TRAF1

Summary

TRAF1 (TNF receptor associated factor 1, HGNC:12031) is a protein-coding gene on chromosome 9q33.2, encoding TNF receptor-associated factor 1 (Q13077). Adapter molecule that regulates the activation of NF-kappa-B and JNK.

The protein encoded by this gene is a member of the TNF receptor (TNFR) associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from various receptors of the TNFR superfamily. This protein and TRAF2 form a heterodimeric complex, which is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF2 also interacts with inhibitor-of-apoptosis proteins (IAPs), and thus mediates the anti-apoptotic signals from TNF receptors. The expression of this protein can be induced by Epstein-Barr virus (EBV). EBV infection membrane protein 1 (LMP1) is found to interact with this and other TRAF proteins; this interaction is thought to link LMP1-mediated B lymphocyte transformation to the signal transduction from TNFR family receptors. Three transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 7185 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_005658

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12031
Approved symbol	TRAF1
Name	TNF receptor associated factor 1
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	EBI6
Ensembl gene	ENSG00000056558
Ensembl biotype	protein_coding
OMIM	601711
Entrez	7185

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000373887, ENST00000540010, ENST00000546084, ENST00000871615, ENST00000871616, ENST00000871617, ENST00000913542, ENST00000963770, ENST00000963771, ENST00000963772, ENST00000963773, ENST00000963774, ENST00000963775

RefSeq mRNA: 3 — MANE Select: NM_005658 NM_001190945, NM_001190947, NM_005658

CCDS: CCDS55335, CCDS6825

Canonical transcript exons

ENST00000373887 — 8 exons

Exon	Start	End
ENSE00000724273	120909230	120909378
ENSE00000724276	120911336	120911513
ENSE00000724283	120923705	120923792
ENSE00001276511	120926550	120926796
ENSE00001461844	120902393	120905238
ENSE00001461854	120925936	120926301
ENSE00003490173	120913328	120913738
ENSE00003586866	120914235	120914300

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 90.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.3587 / max 2449.6033, expressed in 1336 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102321	42.9253	842
102325	1.7138	300
102326	1.3105	616
102323	0.5704	84
102327	0.4172	221
102320	0.1768	58
102317	0.1132	59
102324	0.0689	33
102322	0.0626	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	90.73	gold quality
right coronary artery	UBERON:0001625	88.84	gold quality
descending thoracic aorta	UBERON:0002345	87.66	gold quality
ascending aorta	UBERON:0001496	86.76	gold quality
thoracic aorta	UBERON:0001515	86.73	gold quality
lymph node	UBERON:0000029	86.50	gold quality
aorta	UBERON:0000947	85.09	gold quality
popliteal artery	UBERON:0002250	84.12	gold quality
tibial artery	UBERON:0007610	84.11	gold quality
left coronary artery	UBERON:0001626	84.05	gold quality
vermiform appendix	UBERON:0001154	83.43	gold quality
coronary artery	UBERON:0001621	83.10	gold quality
tibial nerve	UBERON:0001323	82.69	gold quality
mucosa of stomach	UBERON:0001199	82.48	gold quality
blood	UBERON:0000178	81.20	gold quality
cartilage tissue	UBERON:0002418	80.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.86	gold quality
left adrenal gland cortex	UBERON:0035825	80.48	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.41	gold quality
lower esophagus	UBERON:0013473	80.36	gold quality
right adrenal gland	UBERON:0001233	80.22	gold quality
apex of heart	UBERON:0002098	80.14	gold quality
right ovary	UBERON:0002118	80.08	gold quality
right adrenal gland cortex	UBERON:0035827	79.98	gold quality
left ovary	UBERON:0002119	79.77	gold quality
left adrenal gland	UBERON:0001234	79.75	gold quality
spleen	UBERON:0002106	79.62	gold quality
pituitary gland	UBERON:0000007	79.28	gold quality
adenohypophysis	UBERON:0002196	79.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.83	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	26.40
E-MTAB-8498	yes	9.88
E-CURD-112	no	3.21
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DMBX1, FOXO1, NFKB1, NFKB, NFKBIA, RELA, SSRP1

miRNA regulators (miRDB)

69 targeting TRAF1, 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-4487	99.96	64.58	1252
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-4291	99.20	68.88	2969

