSF1B SNP is associated with RA severity in a population of Caucasian patients with RA. (PMID:12858434)
• High levels of the soluble, 55-kilodalton isoform of tumor necrosis factor receptor in bone marrow are correlated with the clinical outcome of children with acute lymphoblastic leukemia in first recurrence (PMID:12879482)
• TNFR1 signals both cell survival and apoptosis. (PMID:12887914)
• TNFR1-induced apoptosis involves two sequential signaling complexes. (PMID:12887920)
• preferential induction of prodestructive and proinflammatory mediators in rheumatoid arthritis synovial fibroblasts by the TNF-R55 (PMID:12913922)
• genetic basis among patients with “TRAPS-like” features is heterogeneous and TNFRSF1A mutations are not commonly associated with nonfamilial recurrent fevers of unknown etiology. (PMID:13130484)
• Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) is a dominantly inherited disorder characterised by recurrent episodes of sustained fever.Here we report a case of TRAPS with a novel TNFRSF1A mutation, C70S, in a Japanese family. (PMID:14610673)
• Epstein-Barr virus (EBV) immediate-early protein BZLF1 prevents TNF-alpha activation of target genes and TNF-alpha-induced cell death by down regulating TNF-R1 (PMID:14671137)
• carriers of the 92Q allele may be at increased risk of atherosclerosis (PMID:14694358)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tnfrsf1a	ENSDARG00000018569
danio_rerio	fas	ENSDARG00000043586
danio_rerio	si:ch211-112c15.8	ENSDARG00000089868
mus_musculus	Tnfrsf1a	ENSMUSG00000030341
rattus_norvegicus	Tnfrsf1a	ENSRNOG00000031312

Paralogs (21): FAS (ENSG00000026103), TNFRSF1B (ENSG00000028137), TNFRSF9 (ENSG00000049249), RELT (ENSG00000054967), NGFR (ENSG00000064300), 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 1A — P19438 (reviewed: P19438)

Alternative names: Tumor necrosis factor receptor 1, Tumor necrosis factor receptor type I, p55, p60

All UniProt accessions (9): P19438, A0A8V8TLL5, F5GWJ4, F5H061, F5H4T5, F5H6V7, F5H6Z2, F5H7N1, F5H8A6

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for TNFSF2/TNF and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.

Subunit / interactions. Binding of TNF to the extracellular domain leads to homotrimerization. The aggregated death domains provide a novel molecular interface that interacts specifically with the death domain of TRADD. Various TRADD-interacting proteins such as TRAFS, RIPK1 and possibly FADD, are recruited to the complex by their association with TRADD. This complex activates at least two distinct signaling cascades, apoptosis and NF-kappa-B signaling. Interacts with BAG4, BABAM2, FEM1B, GRB2, SQSTM1 and TRPC4AP. Interacts directly with NOL3 (via CARD domain); inhibits TNF-signaling pathway. Interacts with SH3RF2, TRADD and RIPK1. SH3RF2 facilitates the recruitment of RIPK1 and TRADD to TNFRSF1A in a TNF-dependent process. Interacts with PGLYRP1; this interaction is important for cell death induction. Interacts (via death domain) with MADD (via death domain). (Microbial infection) Interacts with mumps virus protein SH; this interaction inhibits downstream NF-kappa-B pathway activation. (Microbial infection) Interacts with HCV core protein. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL138. (Microbial infection) Interacts with host TNFRSF1A; this interaction leads to the stimulation of both surface expression and shedding of TNFRSF1A.

Subcellular location. Cell membrane. Golgi apparatus membrane. Secreted Secreted.

Post-translational modifications. The soluble form is produced from the membrane form by proteolytic processing. (Microbial infection) Glycosylated at Arg-376 by enteropathogenic E.coli protein NleB1 and S.typhimurium protein Ssek3: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions.

Disease relevance. Periodic fever, familial, autosomal dominant (FPF) [MIM:142680] A hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases. The disease is caused by variants affecting the gene represented in this entry. Multiple sclerosis 5 (MS5) [MIM:614810] A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheath, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Disease susceptibility is associated with variants affecting the gene represented in this entry. An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.

Domain organisation. The domain that induces A-SMASE is probably identical to the death domain. The N-SMASE activation domain (NSD) is both necessary and sufficient for activation of N-SMASE. Both the cytoplasmic membrane-proximal region and the C-terminal region containing the death domain are involved in the interaction with TRPC4AP.

Miscellaneous. Disease-associated isoform. Isoform 4 splicing pattern is driven by a variation in the exon 6/intron 6 boundary region that alters exon 6 splicing. Exon 6 skipping introduces a frameshift and the translation of a protein lacking the intracellular, the transmembrane and part of the extracellular domain.

Isoforms (5)

UniProt ID	Names	Canonical?
P19438-1	1, FL-TNFR1	yes
P19438-2	2
P19438-4	4, Delta6-TNFR1
P19438-3	3
P19438-5	5

RefSeq proteins (3): NP_001056, NP_001333020, NP_001333021 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000488	Death_dom	Domain
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR020419	TNFR_1A	Family
IPR033993	TNFRSF1A_N	Domain
IPR033994	TNFRSF1A_death	Domain
IPR052493	TNFRSF1A	Family

Pfam: PF00020, PF00531

UniProt features (83 total): strand 17, sequence variant 15, disulfide bond 12, helix 10, sequence conflict 6, splice variant 5, glycosylation site 4, repeat 4, chain 2, region of interest 2, topological domain 2, signal peptide 1, domain 1, transmembrane region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
8P6Q	X-RAY DIFFRACTION	1.4
1EXT	X-RAY DIFFRACTION	1.85
1NCF	X-RAY DIFFRACTION	2.25
8ZUI	ELECTRON MICROSCOPY	2.56
9V9C	ELECTRON MICROSCOPY	2.62
7KP7	X-RAY DIFFRACTION	2.65
1TNR	X-RAY DIFFRACTION	2.85
1FT4	X-RAY DIFFRACTION	2.9
7KPB	X-RAY DIFFRACTION	3
7KP8	X-RAY DIFFRACTION	3.15
9VIN	ELECTRON MICROSCOPY	3.41
1ICH	SOLUTION NMR
7K7A	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19438-F1	72.15	0.40

