TRAF5

Summary

TRAF5 (TNF receptor associated factor 5, HGNC:12035) is a protein-coding gene on chromosome 1q32.3, encoding TNF receptor-associated factor 5 (O00463). Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases.

The scaffold protein encoded by this gene is a member of the tumor necrosis factor receptor-associated factor (TRAF) protein family and contains a meprin and TRAF homology (MATH) domain, a RING-type zinc finger, and two TRAF-type zinc fingers. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein is one of the components of a multiple protein complex which binds to tumor necrosis factor (TNF) receptor cytoplasmic domains and mediates TNF-induced activation. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7188 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 93 total — 1 likely-pathogenic
• MANE Select transcript: NM_001033910

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12035
Approved symbol	TRAF5
Name	TNF receptor associated factor 5
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Aliases	RNF84
Ensembl gene	ENSG00000082512
Ensembl biotype	protein_coding
OMIM	602356
Entrez	7188

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 14 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000261464, ENST00000336184, ENST00000367004, ENST00000462410, ENST00000473385, ENST00000488428, ENST00000494355, ENST00000891548, ENST00000891549, ENST00000891550, ENST00000891551, ENST00000891552, ENST00000939500, ENST00000939501, ENST00000942797, ENST00000942798, ENST00000942799, ENST00000942800

RefSeq mRNA: 4 — MANE Select: NM_001033910 NM_001033910, NM_001319207, NM_004619, NM_145759

CCDS: CCDS1497

Canonical transcript exons

ENST00000261464 — 11 exons

Exon	Start	End
ENSE00000960280	211359912	211360076
ENSE00000960284	211365376	211365468
ENSE00001010369	211369452	211369592
ENSE00001844109	211326833	211326889
ENSE00001941062	211372128	211374946
ENSE00003484184	211353239	211353457
ENSE00003558079	211360702	211360779
ENSE00003583931	211361088	211361162
ENSE00003627071	211354410	211354467
ENSE00003649957	211356367	211356468
ENSE00003683199	211371302	211371470

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 96.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.9065 / max 421.6764, expressed in 1682 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8421	11.4846	1651
8422	0.9643	445
8418	0.2837	144
8419	0.1398	45
8420	0.0340	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	96.19	gold quality
body of pancreas	UBERON:0001150	94.77	gold quality
blood vessel layer	UBERON:0004797	94.65	gold quality
superficial temporal artery	UBERON:0001614	93.92	gold quality
lymph node	UBERON:0000029	93.72	gold quality
mucosa of stomach	UBERON:0001199	93.50	gold quality
ascending aorta	UBERON:0001496	93.43	gold quality
thoracic aorta	UBERON:0001515	93.38	gold quality
right coronary artery	UBERON:0001625	93.35	gold quality
left uterine tube	UBERON:0001303	93.08	gold quality
descending thoracic aorta	UBERON:0002345	92.92	gold quality
choroid plexus epithelium	UBERON:0003911	92.87	gold quality
vermiform appendix	UBERON:0001154	92.71	gold quality
aorta	UBERON:0000947	92.37	gold quality
body of uterus	UBERON:0009853	92.25	gold quality
myometrium	UBERON:0001296	91.95	gold quality
tibial artery	UBERON:0007610	91.64	gold quality
popliteal artery	UBERON:0002250	91.63	gold quality
caecum	UBERON:0001153	91.49	gold quality
spleen	UBERON:0002106	91.48	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.19	gold quality
left coronary artery	UBERON:0001626	91.16	gold quality
coronary artery	UBERON:0001621	91.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.78	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.40	gold quality
seminal vesicle	UBERON:0000998	90.37	gold quality
lower esophagus	UBERON:0013473	90.37	gold quality
epithelium of nasopharynx	UBERON:0001951	90.30	gold quality
cardia of stomach	UBERON:0001162	90.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	22.56
E-ANND-3	yes	13.95
E-MTAB-7381	no	617.54
E-GEOD-83139	no	2.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB1, REL

miRNA regulators (miRDB)

83 targeting TRAF5, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-1273H-3P	99.29	67.55	980

Literature-anchored findings (GeneRIF, showing 29)

