TRAF3

Summary

TRAF3 (TNF receptor associated factor 3, HGNC:12033) is a protein-coding gene on chromosome 14q32.32, encoding TNF receptor-associated factor 3 (Q13114). Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types.

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from, members of the TNF receptor (TNFR) superfamily. This protein participates in the signal transduction of CD40, a TNFR family member important for the activation of the immune response. This protein is found to be a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex, which induces NF-kappaB activation and cell death initiated by LTbeta ligation. Epstein-Barr virus encoded latent infection membrane protein-1 (LMP1) can interact with this and several other members of the TRAF family, which may be essential for the oncogenic effects of LMP1. The protein also plays a role in the regulation of antiviral response. Mutations in this are associated with Encephalopathy, acute, infection-induced, herpes-specific 5.

Source: NCBI Gene 7187 — RefSeq curated summary.

At a glance

• Gene–disease (curated): herpes simplex encephalitis, susceptibility to, 3 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 38
• Clinical variants (ClinVar): 420 total — 7 pathogenic
• Phenotypes (HPO): 85
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_145725

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12033
Approved symbol	TRAF3
Name	TNF receptor associated factor 3
Location	14q32.32
Locus type	gene with protein product
Status	Approved
Aliases	CAP-1, CD40bp, CRAF1, LAP1, RNF118
Ensembl gene	ENSG00000131323
Ensembl biotype	protein_coding
OMIM	601896
Entrez	7187

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 21 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000351691, ENST00000392745, ENST00000539721, ENST00000558700, ENST00000558880, ENST00000559734, ENST00000560371, ENST00000560463, ENST00000699893, ENST00000699894, ENST00000699895, ENST00000699896, ENST00000699897, ENST00000860914, ENST00000860915, ENST00000860916, ENST00000860917, ENST00000860918, ENST00000860919, ENST00000860920, ENST00000939074, ENST00000939075, ENST00000952335, ENST00000952336, ENST00000952337, ENST00000952338

RefSeq mRNA: 6 — MANE Select: NM_145725 NM_001199427, NM_001385142, NM_001385143, NM_003300, NM_145725, NM_145726

CCDS: CCDS55946, CCDS9975, CCDS9976

Canonical transcript exons

ENST00000392745 — 12 exons

Exon	Start	End
ENSE00000660513	102871917	102871968
ENSE00000660514	102875624	102875728
ENSE00000660515	102876358	102876525
ENSE00000660516	102886189	102886269
ENSE00000660517	102889560	102889634
ENSE00000660518	102891325	102891417
ENSE00000660519	102897261	102897401
ENSE00000660520	102903255	102903429
ENSE00001026101	102870185	102870446
ENSE00001512975	102830334	102830472
ENSE00002542734	102777449	102777675
ENSE00003902922	102905213	102911500

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 90.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2538 / max 282.6214, expressed in 1774 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141676	9.9346	1739
141675	1.3192	862

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	90.51	gold quality
monocyte	CL:0000576	88.35	gold quality
mononuclear cell	CL:0000842	87.98	gold quality
leukocyte	CL:0000738	87.76	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.69	gold quality
vermiform appendix	UBERON:0001154	87.68	gold quality
middle temporal gyrus	UBERON:0002771	87.53	gold quality
granulocyte	CL:0000094	87.17	gold quality
postcentral gyrus	UBERON:0002581	86.70	gold quality
lymph node	UBERON:0000029	86.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.03	gold quality
tibia	UBERON:0000979	85.85	gold quality
epithelium of nasopharynx	UBERON:0001951	85.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.53	gold quality
bronchial epithelial cell	CL:0002328	85.44	gold quality
secondary oocyte	CL:0000655	85.27	gold quality
parietal lobe	UBERON:0001872	85.16	gold quality
endothelial cell	CL:0000115	85.00	silver quality
bone marrow cell	CL:0002092	84.98	gold quality
superior frontal gyrus	UBERON:0002661	84.87	gold quality
parietal pleura	UBERON:0002400	84.73	gold quality
stromal cell of endometrium	CL:0002255	84.61	gold quality
caecum	UBERON:0001153	84.60	gold quality
pleura	UBERON:0000977	83.92	gold quality
tonsil	UBERON:0002372	83.39	gold quality
blood	UBERON:0000178	83.35	gold quality
calcaneal tendon	UBERON:0003701	83.17	gold quality
epithelium of bronchus	UBERON:0002031	83.02	gold quality
visceral pleura	UBERON:0002401	83.02	gold quality
islet of Langerhans	UBERON:0000006	82.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.06
E-GEOD-75367	no	61.65

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
IL10	Activation

Upstream regulators (CollecTRI, top): RELB, TAL1

miRNA regulators (miRDB)

269 targeting TRAF3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-9-5P	100.00	72.28	2361
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-4283	100.00	66.42	2097
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6759-5P	99.99	66.54	785

Literature-anchored findings (GeneRIF, showing 40)