Antibody-complex structures (SAbDab): 1 — 7KPB

Functional residue map

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

Disulfide bonds (12): 44–58, 59–72, 62–81, 84–99, 102–117, 105–125, 127–143, 146–158, 149–166, 168–179, 182–195, 185–191

Glycosylation sites (4): 54, 145, 151, 376

Mutagenesis-validated functional residues (1):

Position	Phenotype
376	abolished glcnacylation by e.coli nleb1.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-5357786	TNFR1-induced proapoptotic signaling
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway
R-HSA-5626978	TNFR1-mediated ceramide production
R-HSA-5669034	TNFs bind their physiological receptors
R-HSA-6783783	Interleukin-10 signaling
R-HSA-75893	TNF signaling

MSigDB gene sets: 600 (showing top): PID_HDAC_CLASSI_PATHWAY, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, BIOCARTA_RELA_PATHWAY, GOBP_EPITHELIUM_DEVELOPMENT, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_ACTIVATION_OF_NF_KAPPAB_INDUCING_KINASE_ACTIVITY

GO Biological Process (39): protein polyubiquitination (GO:0000209), aortic valve development (GO:0003176), pulmonary valve development (GO:0003177), negative regulation of extracellular matrix constituent secretion (GO:0003332), transcription by RNA polymerase II (GO:0006366), prostaglandin metabolic process (GO:0006693), inflammatory response (GO:0006954), canonical NF-kappaB signal transduction (GO:0007249), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), negative regulation of cardiac muscle hypertrophy (GO:0010614), regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803), cytokine-mediated signaling pathway (GO:0019221), tumor necrosis factor-mediated signaling pathway (GO:0033209), obsolete positive regulation of amide metabolic process (GO:0034250), defense response to bacterium (GO:0042742), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), positive regulation of lipid metabolic process (GO:0045834), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of inflammatory response (GO:0050728), positive regulation of inflammatory response (GO:0050729), cellular response to mechanical stimulus (GO:0071260), protein localization to plasma membrane (GO:0072659), positive regulation of execution phase of apoptosis (GO:1900119), positive regulation of apoptotic process involved in morphogenesis (GO:1902339), regulation of establishment of endothelial barrier (GO:1903140), obsolete regulation of membrane lipid metabolic process (GO:1905038), apoptotic process (GO:0006915), defense response (GO:0006952), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), regulation of gene expression (GO:0010468), positive regulation of macromolecule biosynthetic process (GO:0010557), non-canonical NF-kappaB signal transduction (GO:0038061), regulation of developmental process (GO:0050793), regulation of multicellular organismal process (GO:0051239), apoptotic signaling pathway (GO:0097190)

GO Molecular Function (4): tumor necrosis factor receptor activity (GO:0005031), signaling receptor activity (GO:0038023), tumor necrosis factor binding (GO:0043120), protein binding (GO:0005515)

GO Cellular Component (10): Golgi membrane (GO:0000139), tumor necrosis factor receptor superfamily complex (GO:0002947), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), signaling receptor complex (GO:0043235), membrane raft (GO:0045121), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
TNF signaling	4
TNFR2 non-canonical NF-kB pathway	1
Signaling by Interleukins	1
Death Receptor Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
semi-lunar valve development	2
defense response	2
tumor necrosis factor-mediated signaling pathway	2
canonical NF-kappaB signal transduction	2
regulation of canonical NF-kappaB signal transduction	2
protein ubiquitination	1
regulation of extracellular matrix constituent secretion	1
extracellular matrix constituent secretion	1
negative regulation of extracellular matrix organization	1
negative regulation of secretion by cell	1
DNA-templated transcription	1
prostanoid metabolic process	1
intracellular signaling cassette	1
cell surface receptor signaling pathway via STAT	1
extrinsic apoptotic signaling pathway	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
negative regulation of muscle hypertrophy	1
regulation of cytokine-mediated signaling pathway	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
response to bacterium	1
positive regulation of intracellular signal transduction	1
negative regulation of intracellular signal transduction	1
lipid metabolic process	1
positive regulation of metabolic process	1
regulation of lipid metabolic process	1
death receptor activity	1
tumor necrosis factor binding	1
molecular transducer activity	1
cytokine binding	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
signaling receptor complex	1

Protein interactions and networks

STRING

3850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFRSF1A	TNF	P01375	999
TNFRSF1A	TRADD	Q15628	999
TNFRSF1A	FADD	Q13158	998
TNFRSF1A	IL1B	P01584	997
TNFRSF1A	IL6	P05231	997
TNFRSF1A	FASLG	P48023	997
TNFRSF1A	RIPK1	Q13546	997
TNFRSF1A	CASP8	Q14790	997
TNFRSF1A	LTA	P01374	996
TNFRSF1A	BIRC2	Q13490	995
TNFRSF1A	FAS	P25445	994
TNFRSF1A	TNFSF10	P50591	993
TNFRSF1A	TRAF2	Q12933	992
TNFRSF1A	TRAF5	O00463	991
TNFRSF1A	TNFRSF1B	P20333	988

IntAct

184 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
TNF	TNFRSF1A	psi-mi:“MI:0914”(association)	0.960
TNFRSF1A	TRADD	psi-mi:“MI:0915”(physical association)	0.960
TNFRSF1A	TRADD	psi-mi:“MI:0914”(association)	0.960
TRADD	TNFRSF1A	psi-mi:“MI:0915”(physical association)	0.960
TNF	TNFRSF1A	psi-mi:“MI:0915”(physical association)	0.960
TNFRSF1A	TNF	psi-mi:“MI:0407”(direct interaction)	0.960
TNFRSF1A	TNF	psi-mi:“MI:0915”(physical association)	0.960
TNF	TNFRSF1A	psi-mi:“MI:0407”(direct interaction)	0.960
TNFRSF1A	TNF	psi-mi:“MI:2364”(proximity)	0.960