Literature-anchored findings (GeneRIF, showing 40)

• Study of regulation of TRAF1, which was overexpressed in B-CLL lymphocytes, shows NF-kappaB/Rel activity in B-CLL nuclear extracts bind to TRAF1 promoter elements and regulation is IKK-independent. (PMID:12411322)
• results suggest that tumor necrosis factor receptor-associated factor 1(TRAF1) exerts regulatory effects on receptor-induced nuclear factor-kappaB activation by targeting inhibitor of kappab kinase complex (PMID:12709429)
• stoichiometry of TRAF1-TRAF2 heteromeric complexes ((TRAF2)2-TRAF1 versus TRAF2-(TRAF1)2) determines their capability to mediate CD40 signaling but has no major effect on TNF signaling (PMID:14557256)
• Actinomycin D blocked PMA-mediated TRAF1 expression in colon cancer cells, suggesting induction at the transcriptional level. (PMID:14981539)
• A constitutive expression of TRAF1, TRAF2, and TANK/I-TRAF in human gliomas was documented (PMID:16304992)
• the t(11, 18)(q21;q21) translocation creating the c-IAP2.MALT1 fusion protein activates NF-kappaB independently of TRAF1 AND TRAF2 and contributes to human malignancy in the absence of signaling adaptors that might otherwise regulate its activity (PMID:16891304)
• The expression of TRAF1 (TNF receptor associated factor 1) in peripheral blood mononuclear cells was significantly decreased in SLE patients. (PMID:17235653)
• Lymphocytes and lymphoma cells from lymphoma-associated NF-kappaB2 mutant transgenic mice express high levels of TRAF1. (PMID:17405906)
• A common genetic variant at the TRAF1-C5 locus on chromosome 9 is associated with an increased risk of anti-CCP-positive rheumatoid arthritis. (PMID:17804836)
• A polymorphism in the TRAF1/C5 region increases the susceptibility to and severity of rheumatoid arthritis. (PMID:17880261)
• Study identifies TRAF1 as a substrate of PKN1 kinase activity in vitro and in vivo, and show that this phosphorylation event is required for attenuating downstream kinase activities. (PMID:18429822)
• STAT4 but not TRAF1/C5 variants influence the risk of developing rheumatoid arthritis and systemic lupus erythematosus in Colombians. (PMID:18432273)
• STAT4 and the TRAF1/C5 loci are associated with rheumatoid arthritis susceptibility. (PMID:18434327)
• TRAF1-C5 locus genetic variant SNP rs3761847 is associated with juvenile idiopathic arthritis (PMID:18576341)
• study concludes that mutant alleles or genotypes of both TRAF1 and STAT4 polymorphisms are associated with the development of Rheumatoid arthritis in our population. (PMID:18625278)
• The risk of death in rheumatoid arthritis is increased in TRAF1/C5 rs3761847 GG homozygotes (PMID:19116907)
• TRAF1 shifts the quality of integrated TNFR1-TNFR2 signaling from apoptosis induction to proinflammatory NFkappaB signaling. (PMID:19287455)
• Association of TRAF1-C5 locus with rheumatoid arthritis susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for systemic lupus erythematosus. (PMID:19336421)
• Genetic markers in the 6q23 region and TRAF1-C5 are associated with rheumatoid arthritis, in particular with positive anti-cyclic citrullinated peptide and rheumatoid factor profile. (PMID:19401279)
• A significant association was found for the TRAF1-C5 locus in systemic lupus erythematosis, implying that this region lies in a pathway relevant to multiple autoimmune diseases. (PMID:19433411)
• Data show that TRAF1 is an important molecule mediating both the CD30 signaling-dependent and independent NF-kappaB activation, which prevents the lymphoma cells from spontaneous and induced apoptosis. (PMID:19540595)