• The TRAF domain from TRAF3 has been crystallized. (PMID:12136149)
• results suggest that in DG75 cells, TRAF3-induced MEK1 activation may be involved in CD40-mediated upregulation of IL-4-driven germline C epsilon transcription (PMID:12220533)
• Results establish a major role of TRAF3 and -6 in X-linked ectodermal dysplasia receptor (XEDAR) signaling and in the process of ectodermal differentiation. (PMID:12270937)
• TRAF3 interacts with BAFFR in yeast two-hybrid assays and in TALL-1-treated B lymphoma cells and is a negative regulator of BAFFR-mediated NF-kappa B activation and IL-10 production. (PMID:12471121)
• TRAF2, TRAF3, cIAP1, Smac, and lymphotoxin beta receptor associate and are involved in apoptosis (PMID:12571250)
• EBV LMP1 blocks p16INK4 pathway by promoting nuclear export of E2F-4 and E2F-5. (PMID:12860972)
• the TRAF3-binding crevice has hot spots that promote molecular interactions driving specific signaling after contact with LTbetaR, CD40, or the downstream regulator TANK (PMID:14517219)
• LMP1 associated protein induces micronucleus formation, represses DNA repair and enhances sensitivity to DNA-damaging agents in human epithelial cells. (PMID:14716302)
• induction of noncanonical NF-kappaB signaling may involve the rescue of NIK from TRAF3-mediated negative regulation (PMID:15084608)
• there is a novel association between TRAF2 and TRAF3 that is mediated by unique portions of each protein and that specifically regulates activation of NF-kappaB, but not AP-1 (PMID:15383523)
• LMP-1 proteins are required for in vitro growth of non-Hodgkin lymphoma cells. (PMID:15514968)
• This study of the crystal structure of TRAF3 bound in complex with BAFF-R reveals the dynamic conformational adjustment of Tyr377 in TRAF3 that occurs forming a new intermolecular contact with BAFF-R that stabilizes the complex. (PMID:15585864)
• TRAF3 specifically blocked the NF-kappaB activation via TRAF2/5. (PMID:15708970)
• LMP1 from the Epstein-Barr virus is a structural CD40 decoy in B lymphocytes for binding to TRAF3. (PMID:16009714)
• LMP1 utilizes two distinct pathways to activate NF-kappaB: a major one through CTAR2/TRAF6/TAK1/IKKbeta (canonical pathway) and a minor one through CTAR1/TRAF3/NIK/IKKalpha (noncanonical pathway) (PMID:16280329)
• These data indicate that vFLIP uses TRAF2 and TRAF3 for signalling to NF-kappaB, which is crucial for KSHV-associated lymphomagenesis (PMID:16311516)
• TRAF3 stabilization, JNK activation and caspase-9 induction define a novel pathway of CD40-mediated apoptosis in carcinoma cells. (PMID:16429118)
• TRAF3 has a role in innate antiviral immunity [review] (PMID:16582590)
• TRAF3, like Cardif, is required for type I interferon production in response to intracellular double-stranded RNA. (PMID:16858409)
• The current data support the notion that LMP1 modifies stress-induced apoptosis in epithelial cells through molecular interactions downstream of its C-terminal signaling domain. (PMID:17586463)
• Results show that decrease in the ubiquitination of TRAF3 is YopJ-dependent and to prevent or is to remove the K63-polymerized ubiquitin conjugates required for signal transduction. (PMID:17608743)
• Dominant-negative forms of TRAF2 and TRAF3 inhibited but did not fully block LMP1-mediated transformation. (PMID:17626074)
• Inactivation of TRAF3 is associated with multiple myeloma (PMID:17692805)
• LMP1’s activation of the unfolded protein response is a normal event in a continuum of LMP1’s expression that leads both to stimulatory and inhibitory functions and regulates the physiology of epstein barr virus-infected B cells. (PMID:18042799)
• The researchers found an association between LMP1 30-bp deletion or XhoI-loss with Chinese race and type III nasopharyngeal carcinoma. (PMID:18275617)
• Somatic mutation of TRAF3 gene is rare in common human cancers and acute leukemias. (PMID:18607851)
• These findings indicate that the NY-1V Hantavirus Gn cytoplasmic tail forms a complex with TRAF3 which disrupts the formation of TBK1-TRAF3 complexes and downstream signaling responses required for IFN-beta transcription. (PMID:18614628)
• c-Src enhances RIG-I-mediated signaling, acting at the level of TRAF3 (PMID:19419966)
• TRAF2/3 binding affinity and TRAF2/3 binding site sequence dictate a distinct subset of CD40 antigen versus latent membrane protein 1 (LMP1) signaling properties. (PMID:19667091)
• biallelic inactivation of TRAF3 and lower expression of its mRNA occures with del(14) due to breaks in IGH and ZEP36L1 regions (PMID:19693093)
• Triad3A represents a versatile E3 ubiquitin ligase that negatively regulates RIG-like receptor signaling by targeting TRAF3 for degradation following RNA virus infection. (PMID:19893624)
• Lack of TRAF3 expression might be one of the reasons for the aberrant expression of the unclassical NF-kappaB activity in Hodgkin’s lymphoma cells. (PMID:19954665)
• Findings suggest that OTUB1 and OTUB2 negatively regulate virus-triggered type I IFN induction and cellular antiviral response by deubiquitinating TRAF3 and -6. (PMID:19996094)
• CD40L induces apoptosis by influencing the balance between apoptotic and survival signals, by stabilizing TRAF3 to induce apoptosis and by suppressing TRAF6 survival signals (PMID:20008286)
• virus-triggered ubiquitination of TRAF3 and TRAF6 by cIAP1 and cIAP2 is essential for type I IFN induction and cellular antiviral response (PMID:20097753)
• Data found that BS69 directly interacted with TRAF3, a negative regulator of NF-kappaB activation. Results revealed that TRAF3 was involved in the BS69-mediated suppression of LMP1/CTAR1-induced NF-kappaB activation. (PMID:20138174)
• Modulation of cellular TRAF3 levels may thus contribute to regulation of NFkappaB-dependent gene expression by LTBR by affecting the balance of LTBR-dependent activation of canonical and non-canonical NFkappaB pathways. (PMID:20185819)
• the LTbetaR modifies the ubiquitin:NIK E3 ligase, and also acts as an allosteric regulator of the ubiquitin:TRAF E3 ligase (PMID:20348096)
• An association was found between MGP -7A>G and CD40 -1C>T polymorphisms, and reocclusion risk. (PMID:20504251)
• Taken together, LMP1 activates alternative NF-kappaB pathway through functional NIK and IKKalpha that is regulated by TRAF2 or TRAF3. (PMID:20585848)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Traf3	ENSMUSG00000021277
rattus_norvegicus	Traf3	ENSRNOG00000008145
caenorhabditis_elegans		WBGENE00006612
caenorhabditis_elegans	trf-2	WBGENE00022454