BioGRID (489): RIPK1 (Affinity Capture-Western), RIPK1 (Affinity Capture-Western), TNFRSF1A (Two-hybrid), TNFRSF1A (Reconstituted Complex), TNFRSF1A (Biochemical Activity), TNFRSF1A (Affinity Capture-MS), NSMAF (Affinity Capture-Western), BIRC2 (Affinity Capture-Western), RIPK1 (Affinity Capture-Western), TRADD (Affinity Capture-Western), TNFRSF1A (Affinity Capture-MS), TNFRSF1A (Affinity Capture-MS), TNFRSF1A (Affinity Capture-MS), TNFRSF1A (Affinity Capture-MS), TNF (Co-localization)

ESM2 similar proteins: A0JNA2, A2RRU4, A4FUY1, A5D7V5, A8MVS5, D4A6L0, E1BBQ2, O19131, O54693, O75144, P09564, P15151, P19438, P29590, P31994, P32506, P32507, P50555, P97260, Q14CZ8, Q28110, Q3TEW6, Q53EL9, Q5BJT4, Q5DRQ8, Q5T848, Q61190, Q640R3, Q6AYP5, Q6AYT8, Q6BAA4, Q6GQT6, Q6P6J9, Q6UX15, Q70EL4, Q75VT8, Q7TSK2, Q7Z692, Q8C419, Q8N126

Diamond homologs: O00220, O14763, O14798, O19131, P15725, P19438, P47741, P50555, P83626, Q80WM9, Q9QZM4, Q9UBN6, O73559, P0DSV7, P0DSV8, P0DTN0, P22934, P25118, P25943, P68636, P68637, Q80WY6, Q92956, Q9ER62, Q9ER63, O00300, O08712, O08727, O35305, O95407, P20333, P21071, P21106, P24756, P25119, P25942, P27512, P29825, Q28203, Q3LRP1

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
TNF	“up-regulates activity”	TNFRSF1A	binding
TNFRSF1A	“up-regulates activity”	TRADD	binding
GRN	down-regulates	TNFRSF1A	binding
TNFRSF1A	up-regulates	MAPK14
KRT14	“down-regulates activity”	TNFRSF1A	binding
TNFRSF1A	up-regulates	TRAF2
TNFRSF1A	“down-regulates quantity by destabilization”	NFKBIA
BAG4	“down-regulates activity”	TNFRSF1A	binding
MAPK1	“down-regulates activity”	TNFRSF1A	phosphorylation
TNFRSF1A	“up-regulates activity”	MAPK14

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 135 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of NF-kappa B signaling	8	45.3×	7e-10
MAP3K8 (TPL2)-dependent MAPK1/3 activation	7	44.6×	9e-09
TICAM1, RIP1-mediated IKK complex recruitment	8	42.9×	9e-10
Caspase activation via Death Receptors in the presence of ligand	6	40.8×	2e-07
TNFR1-induced NF-kappa-B signaling pathway	12	36.0×	1e-13
IKK complex recruitment mediated by RIP1	8	35.5×	5e-09
Regulation of necroptotic cell death	9	35.3×	6e-10
RIPK1-mediated regulated necrosis	8	32.6×	8e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein refolding	6	30.0×	1e-05
canonical NF-kappaB signal transduction	8	23.4×	1e-06
tumor necrosis factor-mediated signaling pathway	8	21.1×	2e-06
positive regulation of extrinsic apoptotic signaling pathway	5	18.2×	6e-04
extrinsic apoptotic signaling pathway via death domain receptors	5	16.1×	1e-03
negative regulation of canonical NF-kappaB signal transduction	11	15.1×	2e-07
extrinsic apoptotic signaling pathway	6	14.7×	4e-04
platelet aggregation	5	13.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	16
Uncertain significance	248
Likely benign	203
Benign	39

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
12335	NM_001065.4(TNFRSF1A):c.185G>A (p.Cys62Tyr)	Pathogenic
12336	NM_001065.4(TNFRSF1A):c.236C>T (p.Thr79Met)	Pathogenic
12337	NM_001065.4(TNFRSF1A):c.175T>C (p.Cys59Arg)	Pathogenic
12338	NM_001065.4(TNFRSF1A):c.242G>T (p.Cys81Phe)	Pathogenic
12339	NM_001065.4(TNFRSF1A):c.349T>C (p.Cys117Arg)	Pathogenic
12340	NM_001065.4(TNFRSF1A):c.350G>A (p.Cys117Tyr)	Pathogenic
12344	TNFRSF1A, 3-BP DEL, NT211	Pathogenic
12345	NM_001065.4(TNFRSF1A):c.295T>A (p.Cys99Ser)	Pathogenic
12346	C55A	Pathogenic
267318	NM_001065.3(TNFRSF1A):c.463C>T (p.His155Tyr)	Pathogenic
800355	NM_001065.4(TNFRSF1A):c.362_363insTGCAAGACACAG (p.Arg121_Asp122insAlaArgHisArg)	Pathogenic
97646	NM_001065.4(TNFRSF1A):c.151C>T (p.His51Tyr)	Pathogenic
97651	NM_001065.4(TNFRSF1A):c.173G>T (p.Cys58Phe)	Pathogenic
97673	NM_001065.4(TNFRSF1A):c.251G>A (p.Cys84Tyr)	Pathogenic
97690	NM_001065.4(TNFRSF1A):c.306C>G (p.Cys102Trp)	Pathogenic
12343	NM_001065.4(TNFRSF1A):c.184T>G (p.Cys62Gly)	Likely pathogenic
1469585	NM_001065.4(TNFRSF1A):c.305G>T (p.Cys102Phe)	Likely pathogenic
1509170	NM_001065.4(TNFRSF1A):c.172T>G (p.Cys58Gly)	Likely pathogenic
1694196	NM_001065.4(TNFRSF1A):c.215G>T (p.Cys72Phe)	Likely pathogenic
1917928	NM_001065.4(TNFRSF1A):c.349T>G (p.Cys117Gly)	Likely pathogenic
234460	NM_001065.4(TNFRSF1A):c.317G>A (p.Arg106Gln)	Likely pathogenic
2682154	NM_001065.4(TNFRSF1A):c.950_951insTG (p.Tyr318fs)	Likely pathogenic
431949	NM_001065.4(TNFRSF1A):c.305G>C (p.Cys102Ser)	Likely pathogenic
4539317	NM_001065.4(TNFRSF1A):c.472+2T>C	Likely pathogenic
97663	NM_001065.4(TNFRSF1A):c.214T>C (p.Cys72Arg)	Likely pathogenic
97664	NM_001065.4(TNFRSF1A):c.215G>A (p.Cys72Tyr)	Likely pathogenic
97668	NM_001065.4(TNFRSF1A):c.241T>C (p.Cys81Arg)	Likely pathogenic
97672	NM_001065.4(TNFRSF1A):c.250T>C (p.Cys84Arg)	Likely pathogenic
97694	NM_001065.4(TNFRSF1A):c.361C>T (p.Arg121Trp)	Likely pathogenic
97698	NM_001065.4(TNFRSF1A):c.380G>A (p.Cys127Tyr)	Likely pathogenic