• adiponectin augmented the expression of A20, suppressor of cytokine signaling (SOCS) 3, B-cell CLL/lymphoma (BCL) 3, TNF receptor-associated factor (TRAF) 1, and TNFAIP3-interacting protein (TNIP) 3. (PMID:19617629)
• a role for TRAF1 as a positive regulator of the NF-kappaB alternative pathway. (PMID:19698991)
• TRAF1 single-nucleotide polymorphisms are associated with rheumatoid arthritis in both Asians and Caucasians and are possibly correlated with causative variations. (PMID:19714643)
• Results showed no influence of rs10818488 and rs2900180 TRAF1/C5 gene polymorphisms in susceptibility to and clinical expression of giant cell arteritis. (PMID:19918040)
• results point to the involvement of the TRAF1/C5 locus in the aetiology of familial and severe alopecia areata (AA), and provide further support for a shared aetiology between AA and other autoimmune disorders. (PMID:20030635)
• crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes; biochemical, structural, and cell biological studies on the interaction between TRAF2 and cIAP2 and on the ability of TRAF1 to modulate this interaction (PMID:20385093)
• the human TRAF1 mRNA has an unusually long 5’-UTR that contains internal ribosome entry segment regulating its translation. (PMID:20413583)
• Our results do not show that the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms may confer a direct risk of cardiovascular disease disease in patients with rheumatoid arthritis. (PMID:20822712)
• Interaction of TRAF1 with I-kappa B kinase-2 and TRAF2 is important for regulation of NF-kappa B activity. (PMID:20856938)
• 4-1BBL and TRAF1 in the CD8 T cell response to influenza virus and HIV (PMID:21153322)
• Significant differences in SNPs rs3761847 and rs7021206 at TRAF1/C5 were observed between the case and control groups, the allelic p-value was 0.0018 with an odds ratio of 1.28 for rs3761847 and 0.005 with an odds ratio of 1.27 for rs7021206. (PMID:21492465)
• Death domain SXXE/D motifs of TNFR1-death domain are phosphorylated, as is required for stable TNFR1-TRADD complex formation and subsequent activation of NF-kappaB in inflamed mucosa. (PMID:21724995)
• A genetic association of the TRAF1/C5, C1q, and eNOS gene polymorphism, but not of STAT4 and PTPN22, was found to confer a degree of risk for systemic lupus erythematosus in the Turkish population. (PMID:21968398)
• These findings identify TRAF1 as a potential biomarker of HIV-specific CD8 T cell fitness during the chronic phase of disease and a target for therapy. (PMID:22184633)
• TRAF1 polymorphisms contribute to rheumatoid arthritis susceptibility, activity, and severity in an Egyption population. (PMID:22196377)
• We confirmed the positive association of rs10818488 A allele with rheimatoid arthritis in Tunisia. (PMID:22284611)
• the present data do not support the initial findings that single-nucleotide polymorphisms of TRAF1-C5 and TNFAIP3-OLIG3 rare associated with the severity of joint destruction in RA. (PMID:22586175)
• An association was found between the rs10818488 polymorphism of TRAF1-C5 and susceptibility to systemic lupus erythemaosis in Europeans [Meta-analysis] (PMID:22820624)
• The frequency of TRAF1 rs3761847 and rs2900180 polymorphisms did not differ between patients and controls. (PMID:23125866)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	traf1	ENSDARG00000069482
mus_musculus	Traf1	ENSMUSG00000026875
rattus_norvegicus	Traf1	ENSRNOG00000048914
caenorhabditis_elegans		WBGENE00006612
caenorhabditis_elegans	trf-2	WBGENE00022454