Paralogs (5): TRAF1 (ENSG00000056558), TRAF4 (ENSG00000076604), TRAF5 (ENSG00000082512), TRAF2 (ENSG00000127191), TRAF6 (ENSG00000175104)

Protein

Protein identifiers

TNF receptor-associated factor 3 — Q13114 (reviewed: Q13114)

Alternative names: CD40 receptor-associated factor 1, CD40-binding protein, LMP1-associated protein 1, RING-type E3 ubiquitin transferase TRAF3

All UniProt accessions (5): A6NHG8, Q13114, H0YL25, H0YL26, H0YMI8

UniProt curated annotations — full annotation on UniProt →

Function. Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types. In TLR and RLR signaling pathways, acts as an E3 ubiquitin ligase promoting the synthesis of ‘Lys-63’-linked polyubiquitin chains on several substrates such as ASC that lead to the activation of the type I interferon response or the inflammasome. Following the activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B regulator, possibly to avoid unregulated inflammatory response, and its degradation via ‘Lys-48’-linked polyubiquitination is required for MAPK activation and production of inflammatory cytokines. Alternatively, when TLR4 orchestrates bacterial expulsion, TRAF3 undergoes ‘Lys-33’-linked polyubiquitination and subsequently binds to RALGDS, mobilizing the exocyst complex to rapidly expel intracellular bacteria back for clearance. Also acts as a constitutive negative regulator of the alternative NF-kappa-B pathway, which controls B-cell survival and lymphoid organ development. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14.

Subunit / interactions. Homotrimer. Heterotrimer with TRAF2 and TRAF5. Interacts with LTBR/TNFRSF3, TNFRSF4, TNFRSF5/CD40, TNFRSF8/CD30, TNFRSF13C TNFRSF17/BCMA, TLR4 and EDAR. Interacts with MAP3K5, MAP3K14, TRAIP/TRIP, TDP2/TTRAP, TANK/ITRAF and TRAF3IP1. Interaction with TNFRSF5/CD40 is modulated by TANK/ITRAF, which competes for the same binding site. Interacts with TICAM1. Interacts with TRAFD1. Interacts with OTUB1, OTUB2 and OTUD5. Interacts with RNF216, OPTN and TBK1. Identified in a complex with TRAF2, MAP3K14 and BIRC3. Interacts with BIRC2 and BIRC3. Upon exposure to bacterial lipopolysaccharide (LPS), recruited to a transient complex containing TLR4, TRAF3, TRAF6, IKBKG, MAP3K7, MYD88, TICAM1, BIRC2, BIRC3 and UBE2N. Interacts (via RING-type zinc finger domain) with SRC. Interacts with CARD14. Interacts (via MATH domain) with PTPN22; the interaction promotes TRAF3 polyubiquitination. Interacts with MAVS. Directly interacts with DDX3X; this interaction stimulates TRAF3 ‘Lys-63’ ubiquitination. Interacts with IRF3. Interacts with IKBKE in the course of Sendai virus infection. Interacts with TRIM35. Interacts with GAPDH; promoting TRAF3 ubiquitination. Interacts with PPP3CA and PPP3CB. Interacts with ATP1B1; promoting TRAF3 ubiquitination. Interacts with RALGDS. Interacts with FBXO11. (Microbial infection) Interacts (via N-terminus) with New York hantavirus glycoprotein N (via C-terminus); this interaction inhibits the formation of TRAF3-TBK1 complexes. (Microbial infection) Interacts with Andes hantavirus glycoprotein N (via C-terminus); this interaction inhibits the formation of TRAF3-TBK1 complexes. (Microbial infection) Interacts with Tula hantavirus glycoprotein N (via C-terminus); this interaction inhibits the formation of TRAF3-TBK1 complexes. (Microbial infection) Interacts with Epstein-Barr virus protein LMP1.

Subcellular location. Cytoplasm. Endosome. Mitochondrion.