• TRAF5 has a role in TNF-alpha induced IKK phosphorylation of NF-kappaB p65 (PMID:12842894)
• TRAF3 specifically blocked the NF-kappaB activation via TRAF2/5. (PMID:15708970)
• These findings provide evidence for the association of an SNP upstream of a strong candidate RA susceptibility gene, TRAF5. (PMID:17277003)
• Resutls indicate that TRAF5 may be a key molecule in the innate response against viral infection. (PMID:20161788)
• Numbl interacted with tumor necrosis factor receptor-associated factor 5, which signals upstream and is required for the activation of NF-kappaB, and committed it to proteasomal degradation by promoting K48-linked polyubiquitination of TRAF5 (PMID:22593207)
• TRAF3 and TRAF5 are overexpressed in inflammatory bowel disease (PMID:23329887)
• Data indicate that in monocyte- derived macrophages (MDMs) acutely infected with HIV-1 and treated with HCV rCore and HIV-1 rNef, the HIV-1 replication depends on an upstream signal mediated through TRAF2, TRAF5 and TRAF6. (PMID:23774506)
• Data indicate that TNF receptor-associated factor 5 (TRAF5) gene is involved in the development of acute anterior uveitis (AAU) and pediatric uveitis. (PMID:24020968)
• This study provides evidence that TRAF5 and TRAF3IP2 genes are involved in the development of Behcet’s disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome. (PMID:24416204)
• findings reveal a direct link between TRAF5-mediated ubiquitination and RORgammat protein regulation (PMID:26453305)
• RIG-I-like receptor mediated antiviral innate immune responses in the lower respiratory tract involves TRAF3 and TRAF5 signaling. (PMID:26454171)
• Study presents the characterization of the peptide binding preferences of TRAFs 2, 3, and 5 using deep mutational scanning. The three TRAF proteins demonstrated different preferences for binding to members of the CD40 library, and three peptides from that library individually showed striking differences in affinity for the three TRAFs. (PMID:26779844)
• These findings indicate that miR-26b might influence TRAF5-MAPK signaling pathways to facilitate the malignant progression of melanoma cells. (PMID:26872428)
• High TRAF5 expression is associated with colorectal cancer. (PMID:29328486)
• The study highlights the importance of miR-135a-5p and TRAF5 in gliomagenesis and progression and implies their potential prognostic and therapeutic values in malignant glioma. (PMID:30312580)
• These findings suggest that upregulation of miR-29b-3p could protect cardiomyocytes against hypoxia-induced injury through downregulation of TRAF5. (PMID:31011336)
• miR-141-3p inhibited the proliferation, migration, and invasion via directly targeting tumor necrosis factor receptor-associated factor 5 (TRAF5). (PMID:31078266)
• LINC00467 promotes cell proliferation and metastasis by binding with IGF2BP3 to enhance the mRNA stability of TRAF5 in hepatocellular carcinoma. (PMID:31656043)
• TRAF5 acts as a positive regulator of plasmacytoid DCs differentiation from bone marrow progenitors. (PMID:31668809)
• Overexpression of miRNA-410-3p protects hypoxia-induced cardiomyocyte injury via targeting TRAF5. (PMID:31696495)
• miR-141-3p and TRAF5 Network Contributes to the Progression of T-Cell Acute Lymphoblastic Leukemia. (PMID:31722554)
• TRAF5 promotes the occurrence and development of colon cancer via the activation of PI3K/AKT/NF-kappaB signaling pathways. (PMID:32911926)
• Down-regulated HDAC3 elevates microRNA-495-3p to restrain epithelial-mesenchymal transition and oncogenicity of melanoma cells via reducing TRAF5. (PMID:33048450)
• Tumor-Associated Macrophages Promote Oxaliplatin Resistance via METTL3-Mediated m(6)A of TRAF5 and Necroptosis in Colorectal Cancer. (PMID:33555197)
• Single nucleotide polymorphisms of TRAF2 and TRAF5 gene in ankylosing spondylitis: a case-control study. (PMID:33997937)
• Association of methylation level and transcript level in TRAF5 gene with ankylosing spondylitis: a case-control study. (PMID:34021268)
• LncRNA HCG18 upregulates TRAF4/TRAF5 to facilitate proliferation, migration and EMT of epithelial ovarian cancer by targeting miR-29a/b. (PMID:34983361)
• Silencing of TRAF5 enhances necroptosis in hepatocellular carcinoma by inhibiting LTBR-mediated NF-kappaB signaling. (PMID:37366426)
• Tumor necrosis factor receptor-associated factor 5 protects against intimal hyperplasia by regulation of macrophage polarization via directly targeting PPARgamma. (PMID:38642079)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Traf5	ENSMUSG00000026637
rattus_norvegicus	Traf5	ENSRNOG00000047957
caenorhabditis_elegans		WBGENE00006612
caenorhabditis_elegans	trf-2	WBGENE00022454