Paralogs (5): TRAF4 (ENSG00000076604), TRAF5 (ENSG00000082512), TRAF2 (ENSG00000127191), TRAF3 (ENSG00000131323), TRAF6 (ENSG00000175104)

Protein

Protein identifiers

TNF receptor-associated factor 1 — Q13077 (reviewed: Q13077)

Alternative names: Epstein-Barr virus-induced protein 6

All UniProt accessions (1): Q13077

UniProt curated annotations — full annotation on UniProt →

Function. Adapter molecule that regulates the activation of NF-kappa-B and JNK. Plays a role in the regulation of cell survival and apoptosis. The heterotrimer formed by TRAF1 and TRAF2 is part of a E3 ubiquitin-protein ligase complex that promotes ubiquitination of target proteins, such as MAP3K14. The TRAF1/TRAF2 complex recruits the antiapoptotic E3 protein-ubiquitin ligases BIRC2 and BIRC3 to TNFRSF1B/TNFR2.

Subunit / interactions. Homotrimer. Heterotrimer with TRAF2. Interacts with TNFRSF1A/TNFR1, TNFRSF1B/TNFR2, TNFRSF4, TNFRSF5/CD40, TNFRSF8/CD30, TNFRSF9/CD137, TNFRSF11A/RANK, TNFRSF13C, TNFRSF18/AITR, TNFRSF17/BCMA, TNFRSF19/TROY, TNFRSF19L/RELT, XEDAR, EDAR, Epstein-Barr virus BNFL1/LMP-1, TANK/ITRAF, TRAIP and RIPK2. Interacts with BIRC2 and BIRC3 N-terminus; a single BIRC2 or BIRC3 molecule interacts with a heterotrimer formed by TRAF1 and TRAF2. Interacts with NFATC2IP, TRAFD1 and with HIVEP3. Interacts with MAP3K14. Interacts with GPS2.

Post-translational modifications. Polyubiquitinated by BIRC2 and/or BIRC3, leading to its subsequent proteasomal degradation. Ubiquitinated by the SCF(FBXL2) complex, leading to its degradation by the proteasome.

Domain organisation. The coiled coil domain mediates homo- and hetero-oligomerization. The MATH/TRAF domain binds to receptor cytoplasmic domains. Cleavage by CASP8 liberates a C-terminal fragment that promotes apoptosis and inhibits the activation of NF-kappa-B in response to TNF signaling.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13077-1	1	yes
Q13077-2	2

RefSeq proteins (3): NP_001177874, NP_001177876, NP_005649* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002083	MATH/TRAF_dom	Domain
IPR008974	TRAF-like	Homologous_superfamily
IPR012227	TNF_rcpt-assoc_TRAF_met	Family
IPR032070	TRAF_BIRC3-bd	Domain
IPR037306	TRAF1_MATH	Domain
IPR049342	TRAF1-6_MATH_dom	Domain

Pfam: PF16673, PF21355

UniProt features (34 total): strand 13, helix 6, mutagenesis site 3, turn 2, cross-link 2, chain 1, domain 1, region of interest 1, coiled-coil region 1, site 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3M0D	X-RAY DIFFRACTION	2.8
5E1T	X-RAY DIFFRACTION	2.8
5H10	X-RAY DIFFRACTION	3.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13077-F1	80.09	0.57

Functional residue map

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

Catalytic / active sites (1): 163–164 (cleavage; by casp8)

Post-translational modifications (3): 146, 185, 193

Mutagenesis-validated functional residues (3):

Position	Phenotype
163	abolishes casp8-mediated cleavage.
185	nearly abolished ubiquitination; when associated with r-193.
193	nearly abolished ubiquitination; when associated with r-185.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway

MSigDB gene sets: 404 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, BIOCARTA_TNFR2_PATHWAY, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_RESPONSE_TO_PEPTIDE, GOLDRATH_IMMUNE_MEMORY, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, HINATA_NFKB_TARGETS_KERATINOCYTE_UP, LINDSTEDT_DENDRITIC_CELL_MATURATION_B, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_APOPTOTIC_SIGNALING_PATHWAY, FOSTER_TOLERANT_MACROPHAGE_UP, PID_TNF_PATHWAY, KEGG_PATHWAYS_IN_CANCER

GO Biological Process (8): apoptotic process (GO:0006915), tumor necrosis factor-mediated signaling pathway (GO:0033209), regulation of canonical NF-kappaB signal transduction (GO:0043122), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), protein-containing complex assembly (GO:0065003), regulation of extrinsic apoptotic signaling pathway (GO:2001236), signal transduction (GO:0007165), regulation of apoptotic process (GO:0042981)