SpliceAI

1481 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6329618:ATCAG:A	acceptor_gain	1.0000
12:6329619:TCAG:T	acceptor_gain	1.0000
12:6329620:CAG:C	acceptor_gain	1.0000
12:6329620:CAGC:C	acceptor_gain	1.0000
12:6329621:AG:A	acceptor_gain	1.0000
12:6329622:GCTGC:G	acceptor_loss	1.0000
12:6329623:C:CC	acceptor_gain	1.0000
12:6329623:CTGC:C	acceptor_loss	1.0000
12:6329624:T:A	acceptor_loss	1.0000
12:6329776:A:AC	donor_gain	1.0000
12:6329777:C:CT	donor_gain	1.0000
12:6329777:CTGT:C	donor_gain	1.0000
12:6330062:TCCCC:T	acceptor_gain	1.0000
12:6330063:CCCC:C	acceptor_gain	1.0000
12:6330063:CCCCC:C	acceptor_gain	1.0000
12:6330064:CCCC:C	acceptor_gain	1.0000
12:6330065:CC:C	acceptor_gain	1.0000
12:6330066:CC:C	acceptor_gain	1.0000
12:6330067:C:CA	acceptor_loss	1.0000
12:6330067:C:CC	acceptor_gain	1.0000
12:6330292:CAAA:C	acceptor_gain	1.0000
12:6330296:C:CC	acceptor_gain	1.0000
12:6330594:TCACC:T	donor_loss	1.0000
12:6330595:CA:C	donor_loss	1.0000
12:6330596:A:AC	donor_gain	1.0000
12:6330596:ACC:A	donor_loss	1.0000
12:6330597:C:CA	donor_loss	1.0000
12:6330597:C:CC	donor_gain	1.0000
12:6330597:CCA:C	donor_gain	1.0000
12:6330712:C:CC	acceptor_gain	1.0000

AlphaMissense

2957 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6333792:G:C	F89L	0.998
12:6333792:G:T	F89L	0.998
12:6333794:A:G	F89L	0.998
12:6334099:C:G	C62S	0.998
12:6334100:A:T	C62S	0.998
12:6329391:A:G	L430P	0.997
12:6329461:A:G	W407R	0.997
12:6329461:A:T	W407R	0.997
12:6329559:A:G	F374S	0.997
12:6329569:A:G	W371R	0.997
12:6329569:A:T	W371R	0.997
12:6333808:C:G	C84S	0.997
12:6333809:A:T	C84S	0.997
12:6334100:A:G	C62R	0.997
12:6333411:C:G	C143S	0.996
12:6333412:A:T	C143S	0.996
12:6333459:C:G	C127S	0.996
12:6333460:A:T	C127S	0.996
12:6333745:C:G	C105S	0.996
12:6333746:A:T	C105S	0.996
12:6333763:C:G	C99S	0.996
12:6333764:A:T	C99S	0.996
12:6333817:C:G	C81S	0.996
12:6333818:A:T	C81S	0.996
12:6334098:G:C	C62W	0.996
12:6329459:C:A	W407C	0.995
12:6329459:C:G	W407C	0.995
12:6329567:C:A	W371C	0.995
12:6329567:C:G	W371C	0.995
12:6333417:A:C	F141C	0.995

dbSNP variants (sampled 300 via entrez): RS1000087625 (12:6335607 AT>A,ATT), RS1001104136 (12:6328436 C>A,T), RS1001332411 (12:6335776 G>A), RS1001385706 (12:6335474 C>G,T), RS1001594689 (12:6341491 T>A,C), RS1001674121 (12:6328906 A>G), RS1001773835 (12:6336277 C>CT), RS1001866570 (12:6340410 G>A), RS1001957616 (12:6341030 G>C,T), RS1002321942 (12:6340095 A>G), RS1002542038 (12:6343161 C>T), RS1002916372 (12:6343512 C>G), RS1003531230 (12:6331258 C>T), RS1003662238 (12:6337593 C>T), RS1003755773 (12:6337815 G>A)

Disease associations

OMIM: gene MIM:191190 | disease phenotypes: MIM:142680, MIM:614810, MIM:109650

GenCC curated gene-disease

Disease	Classification	Inheritance
TNF receptor 1-associated periodic fever syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
TNF receptor 1-associated periodic fever syndrome	Definitive	AD

Mondo (6): TNF receptor 1-associated periodic fever syndrome (MONDO:0007727), autoinflammatory syndrome (MONDO:0019751), multiple sclerosis (MONDO:0005301), multiple sclerosis, susceptibility to, 5 (MONDO:0013893), Behcet disease (MONDO:0007191), CHARGE syndrome (MONDO:0008965)

Orphanet (5): Tumor necrosis factor receptor 1 associated periodic syndrome (Orphanet:32960), Autoinflammatory syndrome (Orphanet:93665), Behçet disease (Orphanet:117), CHARGE syndrome (Orphanet:138), NON RARE IN EUROPE: Multiple sclerosis (Orphanet:802)