Post-translational modifications. Undergoes ‘Lys-48’-linked polyubiquitination, leading to its proteasomal degradation in response to signaling by TNFSF13B, TLR4 or through CD40. ‘Lys-48’-linked polyubiquitinated form is deubiquitinated by OTUD7B, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B. Undergoes ‘Lys-63’-linked ubiquitination during early stages of virus infection, and ‘Lys-48’-linked ubiquitination during later stages. Undergoes both ‘Lys-48’-linked and ‘Lys-63’-linked ubiquitination in response to TLR3 and TLR4 signaling. ‘Lys-63’-linked ubiquitination can be mediated by TRIM35. Deubiquitinated by OTUB1, OTUB2 and OTUD5. Undergoes ‘Lys-63’-linked deubiquitination by MYSM1 to terminate the pattern-recognition receptors/PRRs pathways. Also undergoes ‘Lys-29’-linked ubiquitination on Cys-56 and Cys-124 by NEDD4L; leading to increased ‘Lys-48’- and ‘Lys-63’-linked ubiquitination as well as increased binding to TBK1. TLR4 signals emanating from bacteria containing vesicles trigger ‘Lys-33’-linked polyubiquitination that promotes the assembly of the exocyst complex thereby connecting innate immune signaling to the cellular trafficking apparatus. Deubiquitinated by USP25 during viral infection, leading to TRAF3 stabilization and type I interferon production. Ubiquitinated at Lys-329 by the SCF(FBXL2) complex, leading to its degradation by the proteasome. ‘Lys-63’-linked ubiquitination by FBXO11 in a NEDD8-dependent manner promotes the amplification of IFN-I signaling. (Microbial infection) Cleaved by enterovirus D68 protease 2A; leading to inhibition of NF-kappa-B or IFN-beta triggered by TRAF3.

Disease relevance. Immunodeficiency 132A (IMD132A) [MIM:614849] An autosomal dominant immunologic disorder characterized by increased susceptibility to infection with certain pathogens, including Herpes simplex virus and Mycobacterium abscessus. Immunologic work-up shows impaired production of cytokines, including INFB and IL6. The disease is caused by variants affecting the gene represented in this entry. Immunodeficiency 132B (IMD132B) [MIM:621096] An autosomal dominant immune disorder characterized by childhood onset of recurrent upper and lower respiratory infections, B-cell lymphoid hyperplasia, and dysregulation of T-cell subsets and function. Additional variable features include autoimmunity, autoinflammation, and hyper- or hypogammaglobulinemia. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The MATH/TRAF domain binds to receptor cytoplasmic domains. The Ring-type zinc finger domain is required for its function in down-regulation of NFKB2 proteolytic processing.

Similarity. Belongs to the TNF receptor-associated factor family. A subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13114-1	1	yes
Q13114-2	2

RefSeq proteins (6): NP_001186356, NP_001372071, NP_001372072, NP_003291, NP_663777, NP_663778 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001293	Znf_TRAF	Domain
IPR001841	Znf_RING	Domain
IPR002083	MATH/TRAF_dom	Domain
IPR008974	TRAF-like	Homologous_superfamily
IPR012227	TNF_rcpt-assoc_TRAF_met	Family
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR027128	TRAF3_RING-HC	Domain
IPR037304	TRAF3_MATH	Domain
IPR049342	TRAF1-6_MATH_dom	Domain
IPR049440	TRAF3/5_RING	Domain

Pfam: PF02176, PF21355, PF21363

UniProt features (64 total): strand 14, mutagenesis site 12, helix 7, sequence variant 6, turn 6, sequence conflict 5, cross-link 4, zinc finger region 3, region of interest 2, chain 1, domain 1, splice variant 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
8T5P	X-RAY DIFFRACTION	2.5
2GKW	X-RAY DIFFRACTION	2.7
1FLK	X-RAY DIFFRACTION	2.8
1ZMS	X-RAY DIFFRACTION	2.8
8ZUK	ELECTRON MICROSCOPY	2.83
1L0A	X-RAY DIFFRACTION	2.9
1FLL	X-RAY DIFFRACTION	3.5
1KZZ	X-RAY DIFFRACTION	3.5
1RF3	X-RAY DIFFRACTION	3.5
2ECY	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13114-F1	88.26	0.72

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 (5): 124, 168, 329, 9, 56

Mutagenesis-validated functional residues (12):

Position	Phenotype
56	strong increase in both ’lys-48’ and ’lys-63’-linked ubiquitination.
68–70	loss of ubiquitination activity, impaired interaction with mavs and irf3. no effect on interaction with ikbke, nor with
68	loss of ubiquitination activity on asc; when associated with a-70.
70	loss of ubiquitination activity on asc; when associated with a-68.
124	strong increase in both ’lys-48’ and ’lys-63’-linked ubiquitination.
168	abolishes interaction with ralgds.
441	abolishes interaction with rnf216; when associated with a-443.
443	abolishes interaction with rnf216; when associated with a-441.
459	abolishes interaction with ltbr, cd40 and tank.
462	confers resistance to cleavage by enterovirus d68 protease 2a.
512	abolishes interaction with ltbr, cd40 and tank.
521	abolishes interaction with ltbr, cd40 and tank.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-5602571	TRAF3 deficiency - HSE
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway
R-HSA-5676594	TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
R-HSA-5689896	Ovarian tumor domain proteases
R-HSA-9013973	TICAM1-dependent activation of IRF3/IRF7
R-HSA-918233	TRAF3-dependent IRF activation pathway
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling
R-HSA-936964	Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-9824878	Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7
R-HSA-9828211	Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation

MSigDB gene sets: 605 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, BIOCARTA_TNFR2_PATHWAY, AGGAAGC_MIR5163P, AP1_01, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, MORI_IMMATURE_B_LYMPHOCYTE_UP, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, BROWNE_HCMV_INFECTION_16HR_UP