GO Molecular Function (7): tumor necrosis factor receptor binding (GO:0005164), zinc ion binding (GO:0008270), ubiquitin protein ligase binding (GO:0031625), thioesterase binding (GO:0031996), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TNF signaling	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
canonical NF-kappaB signal transduction	1
regulation of intracellular signal transduction	1
cellular component assembly	1
protein-containing complex organization	1
extrinsic apoptotic signaling pathway	1
regulation of apoptotic signaling pathway	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
apoptotic process	1
regulation of programmed cell death	1
tumor necrosis factor receptor superfamily binding	1
transition metal ion binding	1
ubiquitin-like protein ligase binding	1
enzyme binding	1
protein-macromolecule adaptor activity	1
protein binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAF1	BIRC3	Q13489	997
TRAF1	BIRC2	Q13490	997
TRAF1	TRADD	Q15628	994
TRAF1	TNFRSF1B	P20333	989
TRAF1	TNFRSF1A	P19438	978
TRAF1	TNFRSF9	Q07011	950
TRAF1	CD40	P25942	922
TRAF1	XIAP	P98170	914
TRAF1	CFLAR	O15519	902
TRAF1	TNFAIP3	P21580	895
TRAF1	FADD	Q13158	880
TRAF1	TANK	Q92844	875
TRAF1	TNF	P01375	866
TRAF1	RIPK1	Q13546	856
TRAF1	TNFRSF8	P28908	795

IntAct

898 interactions, top by confidence:

A	B	Type	Score
TRAF1	TRAF6	psi-mi:“MI:0915”(physical association)	0.940
MAPRE2	TRAF1	psi-mi:“MI:0915”(physical association)	0.840
TRAF1	NUP58	psi-mi:“MI:0915”(physical association)	0.840
TRAF1	MAPRE2	psi-mi:“MI:0915”(physical association)	0.840
RIPK1	TRAF1	psi-mi:“MI:0915”(physical association)	0.800
TRAF1	RIPK1	psi-mi:“MI:0915”(physical association)	0.800
TRAF1	TCL1A	psi-mi:“MI:0915”(physical association)	0.790
TRAF1	MORN3	psi-mi:“MI:0915”(physical association)	0.790
TRAF1	SCNM1	psi-mi:“MI:0915”(physical association)	0.790
TCL1A	TRAF1	psi-mi:“MI:0915”(physical association)	0.790
TRAF1	PSMB1	psi-mi:“MI:0915”(physical association)	0.780
ZNF440	TRAF1	psi-mi:“MI:0915”(physical association)	0.780
ZNF502	TRAF1	psi-mi:“MI:0915”(physical association)	0.780
ZNF512B	TRAF1	psi-mi:“MI:0915”(physical association)	0.780
METTL17	TRAF1	psi-mi:“MI:0915”(physical association)	0.780
GORASP2	TRAF1	psi-mi:“MI:0915”(physical association)	0.780
PSMB1	TRAF1	psi-mi:“MI:0915”(physical association)	0.780
TRAF1	ZNF440	psi-mi:“MI:0915”(physical association)	0.780
TRAF1	ZNF502	psi-mi:“MI:0915”(physical association)	0.780
CDKN2B	TRAF1	psi-mi:“MI:0915”(physical association)	0.740
CFLAR	TRAF1	psi-mi:“MI:0915”(physical association)	0.720
MOS	TRAF1	psi-mi:“MI:0915”(physical association)	0.720
ZNF20	TRAF1	psi-mi:“MI:0915”(physical association)	0.720
TRAF1	GEM	psi-mi:“MI:0915”(physical association)	0.720
TRAF1	TFAP4	psi-mi:“MI:0915”(physical association)	0.720
TRAF1	STK3	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (541): TRAF1 (Affinity Capture-Western), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF1 (Two-hybrid)

ESM2 similar proteins: A1E2V0, A2AWP0, A6QPT6, A9JTP3, A9ULZ2, B1WBS3, O08863, O14771, O15037, O43918, O94966, P05433, P48778, P51617, Q08DD7, Q0P5G1, Q13077, Q15477, Q2LGB3, Q3TD16, Q3UJD6, Q499Z3, Q4R3B7, Q4R6Y5, Q5RA67, Q5XIS1, Q62210, Q62406, Q6AXX1, Q6J1Y9, Q75NR7, Q80U38, Q80VL3, Q811H0, Q8BHW9, Q8CFK6, Q8JHV9, Q8K330, Q8R2S1, Q8TE77