HPO phenotypes

59 total (30 of 59 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000509	Conjunctivitis
HP:0000554	Uveitis
HP:0000708	Atypical behavior
HP:0000934	Chondrocalcinosis
HP:0000978	Bruising susceptibility
HP:0000988	Skin rash
HP:0001034	Hypermelanotic macule
HP:0001055	Erysipelas
HP:0001369	Arthritis
HP:0001386	Joint swelling
HP:0001637	Abnormal myocardium morphology
HP:0001701	Pericarditis
HP:0001744	Splenomegaly
HP:0001954	Recurrent fever
HP:0001974	Increased total leukocyte count
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002028	Chronic diarrhea
HP:0002076	Migraine
HP:0002102	Pleuritis
HP:0002239	Gastrointestinal hemorrhage
HP:0002240	Hepatomegaly
HP:0002315	Headache
HP:0002321	Vertigo
HP:0002586	Peritonitis
HP:0002633	Vasculitis
HP:0002653	Bone pain

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST000424_15	Multiple sclerosis	2.000000e-11
GCST000424_6	Multiple sclerosis	5.000000e-06
GCST001010_6	Primary biliary cholangitis	2.000000e-09
GCST001198_38	Multiple sclerosis	4.000000e-14
GCST001996_2	Adverse response to chemotherapy (neutropenia/leucopenia) (epirubicin)	3.000000e-07
GCST002008_2	Adverse response to chemotherapy (neutropenia/leucopenia) (all anthracycline-based drugs)	7.000000e-06
GCST002454_10	Colorectal cancer	6.000000e-10
GCST003044_41	Crohn’s disease	1.000000e-09
GCST003129_16	Primary biliary cholangitis	2.000000e-09
GCST003566_15	Multiple sclerosis	3.000000e-08
GCST004302_10	Primary biliary cholangitis	4.000000e-09
GCST004603_102	Platelet count	5.000000e-09
GCST004607_40	Plateletcrit	2.000000e-16
GCST004625_118	Monocyte count	1.000000e-16
GCST004627_23	Lymphocyte count	1.000000e-09
GCST004866_8	Alopecia areata	8.000000e-06
GCST005529_23	Ankylosing spondylitis	8.000000e-10
GCST005529_30	Ankylosing spondylitis	1.000000e-07
GCST005529_41	Ankylosing spondylitis	3.000000e-10
GCST005531_55	Multiple sclerosis	7.000000e-28
GCST005537_85	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	3.000000e-17
GCST005581_33	Primary biliary cirrhosis	2.000000e-16
GCST005581_34	Primary biliary cirrhosis	7.000000e-19
GCST005581_7	Primary biliary cirrhosis	1.000000e-14
GCST005581_8	Primary biliary cirrhosis	2.000000e-09
GCST009597_147	Multiple sclerosis	2.000000e-47
GCST009597_296	Multiple sclerosis	4.000000e-10
GCST90002381_534	Eosinophil count	5.000000e-15
GCST90002388_416	Lymphocyte count	3.000000e-33
GCST90002389_378	Lymphocyte percentage of white cells	3.000000e-11

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0005257	response to anthracycline-based chemotherapy
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0004842	eosinophil count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D001528	Behcet Syndrome	C07.465.075; C11.941.879.780.880.200; C14.907.940.100; C16.320.382.250; C17.800.827.368.250; C17.800.862.150
D058747	CHARGE Syndrome	C09.218.458.341.186.500.250; C10.597.751.418.341.186.500.250; C10.597.751.941.162.625.250; C11.270.147.500; C11.966.075.375.250; C16.131.077.299.250; C16.320.165; C23.888.592.763.393.341.186.500.500; C23.888.592.763.941.162.625.500
D009103	Multiple Sclerosis	C10.114.375.500; C10.314.350.500; C20.111.258.250.500
C536657	Periodic fever, familial, autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3378 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 721 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL36584	METOCHALCONE	2	721

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4149570	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Crohn Disease;Inflammatory Bowel Diseases
rs767455	Efficacy	3	adalimumab;etanercept;infliximab	Arthritis;Psoriatic
rs767455	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Rheumatoid arthritis

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs767455	TNFRSF1A	3	2.75	2	adalimumab;etanercept;infliximab;Tumor necrosis factor alpha (TNF-alpha) inhibitors
rs1800693	TNFRSF1A		0.00	0
rs4149570	TNFRSF1A	3	3.50	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors
rs2234649	TNFRSF1A		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

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

ChEMBL bioactivities

101 potent at pChembl≥5 of 120 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	Kd	0.1	nM	CHEMBL6168974
9.85	Kd	0.14	nM	CHEMBL6169727
9.70	IC50	0.2	nM	CHEMBL6168974
9.70	Kd	0.2	nM	CHEMBL6148370
9.26	IC50	0.55	nM	CHEMBL6148370
9.22	IC50	0.6	nM	CHEMBL6169727
6.89	IC50	130	nM	CHEMBL359346
6.85	IC50	140	nM	CHEMBL357092
6.68	IC50	210	nM	CHEMBL150292
6.68	IC50	210	nM	CHEMBL356012
6.55	IC50	280	nM	CHEMBL356830
6.55	IC50	280	nM	CHEMBL151203
6.52	IC50	300	nM	CHEMBL150886
6.51	IC50	310	nM	CHEMBL423208
6.50	IC50	320	nM	CHEMBL146955
6.41	IC50	390	nM	CHEMBL151686
6.40	IC50	400	nM	CHEMBL150992
6.22	IC50	600	nM	CHEMBL359348
6.21	IC50	610	nM	CHEMBL345772
6.17	IC50	670	nM	CHEMBL355913
6.11	IC50	770	nM	CHEMBL4213787
6.11	IC50	780	nM	CHEMBL151752
6.10	IC50	790	nM	CHEMBL347715
6.00	Kd	996.1	nM	CHEMBL5414162
6.00	IC50	1000	nM	CHEMBL39798
6.00	IC50	1000	nM	CHEMBL37662
6.00	IC50	1000	nM	CHEMBL39656
6.00	IC50	1000	nM	CHEMBL39896
6.00	IC50	1000	nM	CHEMBL37663
6.00	IC50	1000	nM	CHEMBL289427
6.00	IC50	1000	nM	CHEMBL290167
6.00	IC50	1000	nM	CHEMBL263418
6.00	IC50	1000	nM	CHEMBL345500
6.00	IC50	1000	nM	CHEMBL151578
5.96	IC50	1100	nM	CHEMBL345771
5.77	IC50	1700	nM	CHEMBL150870
5.75	IC50	1800	nM	CHEMBL147036
5.72	IC50	1900	nM	CHEMBL149958
5.70	IC50	2000	nM	CHEMBL465465
5.70	IC50	2000	nM	CHEMBL37200
5.70	IC50	2000	nM	CHEMBL449083
5.70	IC50	2000	nM	CHEMBL290392
5.70	IC50	2000	nM	CHEMBL36371
5.70	IC50	2000	nM	CHEMBL435172
5.70	IC50	2000	nM	CHEMBL40731
5.70	IC50	2000	nM	CHEMBL405035
5.70	IC50	2000	nM	CHEMBL285544
5.70	IC50	2000	nM	CHEMBL39400
5.70	IC50	2000	nM	CHEMBL37382
5.70	IC50	2000	nM	CHEMBL38312