GO Biological Process (23): regulation of cytokine production (GO:0001817), toll-like receptor signaling pathway (GO:0002224), apoptotic process (GO:0006915), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), Toll signaling pathway (GO:0008063), regulation of proteolysis (GO:0030162), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), positive regulation of type I interferon production (GO:0032481), regulation of interferon-beta production (GO:0032648), tumor necrosis factor-mediated signaling pathway (GO:0033209), toll-like receptor 4 signaling pathway (GO:0034142), TRIF-dependent toll-like receptor signaling pathway (GO:0035666), regulation of apoptotic process (GO:0042981), regulation of canonical NF-kappaB signal transduction (GO:0043122), regulation of defense response to virus (GO:0050688), defense response to virus (GO:0051607), type I interferon-mediated signaling pathway (GO:0060337), immune system process (GO:0002376), mRNA transcription (GO:0009299), regulation of type I interferon production (GO:0032479), innate immune response (GO:0045087), antiviral innate immune response (GO:0140374)

GO Molecular Function (14): ubiquitin-protein transferase activity (GO:0004842), tumor necrosis factor receptor binding (GO:0005164), zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), ubiquitin protein ligase binding (GO:0031625), thioesterase binding (GO:0031996), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), enzyme binding (GO:0019899), metal ion binding (GO:0046872)

GO Cellular Component (10): ubiquitin ligase complex (GO:0000151), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endosome (GO:0005768), cytosol (GO:0005829), cytoplasmic side of plasma membrane (GO:0009898), endosome membrane (GO:0010008), CD40 receptor complex (GO:0035631), serine/threonine protein kinase complex (GO:1902554), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
DDX58/IFIH1-mediated induction of interferon-alpha/beta	2
Diseases associated with the TLR signaling cascade	1
Cytokine Signaling in Immune system	1
TNFR2 non-canonical NF-kB pathway	1
Deubiquitination	1
Toll Like Receptor 3 (TLR3) Cascade	1
TRIF (TICAM1)-mediated TLR4 signaling	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1
TICAM1-dependent activation of IRF3/IRF7	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of type I interferon production	2
protein binding	2
cytoplasm	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
pattern recognition receptor signaling pathway	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
cell surface receptor signaling pathway	1
proteolysis	1
regulation of protein metabolic process	1
positive regulation of cytokine production	1
type I interferon production	1
interferon-beta production	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
cell surface toll-like receptor signaling pathway	1
MyD88-independent toll-like receptor signaling pathway	1
apoptotic process	1
regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of intracellular signal transduction	1
regulation of response to biotic stimulus	1
regulation of defense response	1
regulation of response to external stimulus	1
defense response to virus	1
defense response	1
response to virus	1
cellular response to type I interferon	1
interferon-mediated signaling pathway	1
biological_process	1

Protein interactions and networks

STRING

2708 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAF3	TANK	Q92844	998
TRAF3	TBK1	Q9UHD2	998
TRAF3	BIRC2	Q13490	998
TRAF3	IKBKE	Q14164	998
TRAF3	CHUK	O15111	996
TRAF3	MAVS	Q7Z434	996
TRAF3	BIRC3	Q13489	995
TRAF3	MYD88	P78397	995
TRAF3	TRADD	Q15628	994
TRAF3	IRAK1	P51617	994
TRAF3	IRAK4	Q9NWZ3	994
TRAF3	CD40	P25942	992
TRAF3	TRAF6	Q9Y4K3	990
TRAF3	IRF7	Q92985	987
TRAF3	HRAS	P01112	986

IntAct

227 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
MAVS	RIGI	psi-mi:“MI:0914”(association)	0.920
TRAF3	MAP3K14	psi-mi:“MI:0915”(physical association)	0.920
MAP3K14	IKBKB	psi-mi:“MI:0914”(association)	0.900
TRAF3	TANK	psi-mi:“MI:0407”(direct interaction)	0.870
TRAF3	TANK	psi-mi:“MI:0915”(physical association)	0.870
IL1RAP	IL1B	psi-mi:“MI:0914”(association)	0.760
SNAP29	TRAF3	psi-mi:“MI:0915”(physical association)	0.740
ETV6	LRP6	psi-mi:“MI:0914”(association)	0.730
TRAF3	RIPK1	psi-mi:“MI:0915”(physical association)	0.700
TRAF3	TBK1	psi-mi:“MI:0915”(physical association)	0.690
TBK1	TRAF3	psi-mi:“MI:0914”(association)	0.690
TBK1		psi-mi:“MI:0914”(association)	0.680
LTBR	TRAF3	psi-mi:“MI:0915”(physical association)	0.670
TRAF3	EDA2R	psi-mi:“MI:0915”(physical association)	0.670
TRAF5	TRAF3	psi-mi:“MI:0915”(physical association)	0.660
TRAF3	TRAF3IP1	psi-mi:“MI:0915”(physical association)	0.640
TRAF3IP1	TRAF3	psi-mi:“MI:0915”(physical association)	0.640
TRAF3IP1	TRAF3	psi-mi:“MI:0403”(colocalization)	0.640
ETV6	LRP5	psi-mi:“MI:0914”(association)	0.640
ECH1	ECI2	psi-mi:“MI:0914”(association)	0.620

BioGRID (558): TRAF3 (Affinity Capture-Western), TRAF3 (Two-hybrid), TRAF3 (Affinity Capture-Western), TRAF3 (Two-hybrid), TRAF3 (Reconstituted Complex), TRAF3 (Affinity Capture-Western), TRAF3 (Affinity Capture-Western), TRAF3 (Affinity Capture-MS), TRAF3 (Affinity Capture-MS), TRAF3 (Affinity Capture-MS), TRAF3 (Affinity Capture-MS), TRAF3 (Affinity Capture-MS), TRAF3 (Affinity Capture-MS), IFIT3 (Affinity Capture-Western), TRAF3 (Co-localization)