Diamond homologs: A7XUJ6, B5DF45, B6CJY4, B6CJY5, D3YY23, O13033, O70263, P15919, P39428, P43254, P68907, P70196, P93471, Q02084, Q13077, Q17RB8, Q1L5Z9, Q28DL4, Q3MV19, Q3UWA4, Q3ZCC3, Q6CTZ8, Q6DJN2, Q6IWL4, Q6J2U6, Q6MFY8, Q6Q0C0, Q6ZMN7, Q865W2, Q8TBB1, Q91187, Q922B6, Q9D4H7, Q9D9R0, Q9ET26, Q9FNI6, Q9Y4K3, P15918, P39429, Q1XHT8

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
LUBAC	“up-regulates activity”	TRAF1	polyubiquitination
TNFRSF1B	up-regulates	TRAF1	binding
TNFRSF1B	up-regulates	TRAF1
TRAF1	up-regulates	TRAF2	binding
TRAF2	up-regulates	TRAF1	binding
NFKB1	“up-regulates quantity by expression”	TRAF1	“transcriptional regulation”
RELA	“up-regulates quantity by expression”	TRAF1	“transcriptional regulation”
TRADD	up-regulates	TRAF1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1712 predictions. Top by Δscore:

Variant	Effect	Δscore
9:120905235:TGACC:T	acceptor_loss	1.0000
9:120905236:GACC:G	acceptor_loss	1.0000
9:120905237:ACCT:A	acceptor_loss	1.0000
9:120905238:CCTG:C	acceptor_loss	1.0000
9:120905239:C:CG	acceptor_loss	1.0000
9:120905240:T:A	acceptor_loss	1.0000
9:120909225:CATA:C	donor_loss	1.0000
9:120909228:A:T	donor_loss	1.0000
9:120909229:C:CA	donor_loss	1.0000
9:120909268:C:CA	donor_gain	1.0000
9:120909269:C:A	donor_gain	1.0000
9:120911330:TGTTA:T	donor_loss	1.0000
9:120911331:GTTAC:G	donor_loss	1.0000
9:120911332:TTACC:T	donor_loss	1.0000
9:120911333:TA:T	donor_loss	1.0000
9:120911334:A:C	donor_loss	1.0000
9:120911335:C:CA	donor_loss	1.0000
9:120913326:AC:A	donor_gain	1.0000
9:120913327:CC:C	donor_gain	1.0000
9:120913327:CCCT:C	donor_gain	1.0000
9:120925031:T:TA	donor_gain	1.0000
9:120928485:T:TA	donor_gain	1.0000
9:120928547:AT:A	donor_gain	1.0000
9:120905239:C:CC	acceptor_gain	0.9900
9:120909374:GAAGG:G	acceptor_gain	0.9900
9:120909376:AGG:A	acceptor_gain	0.9900
9:120909377:GG:G	acceptor_gain	0.9900
9:120909379:C:CC	acceptor_gain	0.9900
9:120909379:C:CG	acceptor_loss	0.9900
9:120911510:CCAC:C	acceptor_gain	0.9900

AlphaMissense

2722 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:120905123:C:T	G383E	1.000
9:120905158:G:C	F371L	1.000
9:120905158:G:T	F371L	1.000
9:120905160:A:G	F371L	1.000
9:120909245:C:A	W339C	1.000
9:120909245:C:G	W339C	1.000
9:120909247:A:G	W339R	1.000
9:120909247:A:T	W339R	1.000
9:120909287:G:C	F325L	1.000
9:120909287:G:T	F325L	1.000
9:120909289:A:G	F325L	1.000
9:120909324:C:T	G313E	1.000
9:120905041:G:C	C410W	0.999
9:120905150:G:T	P374H	0.999
9:120905151:G:A	P374S	0.999
9:120905185:G:C	F362L	0.999
9:120905185:G:T	F362L	0.999
9:120905186:A:G	F362S	0.999
9:120905187:A:G	F362L	0.999
9:120905225:A:G	L349P	0.999
9:120909289:A:C	F325V	0.999
9:120909289:A:T	F325I	0.999
9:120909324:C:A	G313V	0.999
9:120909357:C:A	G302V	0.999
9:120909357:C:T	G302D	0.999
9:120911408:A:G	W271R	0.999
9:120911408:A:T	W271R	0.999
9:120905043:A:G	C410R	0.998
9:120905050:G:C	F407L	0.998
9:120905050:G:T	F407L	0.998