PubChem BioAssay actives

95 with measured affinity, of 162 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1,3-diethyl-5-[(1-methylindol-3-yl)methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.1300	uM
(5Z)-3-ethyl-5-[[5-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl]thiophen-2-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.1400	uM
5,7-dimethoxy-4-methyl-2-prop-2-enylimidazo[1,5-a]indole-1,3-dithione	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.2100	uM
5,7-dimethoxy-4-methyl-2-prop-2-enyl-3-sulfanylideneimidazo[1,5-a]indol-1-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.2100	uM
2-ethyl-5-methoxy-7-(methoxymethoxy)-1-sulfanylideneimidazo[1,5-a]indol-3-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.2800	uM
5,7-dimethoxy-2-prop-2-enyl-1-sulfanylideneimidazo[1,5-a]indol-3-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.2800	uM
methyl 3-[5-[(Z)-(3-ethyl-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]furan-2-yl]thiophene-2-carboxylate	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.3000	uM
2-ethyl-5-methoxy-7-(pyridin-2-ylmethoxy)-1-sulfanylideneimidazo[1,5-a]indol-3-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.3100	uM
(5Z)-3-ethyl-2-sulfanylidene-5-[[5-[2-(trifluoromethyl)phenyl]furan-2-yl]methylidene]-1,3-thiazolidin-4-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.3200	uM
tert-butyl 2-(2-ethyl-5-methoxy-3-oxo-1-sulfanylideneimidazo[1,5-a]indol-7-yl)oxyacetate	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.3900	uM
1,3-diethyl-6-hydroxy-5-[(Z)-(5-phenylmethoxyindol-3-ylidene)methyl]-2-sulfanylidenepyrimidin-4-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.4000	uM
1,3-diethyl-6-hydroxy-5-[(Z)-(7-methylindol-3-ylidene)methyl]-2-sulfanylidenepyrimidin-4-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.6000	uM
5,7-dimethoxy-2-prop-2-enyl-3-sulfanylideneimidazo[1,5-a]indol-1-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.6100	uM
5,7-dimethoxy-2-(3-morpholin-4-ylpropyl)-1-sulfanylideneimidazo[1,5-a]indol-3-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.6700	uM
2-(2,4-dichlorophenyl)-N’-(pyridine-2-carbonyl)-1,3-thiazole-4-carbohydrazide	1381056: Inhibition of TNFR in TLR null HEK-blue cells assessed as decrease in TNFalpha-stimulated NF-kappaB activation-mediated SEAP production after 24 hrs by Quanti-blue-based assay	ic50	0.7700	uM
5,6,7-trimethoxy-2-prop-2-enyl-1-sulfanylideneimidazo[1,5-a]indol-3-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.7800	uM
6-hydroxy-5-[(Z)-indol-3-ylidenemethyl]-1,3-bis(2-methylphenyl)-2-sulfanylidenepyrimidin-4-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	0.7900	uM
(2S)-2-[[(2S,3R)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-aminopropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1989566: Inhibition of TNF-alpha (unknown origin) binding to TNFR1 assessed as dissociation constant of TNF-alpha preincubated for 15 mins by MST assay (Rvb = 13.4 nM)	kd	0.9961	uM
(E)-1-[3,5-dimethoxy-4-[(4-methoxyphenyl)methoxy]phenyl]-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	1.0000	uM
1,3-diethyl-6-hydroxy-5-[(Z)-indol-3-ylidenemethyl]-2-sulfanylidenepyrimidin-4-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	1.0000	uM
2-[4-[(E)-3-[5-(1-benzothiophen-2-yl)-2,4-dimethoxyphenyl]prop-2-enoyl]phenyl]sulfanylacetic acid	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	1.0000	uM
(E)-3-[5-(1-benzothiophen-2-yl)-2,4-dimethoxyphenyl]-1-(4-hydroxy-3,5-dimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	1.0000	uM
2-[4-(1-benzothiophen-2-yl)-5-methoxy-2-[(E)-3-oxo-3-phenylprop-1-enyl]phenoxy]acetic acid	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	1.0000	uM
2-[4-[(E)-3-(3,4-dimethoxy-5-thiophen-2-ylphenyl)prop-2-enoyl]-2,6-dimethoxyphenoxy]acetic acid	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	1.0000	uM
2-[2,6-dimethoxy-4-[(E)-3-(2-methoxy-5-thiophen-2-ylphenyl)prop-2-enoyl]phenoxy]acetic acid	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	1.0000	uM
(E)-1-(2,2-dihydroxy-1,3-benzodioxol-5-yl)-3-(3,4-dimethoxy-5-thiophen-2-ylphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	1.0000	uM
2-ethyl-5,7-dimethoxy-1-sulfanylideneimidazo[1,5-a]indol-3-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	1.0000	uM
(E)-3-(5-bromo-2-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	1.0000	uM
5,7-dimethoxy-4-methyl-2-prop-2-enyl-1-sulfanylideneimidazo[1,5-a]indol-3-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	1.1000	uM