ESM2 similar proteins: A0A974CYQ5, A5WW08, A7XUJ6, B5DF45, B6CJY4, B6CJY5, O00463, O15344, O70583, P0DW87, P0DW89, P39429, P53351, P70191, P70196, P82457, P82458, Q08CH8, Q12933, Q13114, Q28DL4, Q29RQ5, Q2TAD9, Q3KPU8, Q3MV19, Q3U9F6, Q3ZCC3, Q5FWP4, Q5R4L1, Q60803, Q61382, Q6DJN2, Q6GNX1, Q6IWL4, Q6J1I7, Q6P256, Q80WG7, Q8N2W9, Q91ZY8, Q969K3

Diamond homologs: A7XUJ6, B5DF45, B6CJY4, B6CJY5, D3YY23, O13033, O70263, P15918, P15919, P39428, P43254, P68907, P70196, P93471, Q13077, Q13114, Q17RB8, Q1L5Z9, Q28DL4, Q3MV19, Q3UWA4, Q3ZCC3, Q5D7J2, Q6CTZ8, Q6DJN2, Q6IWL4, Q6J2U6, Q6MFY8, Q6ZMN7, Q867B5, Q8TBB1, Q91187, Q9D4H7, Q9ET26, Q9FNI6, Q9Y4K3, O00463, P39429, P70191, Q12933

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
TNFRSF13C	“down-regulates quantity by destabilization”	TRAF3	binding
CD40	“up-regulates activity”	TRAF3	binding
TRAF3	“up-regulates activity”	TBK1	binding
9b	“down-regulates quantity by destabilization”	TRAF3
“Papain-like proteinase”	“down-regulates activity”	TRAF3	deubiquitination
OTUD5	“down-regulates activity”	TRAF3	deubiquitination
Ub:E2	“up-regulates activity”	TRAF3	ubiquitination
CSNK1E	“up-regulates activity”	TRAF3	phosphorylation
PTPN6	“down-regulates activity”	TRAF3	dephosphorylation
NEDD4L	“up-regulates activity”	TRAF3	ubiquitination
TRAF3	“down-regulates quantity by destabilization”	MAP3K14	ubiquitination
TRAF3	“up-regulates activity”	MAP3K7	ubiquitination
TRAF3	“down-regulates quantity by destabilization”	MAP3K14	binding
TRAF3	“up-regulates quantity by expression”	IL10	“transcriptional regulation”
MYD88	“up-regulates activity”	TRAF3	binding
TNIP1	“down-regulates activity”	TRAF3	binding
TAX1BP1	“down-regulates activity”	TRAF3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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
TICAM1, RIP1-mediated IKK complex recruitment	7	52.6×	2e-09
RIP-mediated NFkB activation via ZBP1	6	50.4×	4e-08
TNF signaling	9	47.6×	2e-11
Regulation of NF-kappa B signaling	6	47.6×	6e-08
Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7	5	47.6×	1e-06
TNFR1-induced NF-kappa-B signaling pathway	11	46.2×	1e-13
TRAF6 mediated NF-kB activation	8	45.7×	5e-10
TNFR1-induced proapoptotic signaling	8	43.9×	5e-10

GO biological processes:

GO term	Partners	Fold	FDR
canonical NF-kappaB signal transduction	16	59.2×	2e-22
positive regulation of interferon-alpha production	9	58.9×	6e-12
MyD88-dependent toll-like receptor signaling pathway	6	56.7×	6e-08
toll-like receptor 3 signaling pathway	5	56.7×	1e-06
cytoplasmic pattern recognition receptor signaling pathway	6	53.8×	8e-08
non-canonical NF-kappaB signal transduction	6	51.1×	1e-07
interleukin-1-mediated signaling pathway	5	40.5×	5e-06
positive regulation of interferon-beta production	9	35.6×	6e-10

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — PCM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	0
Uncertain significance	177
Likely benign	188
Benign	22

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
2445226	NM_145725.3(TRAF3):c.1458del (p.Pro487fs)	Pathogenic
3238823	NM_145725.3(TRAF3):c.1032G>A (p.Trp344Ter)	Pathogenic
3731305	R338W	Pathogenic
3731306	NM_145725.3(TRAF3):c.1275C>G (p.Tyr425Ter)	Pathogenic
3731307	TRAF3, 1-BP DEL, 1066G	Pathogenic
3731308	NM_145725.3(TRAF3):c.339_340insTAGA (p.Gln114Ter)	Pathogenic
3731309	Q407*	Pathogenic

SpliceAI

2738 predictions. Top by Δscore:

Variant	Effect	Δscore
14:102777674:AGGTA:A	donor_loss	1.0000
14:102777675:GGTAA:G	donor_loss	1.0000
14:102777676:G:GG	donor_gain	1.0000
14:102777676:GT:G	donor_loss	1.0000
14:102777677:T:G	donor_loss	1.0000
14:102870181:ACAGA:A	acceptor_loss	1.0000
14:102870182:CA:C	acceptor_loss	1.0000
14:102870183:A:AG	acceptor_gain	1.0000
14:102870183:A:C	acceptor_loss	1.0000
14:102870184:G:A	acceptor_loss	1.0000
14:102870184:G:GG	acceptor_gain	1.0000
14:102870184:GAA:G	acceptor_gain	1.0000
14:102870184:GAAC:G	acceptor_gain	1.0000
14:102870184:GAACT:G	acceptor_gain	1.0000
14:102870444:GAGG:G	donor_loss	1.0000
14:102870445:AGGTA:A	donor_loss	1.0000
14:102870446:GGTA:G	donor_loss	1.0000
14:102870447:GTAGG:G	donor_loss	1.0000
14:102870448:T:A	donor_loss	1.0000
14:102871964:A:G	donor_gain	1.0000
14:102875616:A:AG	acceptor_gain	1.0000
14:102875617:T:G	acceptor_gain	1.0000
14:102875620:TCA:T	acceptor_loss	1.0000
14:102875622:A:AG	acceptor_gain	1.0000
14:102875622:AG:A	acceptor_gain	1.0000
14:102875622:AGGT:A	acceptor_gain	1.0000
14:102875623:G:GA	acceptor_gain	1.0000
14:102875623:GG:G	acceptor_gain	1.0000
14:102875623:GGT:G	acceptor_gain	1.0000
14:102875623:GGTG:G	acceptor_gain	1.0000

AlphaMissense

3808 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:102870358:T:C	C53R	1.000
14:102870396:G:C	Q65H	1.000
14:102870396:G:T	Q65H	1.000
14:102870407:G:A	G69E	1.000
14:102870418:T:C	C73R	1.000
14:102870419:G:A	C73Y	1.000
14:102875633:G:C	D103H	1.000
14:102875634:A:C	D103A	1.000
14:102875634:A:T	D103V	1.000
14:102875675:T:C	C117R	1.000
14:102886228:T:C	C204R	1.000
14:102889602:T:C	C232R	1.000
14:102889604:T:G	C232W	1.000
14:102889623:T:A	C239S	1.000
14:102889623:T:C	C239R	1.000
14:102889624:G:C	C239S	1.000
14:102905270:G:C	R398P	1.000
14:102905273:T:C	L399P	1.000
14:102905275:G:C	A400P	1.000
14:102905288:T:C	L404P	1.000
14:102905291:G:C	R405P	1.000
14:102905303:T:C	L409P	1.000
14:102905312:C:A	A412D	1.000
14:102905323:G:A	G416R	1.000
14:102905323:G:C	G416R	1.000
14:102905324:G:A	G416E	1.000
14:102905324:G:T	G416V	1.000
14:102905330:T:C	L418P	1.000
14:102905335:T:A	W420R	1.000
14:102905335:T:C	W420R	1.000

dbSNP variants (sampled 300 via entrez): RS1000032655 (14:102790580 G>A), RS1000039420 (14:102861699 A>G), RS1000040253 (14:102822225 G>A,T), RS1000072677 (14:102829972 GATAAA>G), RS1000092332 (14:102822605 C>G,T), RS1000116690 (14:102776011 C>A), RS1000163852 (14:102788752 C>A,G), RS1000196731 (14:102789035 C>T), RS1000203947 (14:102872765 C>A,T), RS1000210935 (14:102791013 T>G), RS1000220004 (14:102827450 C>A), RS1000250112 (14:102816229 A>C,G), RS1000251541 (14:102824394 G>A), RS1000265422 (14:102853204 AT>A,ATT), RS1000267051 (14:102877876 G>A,T)

Disease associations

OMIM: gene MIM:601896 | disease phenotypes: MIM:614849, MIM:621096

GenCC curated gene-disease

Disease	Classification	Inheritance
herpes simplex encephalitis, susceptibility to, 3	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
TRAF3 haploinsufficiency	Moderate	AD

Mondo (4): herpes simplex encephalitis, susceptibility to, 3 (MONDO:0013920), TRAF3 haploinsufficiency (MONDO:0100513), immunodeficiency 132b (MONDO:0976228), ependymoma (MONDO:0016698)

Orphanet (2): Herpes simplex virus encephalitis (Orphanet:1930), Ependymoma (Orphanet:251636)

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000246	Sinusitis
HP:0000403	Recurrent otitis media
HP:0000999	Pyoderma
HP:0001047	Atopic dermatitis
HP:0001250	Seizure
HP:0001259	Coma
HP:0001262	Excessive daytime somnolence
HP:0001347	Hyperreflexia
HP:0001369	Arthritis
HP:0001744	Splenomegaly
HP:0001888	Decreased total lymphocyte count
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002017	Nausea and vomiting
HP:0002028	Chronic diarrhea
HP:0002110	Bronchiectasis
HP:0002133	Status epilepticus
HP:0002167	Abnormal speech pattern
HP:0002181	Cerebral edema
HP:0002205	Recurrent respiratory infections
HP:0002240	Hepatomegaly
HP:0002315	Headache
HP:0002349	Focal aware seizure
HP:0002353	EEG abnormality
HP:0002384	Focal impaired awareness seizure
HP:0002582	Atrophic gastritis
HP:0002586	Peritonitis
HP:0002608	Celiac disease
HP:0002633	Vasculitis