dbSNP variants (sampled 300 via entrez): RS1000014800 (9:120917455 G>A), RS1000080761 (9:120911232 A>G), RS1000081746 (9:120917779 T>C), RS1000157228 (9:120923082 G>A), RS1000267854 (9:120911507 C>A,T), RS1000269439 (9:120917443 C>A,G), RS1000355852 (9:120929186 C>A), RS1000623540 (9:120922281 G>T), RS1000659592 (9:120918511 A>G), RS1000677818 (9:120928483 C>T), RS1000725667 (9:120917105 C>T), RS1000789073 (9:120929040 C>T), RS1000870209 (9:120909892 G>A,T), RS1000899712 (9:120905859 G>A), RS1001010177 (9:120918876 C>T)

Disease associations

OMIM: gene MIM:601711 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000420_1	Rheumatoid arthritis	4.000000e-08
GCST000987_6	Celiac disease or Rheumatoid arthritis	4.000000e-11
GCST002318_159	Rheumatoid arthritis	5.000000e-11
GCST002318_160	Rheumatoid arthritis	4.000000e-09
GCST002434_4	Rheumatoid arthritis	3.000000e-09
GCST004627_3	Lymphocyte count	9.000000e-11
GCST005038_131	Allergic disease (asthma, hay fever or eczema)	5.000000e-09
GCST005568_39	Rheumatoid arthritis (ACPA-positive)	2.000000e-08
GCST005568_7	Rheumatoid arthritis (ACPA-positive)	2.000000e-06
GCST005569_13	Rheumatoid arthritis	4.000000e-07
GCST006048_8	Rheumatoid arthritis (ACPA-positive)	4.000000e-12
GCST007269_179	Pulse pressure	4.000000e-10
GCST007843_17	Rheumatoid arthritis	6.000000e-09
GCST010002_279	Refractive error	2.000000e-11
GCST010042_44	Asthma	5.000000e-09
GCST010043_166	Asthma	1.000000e-12
GCST90002382_274	Eosinophil percentage of white cells	4.000000e-09
GCST90002388_226	Lymphocyte count	1.000000e-21
GCST90002389_353	Lymphocyte percentage of white cells	3.000000e-09
GCST90002407_123	White blood cell count	3.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0005763	pulse pressure measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3761847	Efficacy	3	adalimumab;etanercept;infliximab;Tumor necrosis factor alpha (TNF-alpha) inhibitors	Rheumatoid arthritis

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1081848	TRAF1		0.00	0
rs3761847	TRAF1	3	2.25	1	adalimumab;etanercept;infliximab;Tumor necrosis factor alpha (TNF-alpha) inhibitors

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	increases expression	4
Air Pollutants	increases abundance, increases expression, affects expression	3
Curcumin	decreases reaction, increases expression, decreases expression	3
Folic Acid	affects expression, affects response to substance, affects cotreatment, increases expression	3
sodium arsenite	decreases expression	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	2
polyhexamethyleneguanidine	affects expression, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Lipopolysaccharides	increases expression, affects expression, affects response to substance, affects cotreatment	2
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases expression, affects binding, increases reaction	2
Asbestos, Crocidolite	affects expression, increases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
parthenolide	increases expression, decreases expression, decreases reaction	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
indole-3-carbinol	decreases reaction, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
dioscin	increases expression	1
rhein	increases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases reaction, increases expression	1
pregna-4,17-diene-3,16-dione	increases expression, decreases reaction	1
bathocuproine sulfonate	affects cotreatment, decreases reaction, increases expression	1
nickel sulfate	increases expression	1
1’-acetoxychavicol acetate	decreases reaction, increases expression	1
CGP 52608	increases reaction, affects binding	1
lonafarnib	decreases reaction, increases expression	1

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8RB	Abcam HCT 116 TRAF1 KO	Cancer cell line	Male
CVCL_B9TQ	Abcam A-549 TRAF1 KO	Cancer cell line	Male
CVCL_D2HK	Abcam MCF-7 TRAF1 KO	Cancer cell line	Female
CVCL_D8CX	Ubigene A-549 TRAF1 KO	Cancer cell line	Male
CVCL_E0RZ	Ubigene HeLa TRAF1 KO	Cancer cell line	Female
CVCL_TT53	HAP1 TRAF1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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