7-methoxy-2-prop-2-enyl-1-sulfanylideneimidazo[1,5-a]indol-3-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	1.7000	uM
6-hydroxy-5-[(Z)-indol-3-ylidenemethyl]-1-(2-methylphenyl)-2-sulfanylidenepyrimidin-4-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	1.8000	uM
5,7-dimethoxy-2-(2-phenylethyl)-1-sulfanylideneimidazo[1,5-a]indol-3-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	1.9000	uM
(E)-3-(2,4-dimethoxy-5-thiophen-2-ylphenyl)-1-(2,3,4-trimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-1-(3,4-dimethoxyphenyl)-3-[2-methoxy-5-(4-methylthiophen-2-yl)phenyl]prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-1-(2,5-dimethoxyphenyl)-3-(2-methoxy-5-thiophen-2-ylphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-3-[5-(1-benzothiophen-2-yl)-2-methoxyphenyl]-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-3-(3,4-difluorophenyl)-1-(2-methoxy-4-thiophen-2-ylphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-3-[2-methoxy-5-(5-methylthiophen-2-yl)phenyl]-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-1-(3,4-dimethoxyphenyl)-3-[2-methoxy-5-(5-methylthiophen-2-yl)phenyl]prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-1-(3,5-dimethoxyphenyl)-3-(2-methoxy-5-thiophen-2-ylphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-3-[5-(1-benzothiophen-2-yl)-2-methoxyphenyl]-1-(3,4-dimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-3-[2-methoxy-5-(4-methylthiophen-2-yl)phenyl]-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-1-[4-[(3,4-dimethoxyphenyl)methoxy]-3,5-dimethoxyphenyl]-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-3-(3-bromo-4,5-dimethoxyphenyl)-1-(2,4,5-trimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-1-[3,5-dimethoxy-4-(3-methoxy-1,4-benzodioxin-2-yl)phenyl]-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-1-[4-[(3,4-dimethoxyphenyl)methoxy]-3-methoxyphenyl]-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
(E)-3-(5-bromo-2,4-dimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one	226858: Inhibition of TNF-alpha-induced VCAM-1 expression	ic50	2.0000	uM
1,3-diethyl-2-sulfanylidene-5-[[5-[2-(trifluoromethyl)phenyl]furan-2-yl]methylidene]-1,3-diazinane-4,6-dione	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	2.0000	uM
3,4-difluoro-2-(2-fluoro-4-iodoanilino)-5-[[(4-methylsulfonylphenyl)methylamino]methyl]benzoic acid	410441: Binding affinity to TRAK-A	ic50	2.0000	uM
5-methoxy-2-prop-2-enyl-1-sulfanylideneimidazo[1,5-a]indol-3-one	214895: Inhibition of TNF-alpha binding to TNFRc1	ic50	2.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases reaction, decreases expression, affects cotreatment, affects expression, increases expression	4
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	4
dioscin	increases expression	3
ochratoxin A	affects cotreatment, decreases expression	3
Arsenic Trioxide	affects cotreatment, increases expression	3
Cadmium	affects cotreatment, increases expression, decreases expression	3
Hydrogen Peroxide	decreases reaction, increases expression, increases cleavage, increases secretion	3
Plant Extracts	decreases reaction, increases expression	3
Selenium	increases expression, increases reaction, affects cotreatment, decreases reaction	3
Tobacco Smoke Pollution	increases reaction, decreases expression, decreases reaction, increases expression, increases secretion (+1 more)	3
Tretinoin	affects cotreatment, increases expression	3
moringin	affects cotreatment, decreases expression	2
methylmercuric chloride	increases expression	2
titanium dioxide	decreases expression	2
sodium arsenite	decreases expression, increases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	2
Resveratrol	decreases expression, decreases reaction, increases expression	2
Zoledronic Acid	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Acetylcysteine	decreases expression, decreases reaction, increases cleavage	2
Ethanol	increases expression, affects cotreatment, increases abundance	2
Cannabidiol	affects cotreatment, decreases expression, increases expression	2
Curcumin	decreases reaction, increases expression	2
Mustard Gas	affects reaction, increases secretion, affects expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, increases expression	2
Paraquat	decreases expression, increases expression	2
Smoke	decreases expression, increases expression	2
Tetradecanoylphorbol Acetate	increases expression, decreases expression, decreases reaction	2
Thalidomide	decreases expression	2
Valproic Acid	decreases expression, affects expression	2