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST000271_2	Brain imaging in schizophrenia (dorsolateral prefrontal cortex interaction)	5.000000e-06
GCST002783_159	Body mass index	3.000000e-07
GCST002783_212	Body mass index	1.000000e-06
GCST002783_564	Body mass index	6.000000e-07
GCST004627_156	Lymphocyte count	5.000000e-15
GCST004632_42	Lymphocyte percentage of white cells	4.000000e-13
GCST005038_88	Allergic disease (asthma, hay fever or eczema)	2.000000e-08
GCST005531_7	Multiple sclerosis	5.000000e-13
GCST005987_1	Albumin-globulin ratio	3.000000e-19
GCST005989_27	Serum total protein levels	3.000000e-20
GCST005990_18	Non-albumin protein levels	2.000000e-24
GCST006000_3	Immunoglobulin measurement (zinc sulfate turbidity test)	1.000000e-09
GCST007050_1	Gallstone disease	1.000000e-07
GCST007400_65	Systemic lupus erythematosus	6.000000e-06
GCST007800_94	Asthma (childhood onset)	3.000000e-11
GCST008129_80	Body mass index	2.000000e-16
GCST008570_1	Composite immunoglobulin trait (IgA x IgG/IgM)	4.000000e-11
GCST009597_127	Multiple sclerosis	2.000000e-15
GCST009718_7	Eczema	5.000000e-10
GCST010042_13	Asthma	1.000000e-09
GCST010118_100	Type 2 diabetes	2.000000e-08
GCST010241_295	Apolipoprotein A1 levels	9.000000e-09
GCST010242_344	HDL cholesterol levels	6.000000e-13
GCST010984_36	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	3.000000e-11
GCST010985_23	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	3.000000e-11
GCST010988_548	Adult body size	2.000000e-15
GCST010989_68	Body size at age 10	4.000000e-09
GCST011096_7	Systemic lupus erythematosus	3.000000e-08
GCST011097_5	Systemic lupus erythematosus	1.000000e-06
GCST011500_6	Gastroesophageal reflux disease, peptic ulcer disease and/or corresponding medications and treatment	4.000000e-08

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005128	albumin:globulin ratio measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004847	age at onset
EFO:0009819	comparative body size at age 10, self-reported
EFO:0009923	Peptic ulcer and gastro-oesophageal reflux disease (GORD) drug use measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0009101	age at first birth measurement
EFO:0005091	monocyte count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004806	Ependymoma	C04.557.465.625.600.380.290; C04.557.470.670.380.290; C04.557.580.625.600.380.290

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance, increases expression	5
Acetaminophen	decreases expression, increases expression	3
Arsenic	increases expression, affects methylation, affects cotreatment, decreases expression, increases abundance	3
Estradiol	increases expression, increases reaction	3
bisphenol A	decreases expression	2
Zoledronic Acid	increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
bisphenol F	increases expression	1
taxifolin	increases expression	1
2-anisidine	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
VX-agent	increases expression	1
beta-lapachone	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
usnic acid	increases expression	1
abrine	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, decreases expression	1
bisphenol S	increases expression	1
ibrutinib	decreases response to substance	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Antigens, Viral	affects binding, decreases reaction	1
Benzene	increases expression	1
Capsaicin	increases expression	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Curcumin	increases expression	1

Cellosaurus cell lines

63 cell lines: 62 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0012	LP-1	Cancer cell line	Female
CVCL_0014	RPMI-8226	Cancer cell line	Male
CVCL_0015	U-266/70	Cancer cell line	Male
CVCL_0016	U-266/84	Cancer cell line	Male
CVCL_0509	RPMI-8226/MR20	Cancer cell line	Male
CVCL_0566	U266B1	Cancer cell line	Male
CVCL_1862	COLO 677	Cancer cell line	Male
CVCL_1996	COLO 775	Cancer cell line	Male
CVCL_2989	KMS-11	Cancer cell line	Female
CVCL_4974	SKO-007	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01096368	PHASE3	COMPLETED	Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma
NCT00003479	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Ependymoma
NCT00520936	PHASE2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01088035	PHASE2	TERMINATED	Carboplatin as a Radiosensitizer in Treating Childhood Ependymoma
NCT01247922	PHASE2	TERMINATED	Single-agent Erlotinib in Patients Previously Treated With Oral Etoposide in Protocol OSI-774-205
NCT01288235	PHASE2	COMPLETED	Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT01295944	PHASE2	COMPLETED	Carboplatin and Bevacizumab for Recurrent Ependymoma
NCT01356290	PHASE2	RECRUITING	Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
NCT01836549	PHASE2	TERMINATED	Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors
NCT02125786	PHASE2	ACTIVE_NOT_RECRUITING	A Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
NCT02689336	PHASE2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT03095248	PHASE2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03173950	PHASE2	COMPLETED	Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers
NCT03194906	PHASE2	COMPLETED	Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT03727841	PHASE2	TERMINATED	Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma
NCT04049669	PHASE2	ACTIVE_NOT_RECRUITING	Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04374305	PHASE2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04743661	PHASE2	ACTIVE_NOT_RECRUITING	131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma
NCT06804655	PHASE2	NOT_YET_RECRUITING	Pharmacoscopy for Patients With Refractory Primary Brain Tumors
NCT07424092	PHASE2	RECRUITING	Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors
NCT00634231	PHASE1	COMPLETED	A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors
NCT00994071	PHASE1	COMPLETED	A Phase I Study of ABT-888, an Oral Inhibitor of Poly(ADP-ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors
NCT01171469	PHASE1	COMPLETED	Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor
NCT01331135	PHASE1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT01498783	PHASE1	COMPLETED	Phase I Study of 5-Fluorouracil in Children and Young Adults With Recurrent Ependymoma