Paralogs (5): TRAF1 (ENSG00000056558), TRAF4 (ENSG00000076604), TRAF2 (ENSG00000127191), TRAF3 (ENSG00000131323), TRAF6 (ENSG00000175104)

Protein

Protein identifiers

TNF receptor-associated factor 5 — O00463 (reviewed: O00463)

Alternative names: RING finger protein 84

All UniProt accessions (1): O00463

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. Mediates activation of NF-kappa-B and probably JNK. Seems to be involved in apoptosis. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR.

Subunit / interactions. Homotrimer. Heteromer with TRAF3. Associates with TNFRSF5/CD40 through interaction with TRAF3. Associates with LTBR/TNFRSF3, TNFRSF4, TNFRSF8/CD30, TNFRSF11A/RANK, TNFRSF13B/TACI, TNFRSF14, TNFRSF17, TNFRSF19/TROY, RIPK2, MAP3K14, MAP3K5, and TRAF and TNF receptor associated protein TDP2. Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain).

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon, and peripheral blood.

Post-translational modifications. Ubiquitinated at Lys-318 by the SCF(FBXL2) complex, leading to its degradation by the proteasome.

Domain organisation. The MATH/TRAF domain binds to receptor cytoplasmic domains.

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

Isoforms (3)

UniProt ID	Names	Canonical?
O00463-1	1	yes
O00463-2	2
O00463-3	3

RefSeq proteins (4): NP_001029082, NP_001306136, NP_004610, NP_665702 (=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
IPR027130	TRAF5_C3HC3D_RING-HC_finger	Domain
IPR049342	TRAF1-6_MATH_dom	Domain
IPR049440	TRAF3/5_RING	Domain

Pfam: PF02176, PF21355, PF21363

UniProt features (30 total): helix 8, strand 5, sequence variant 4, turn 3, zinc finger region 3, splice variant 2, chain 1, domain 1, region of interest 1, coiled-coil region 1, cross-link 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7L3L	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00463-F1	87.11	0.66

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 (1): 318

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 329 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, BASSO_HAIRY_CELL_LEUKEMIA_DN, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, MODULE_205, ONKEN_UVEAL_MELANOMA_UP, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP

GO Biological Process (13): apoptotic process (GO:0006915), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), positive regulation of cell population proliferation (GO:0008284), signal transduction involved in regulation of gene expression (GO:0023019), CD40 signaling pathway (GO:0023035), tumor necrosis factor-mediated signaling pathway (GO:0033209), regulation of apoptotic process (GO:0042981), regulation of canonical NF-kappaB signal transduction (GO:0043122), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), mRNA stabilization (GO:0048255), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), interleukin-17-mediated signaling pathway (GO:0097400)

GO Molecular Function (9): 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), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), cytoplasmic side of plasma membrane (GO:0009898), CD40 receptor complex (GO:0035631)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
cytokine-mediated signaling pathway	2
canonical NF-kappaB signal transduction	2
cellular anatomical structure	2
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
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of gene expression	1
cell surface receptor signaling pathway	1
cellular response to tumor necrosis factor	1
apoptotic process	1
regulation of programmed cell death	1
regulation of intracellular signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
cellular response to interleukin-17	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
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1

Protein interactions and networks

STRING

1508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAF5	TRADD	Q15628	996
TRAF5	RIPK1	Q13546	992
TRAF5	TNFRSF1A	P19438	991
TRAF5	BIRC2	Q13490	991
TRAF5	BIRC3	Q13489	977
TRAF5	TRAF6	Q9Y4K3	975
TRAF5	TRAF2	Q12933	970
TRAF5	TRAF3	Q13114	960
TRAF5	TNFRSF8	P28908	941
TRAF5	CD40	P25942	906
TRAF5	FADD	Q13158	906
TRAF5	MAVS	Q7Z434	884
TRAF5	LTBR	P36941	863
TRAF5	TNFRSF12A	Q9NP84	861
TRAF5	TNFRSF14	Q92956	820

IntAct

206 interactions, top by confidence:

A	B	Type	Score
TRAF5	TRAF6	psi-mi:“MI:0915”(physical association)	0.880
TRAF6	TRAF5	psi-mi:“MI:0915”(physical association)	0.880
TRAF5	NMI	psi-mi:“MI:0915”(physical association)	0.840
NMI	TRAF5	psi-mi:“MI:0915”(physical association)	0.840
TRAF5	SDCBP	psi-mi:“MI:0915”(physical association)	0.790
SDCBP	TRAF5	psi-mi:“MI:0915”(physical association)	0.790
TRAF5	TRAF5	psi-mi:“MI:0915”(physical association)	0.740
HOMER1	TRAF5	psi-mi:“MI:0914”(association)	0.740
FBXO28	TRAF5	psi-mi:“MI:0914”(association)	0.740
TRAF5	FBXO28	psi-mi:“MI:0915”(physical association)	0.740
TRAF5	HOMER1	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (194): ELAVL1 (Affinity Capture-Western), TRAF5 (Two-hybrid), TRAF5 (Two-hybrid), TRAF5 (Two-hybrid), TRAF5 (Two-hybrid), TRAF5 (Two-hybrid), TRAF6 (Two-hybrid), NMI (Two-hybrid), ENOX2 (Two-hybrid), GORASP2 (Two-hybrid), ZFAND6 (Two-hybrid), THAP1 (Two-hybrid), CCDC184 (Two-hybrid), TRAF5 (Affinity Capture-Western), TRAF5 (Affinity Capture-MS)

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: O00463, P39428, P39429, P68907, P70191, Q12933, Q13077, Q13114, Q60803, Q69ZS0, Q9UPQ7, B5DF45, B6CJY4, B6CJY5, P70196, Q28DL4, Q3MV19, Q3ZCC3, Q61382, Q6DJN2, Q6IWL4, Q9BUZ4, P28825, P28826, Q16820, Q61847, A0A140LI67, A0A1L8FG46, A0A1L8FM16, A0A8C0TYJ0, A7XUJ6, E7FDW2, F1MAD2, G2Q0E2, O14907, O14910, O60106, O88951, O88952, P31007

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TRADD	up-regulates	TRAF5	binding
TNFRSF14	“up-regulates activity”	TRAF5	binding
Ub:E2	“up-regulates activity”	TRAF5	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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
SUMOylation of ubiquitinylation proteins	5	33.3×	9e-05
TNFR2 non-canonical NF-kB pathway	5	20.6×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
tumor necrosis factor-mediated signaling pathway	6	32.5×	9e-06
protein K63-linked ubiquitination	6	26.3×	2e-05
positive regulation of canonical NF-kappaB signal transduction	8	9.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	77
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
800316	NM_001033910.3(TRAF5):c.1254_1257del (p.Glu419fs)	Likely pathogenic

SpliceAI

2129 predictions. Top by Δscore:

Variant	Effect	Δscore
1:211353237:A:AG	acceptor_gain	1.0000
1:211353237:AGAAT:A	acceptor_gain	1.0000
1:211353238:G:GG	acceptor_gain	1.0000
1:211353238:GA:G	acceptor_gain	1.0000
1:211353238:GAATG:G	acceptor_gain	1.0000
1:211353458:G:C	donor_loss	1.0000
1:211353459:T:A	donor_loss	1.0000
1:211369450:A:AC	acceptor_loss	1.0000
1:211369450:A:AG	acceptor_gain	1.0000
1:211369451:G:GA	acceptor_gain	1.0000
1:211369451:GA:G	acceptor_gain	1.0000
1:211369451:GAT:G	acceptor_gain	1.0000
1:211369451:GATT:G	acceptor_gain	1.0000
1:211369451:GATTT:G	acceptor_gain	1.0000
1:211369589:CCAGG:C	donor_loss	1.0000
1:211369593:G:GA	donor_loss	1.0000
1:211369593:G:GG	donor_gain	1.0000
1:211369594:T:G	donor_loss	1.0000
1:211371294:A:AG	acceptor_gain	1.0000
1:211372126:A:AG	acceptor_gain	1.0000
1:211372127:G:GG	acceptor_gain	1.0000
1:211372127:GCC:G	acceptor_gain	1.0000
1:211326890:G:GG	donor_gain	0.9900
1:211327707:C:G	donor_gain	0.9900
1:211353227:T:A	acceptor_gain	0.9900
1:211353234:TGCA:T	acceptor_loss	0.9900
1:211353235:GCAG:G	acceptor_loss	0.9900
1:211353236:CAG:C	acceptor_loss	0.9900
1:211353237:AG:A	acceptor_loss	0.9900
1:211353238:GAAT:G	acceptor_gain	0.9900