ChEMBL screening assays

24 unique, capped per target: 23 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1250086	Binding	Binding affinity to human TNFR1 by surface plasmon resonance method	C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L. — Nat Chem Biol
CHEMBL845189	Functional	Inhibition of TNF-alpha-induced VCAM-1 expression	Discovery of novel heteroaryl-substituted chalcones as inhibitors of TNF-alpha-induced VCAM-1 expression. — Bioorg Med Chem Lett

Cellosaurus cell lines

22 cell lines: 15 transformed cell line, 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8CL	HEK-Blue IL-1beta	Transformed cell line	Female
CVCL_A8CM	HEK-Blue IL-1R	Transformed cell line	Female
CVCL_A8CQ	HEK-Blue-Lucia Null (NF/IL8)	Transformed cell line	Female
CVCL_A8CR	HEK-Blue-Lucia hTLR2 (NF/IL8)	Transformed cell line	Female
CVCL_A8CS	HEK-Blue-Lucia hTLR3 (NF/IL8)	Transformed cell line	Female
CVCL_A8CT	HEK-Blue-Lucia hTLR5 (NF/IL8)	Transformed cell line	Female
CVCL_A8CU	HEK-Blue-Lucia hTLR9 (NF/IL8)	Transformed cell line	Female
CVCL_A8CV	HEK-Blue-Lucia mTLR4 (NF/IL8)	Transformed cell line	Female
CVCL_A8CW	HEK-Blue-Lucia mTLR7 (NF/IL8)	Transformed cell line	Female
CVCL_B2J3	Abcam HeLa TNFRSF1A KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05857085	PHASE4	COMPLETED	Novel Therapeutics and Endothelial Dysfunction in T1DM Patients
NCT00037102	PHASE4	COMPLETED	Combination Therapy With Avonex and BiMonthly High Dose Intravenous Methotrexate in Multiple Sclerosis
NCT00037115	PHASE4	WITHDRAWN	Induction Therapy With a Single High Dose Bolus of Intravenous Methotrexate With Leucovorin Rescue, Prior to Initiation of AVONEX® Treatment, in Patients Presenting With a First Acute Demyelinating Event.
NCT00146068	PHASE4	COMPLETED	EARLY IFNB-1a and Simvastatin Combination Therapy in Clinically Isolated Syndrome Suggestive of Multiple Sclerosis
NCT00151294	PHASE4	TERMINATED	The Efficacy and Safety of Escitalopram for Depression in Multiple Sclerosis
NCT00176592	PHASE4	COMPLETED	Phase IV Study, Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI
NCT00179478	PHASE4	COMPLETED	Long Term Study of Avonex Therapy Following a First Attack of Multiple Sclerosis
NCT00220922	PHASE4	COMPLETED	A Study to Evaluate the Impact on Skin (Injection Site) Reactions of Using Alcohol Wipes Prior to Daily Injections of Copaxone®.
NCT00239993	PHASE4	COMPLETED	A Study to Evaluate the Impact of Using Warm Compress Prior to Daily Injections of Copaxone®
NCT00240006	PHASE4	COMPLETED	A Study Comparing Shared Solutions® Plus MS Center Support Versus Shared Solutions® Alone
NCT00240032	PHASE4	COMPLETED	A Study to Evaluate the Impact on Skin (Injection Site) Reactions of Taking an Antihistamine (Zyrtec®) or Placebo Prior to Daily Injections of Copaxone®.
NCT00246324	PHASE4	COMPLETED	Safety and Efficacy Study of Doxycycline in Combination With Interferon-B-1a to Treat Multiple Sclerosis
NCT00267319	PHASE4	COMPLETED	FOCUS Fatigue Outcome in Copaxone USers
NCT00381264	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Multiple Sclerosis
NCT00414453	PHASE4	TERMINATED	Trial of Analgesia With Lidocaine or Extended-release Oxycodone for Neuropathic Pain Treatment in Multiple Sclerosis
NCT00423527	PHASE4	COMPLETED	Levetiracetam in Central Pain in Multiple Sclerosis(MS)
NCT00480181	PHASE4	COMPLETED	Efficacy and Safety Evaluation of Nabilone as Adjunctive Therapy to Gabapentin for the Management of Neuropathic Pain in Multiple Sclerosis
NCT00492765	PHASE4	COMPLETED	Simvastatin as an Add-on Treatment to Interferon-beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis
NCT00493077	PHASE4	COMPLETED	Safety of Avonex Treatment in Multiple Sclerosis Patients With Neutralizing Antibodies to Interferon Beta Therapy
NCT00536120	PHASE4	COMPLETED	The Effects of Tysabri Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis
NCT00629642	PHASE4	COMPLETED	Clinical Study of Solifenacin Succinate in Patients With Bladder Symptoms Due to Spinal Cord Injury or Multiple Sclerosis
NCT00638027	PHASE4	COMPLETED	Memantine for Spasticity in MS Patients
NCT00744679	PHASE4	COMPLETED	A Pharmacokinetic (PK) Study of Natalizumab (Tysabri) at Steady State
NCT00752778	PHASE4	TERMINATED	Magnetic Resonance Imaging (MRI) Follow-up of Macrophagic Infiltration in MS Patients Treated With Tysabri
NCT00753792	PHASE4	COMPLETED	Oral Corticotherapy in Megadoses to Treat Multiple Sclerosis During Relapse
NCT00854750	PHASE4	TERMINATED	Modeling and Treating the Pathophysiology of Demyelination in Multiple Sclerosis
NCT00881205	PHASE4	TERMINATED	Rivastigmine in Multiple Sclerosis Patients With Cognitive Impairment
NCT00910598	PHASE4	UNKNOWN	Optical Coherence Tomography: Glatiramer in Clinically Isolated Syndrome or Early Relapsing Remitting Multiple Sclerosis (MS)
NCT00913666	PHASE4	COMPLETED	Pharmacodynamic Study to Better Understand the Therapeutic Response and Immunomodulatory Effects of Avonex in Multiple Sclerosis (MS) Patients and Healthy Volunteers
NCT00915460	PHASE4	COMPLETED	Open-Label Safety Extension Study of Avonex
NCT00942214	PHASE4	COMPLETED	Biomarkers and Response to Natalizumab for Multiple Sclerosis Treatment
NCT00988988	PHASE4	WITHDRAWN	The Effects of Ethyl-Alpha-Guanido-Methyl Ethanoate on Skin Reactions From Glatiramer Acetate Injections
NCT01005095	PHASE4	TERMINATED	The Effects of Interferon Beta Combined With Vitamin D on Relapsing Remitting Multiple Sclerosis Patients
NCT01034579	PHASE4	COMPLETED	The REbif® vs Glatiramer Acetate in Relapsing Multiple Sclerosis Pharmacogenetics Trial
NCT01085318	PHASE4	COMPLETED	Rebif Advanced Magnetic Resonance Imaging (MRI) and Immunology Pilot Trial
NCT01236534	PHASE4	COMPLETED	Lubiprostone in Patients With Multiple Sclerosis Associated Constipation
NCT01333501	PHASE4	COMPLETED	Fingolimod Versus Interferon Beta 1b in Cognitive Symptoms
NCT01339676	PHASE4	UNKNOWN	Colecalciferol as an Add-on Treatment to Interferon-beta-1b for Treatment of Multiple Sclerosis (MS)
NCT01356940	PHASE4	COMPLETED	A Placebo Controlled Trial of Dalfampridine ER for Ambulatory Activity in People With Multiple Sclerosis
NCT01395316	PHASE4	COMPLETED	Alemtuzumab on Surrogate Markers of Disease Activity and Repair Using Advanced MRI Measures in Subjects With Relapsing Remitting Multiple Sclerosis