AlphaMissense

3725 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:211354432:T:C	C81R	0.999
1:211356376:G:C	D96H	0.999
1:211356377:A:C	D96A	0.999
1:211372250:T:A	W408R	0.999
1:211372250:T:C	W408R	0.999
1:211372376:G:T	G450W	0.999
1:211372377:G:A	G450E	0.999
1:211372377:G:T	G450V	0.999
1:211372454:T:A	W476R	0.999
1:211372454:T:C	W476R	0.999
1:211372456:G:C	W476C	0.999
1:211372456:G:T	W476C	0.999
1:211353372:T:C	C45R	0.998
1:211353410:G:C	Q57H	0.998
1:211353410:G:T	Q57H	0.998
1:211356370:T:C	F94L	0.998
1:211356372:T:A	F94L	0.998
1:211356372:T:G	F94L	0.998
1:211356377:A:T	D96V	0.998
1:211356393:A:C	R101S	0.998
1:211356393:A:T	R101S	0.998
1:211372316:A:C	S430R	0.998
1:211372318:C:A	S430R	0.998
1:211372318:C:G	S430R	0.998
1:211372359:C:A	A444D	0.998
1:211372376:G:A	G450R	0.998
1:211372376:G:C	G450R	0.998
1:211372406:T:C	S460P	0.998
1:211372587:G:A	G520D	0.998
1:211353372:T:A	C45S	0.997

dbSNP variants (sampled 300 via entrez): RS1000128516 (1:211345365 C>A,G), RS1000156736 (1:211354079 C>T), RS1000194738 (1:211350214 CTTTCT>C), RS1000282282 (1:211374230 C>T), RS1000344900 (1:211330769 A>G), RS1000352847 (1:211359733 C>G,T), RS1000365133 (1:211367027 G>A), RS1000454863 (1:211340562 G>A), RS1000590063 (1:211340389 A>G), RS1000691394 (1:211362741 A>G), RS1000767203 (1:211355726 T>C), RS1000854590 (1:211354085 C>T), RS1001018783 (1:211331067 G>A), RS1001041698 (1:211347313 C>T), RS1001116993 (1:211324957 A>C,G)

Disease associations

OMIM: gene MIM:602356 | disease phenotypes: MIM:254500

GenCC curated gene-disease

Mondo (1): plasma cell myeloma (MONDO:0009693)

Orphanet (2): Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009524_12	Household income (MTAG)	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009695	household income

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
Tretinoin	decreases expression	3
(+)-JQ1 compound	decreases expression	2
Valproic Acid	decreases methylation, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
2-anisidine	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
beta-lapachone	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
tamibarotene	decreases expression	1
glycidamide	decreases expression	1
usnic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, decreases expression	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Estradiol	affects expression	1
Fluorides	affects cotreatment, decreases expression	1
Folic Acid	affects cotreatment, increases expression	1

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2JH	Abcam HeLa TRAF5 KO	Cancer cell line	Female
CVCL_D8D0	Ubigene A-549 TRAF5 KO	Cancer cell line	Male
CVCL_D8XN	Ubigene HCT 116 TRAF5 KO	Cancer cell line	Male
CVCL_D9UV	Ubigene HEK293 TRAF5 KO	Transformed cell line	Female
CVCL_E0S2	Ubigene HeLa TRAF5 KO	Cancer cell line	Female
CVCL_TT62	HAP1 TRAF5 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	PHASE4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	PHASE4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	PHASE4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	PHASE4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	PHASE4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	PHASE4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	PHASE4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	PHASE4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	PHASE4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	PHASE4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	PHASE4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	PHASE4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	PHASE4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	PHASE4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	PHASE4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	PHASE4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	PHASE4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	PHASE4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	PHASE4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	PHASE4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	PHASE4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	PHASE4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	PHASE4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	PHASE4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	PHASE4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	PHASE4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	PHASE4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05855122	PHASE4	UNKNOWN	Safety and ASCT-related Symptom Burden Optimization of Tocilizumab in ASCT Following HD Melphalan Conditioning for Multiple Myeloma Patients
NCT05944783	PHASE4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg
NCT06057402	PHASE4	RECRUITING	Elranatamab Post Trial Access Study for Participants With Multiple Myeloma (MM)
NCT06251076	PHASE4	RECRUITING	Plan Development for Giving Teclistamab in the Outpatient Setting