TRAF7

Summary

TRAF7 (TNF receptor associated factor 7, HGNC:20456) is a protein-coding gene on chromosome 16p13.3, encoding E3 ubiquitin-protein ligase TRAF7 (Q6Q0C0). E3 ubiquitin and SUMO-protein ligase that plays a role in different biological processes such as innate immunity, inflammation or apoptosis.

Tumor necrosis factor (TNF; see MIM 191160) receptor-associated factors, such as TRAF7, are signal transducers for members of the TNF receptor superfamily (see MIM 191190). TRAFs are composed of an N-terminal cysteine/histidine-rich region containing zinc RING and/or zinc finger motifs; a coiled-coil (leucine zipper) motif; and a homologous region that defines the TRAF family, the TRAF domain, which is involved in self-association and receptor binding.

Source: NCBI Gene 84231 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 252 total — 7 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 147
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_032271

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20456
Approved symbol	TRAF7
Name	TNF receptor associated factor 7
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	RNF119, DKFZp586I021, MGC7807
Ensembl gene	ENSG00000131653
Ensembl biotype	protein_coding
OMIM	606692
Entrez	84231

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 28 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000326181, ENST00000564067, ENST00000565383, ENST00000567645, ENST00000567653, ENST00000569686, ENST00000570169, ENST00000704452, ENST00000704453, ENST00000910777, ENST00000910778, ENST00000910779, ENST00000910780, ENST00000910781, ENST00000910782, ENST00000910783, ENST00000910784, ENST00000910785, ENST00000910786, ENST00000910787, ENST00000910788, ENST00000910789, ENST00000910790, ENST00000916804, ENST00000916805, ENST00000916806, ENST00000916807, ENST00000916808, ENST00000916809, ENST00000956437, ENST00000956438, ENST00000956439, ENST00000956440

RefSeq mRNA: 1 — MANE Select: NM_032271 NM_032271

CCDS: CCDS10461

Canonical transcript exons

ENST00000326181 — 21 exons

Exon	Start	End
ENSE00000901571	2176049	2176180
ENSE00000901572	2175834	2175953
ENSE00000901573	2175500	2175622
ENSE00000901574	2175301	2175417
ENSE00000901575	2175111	2175150
ENSE00000901579	2173481	2173554
ENSE00000901580	2173182	2173399
ENSE00000901581	2172465	2172599
ENSE00001330985	2176265	2176384
ENSE00001401105	2155782	2155858
ENSE00001429861	2176560	2178129
ENSE00003505871	2173921	2174048
ENSE00003508006	2168077	2168168
ENSE00003518467	2171572	2171605
ENSE00003567315	2170614	2170730
ENSE00003575656	2172191	2172374
ENSE00003586211	2173788	2173836
ENSE00003604655	2174251	2174333
ENSE00003668211	2165879	2165936
ENSE00003673987	2163883	2164001
ENSE00003790187	2171264	2171356

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 97.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.8478 / max 260.1485, expressed in 1819 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152199	67.7655	1819
152201	0.0574	13
152200	0.0249	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.57	gold quality
pancreatic ductal cell	CL:0002079	95.70	gold quality
lower esophagus mucosa	UBERON:0035834	95.06	gold quality
cortical plate	UBERON:0005343	94.60	gold quality
ganglionic eminence	UBERON:0004023	94.57	gold quality
skin of leg	UBERON:0001511	94.29	gold quality
esophagus mucosa	UBERON:0002469	94.25	gold quality
skin of abdomen	UBERON:0001416	94.06	gold quality
mucosa of transverse colon	UBERON:0004991	93.80	gold quality
esophagus	UBERON:0001043	93.74	gold quality
left uterine tube	UBERON:0001303	93.73	gold quality
mucosa of stomach	UBERON:0001199	93.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.51	gold quality
lower esophagus	UBERON:0013473	93.49	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.48	gold quality
body of stomach	UBERON:0001161	93.47	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.36	gold quality
transverse colon	UBERON:0001157	93.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.25	gold quality
gall bladder	UBERON:0002110	93.18	gold quality
minor salivary gland	UBERON:0001830	93.17	gold quality
right lobe of liver	UBERON:0001114	93.16	gold quality
oviduct epithelium	UBERON:0004804	93.06	gold quality
ventricular zone	UBERON:0003053	92.80	gold quality
adenohypophysis	UBERON:0002196	92.75	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.73	gold quality
ectocervix	UBERON:0012249	92.65	gold quality
vermiform appendix	UBERON:0001154	92.53	gold quality
upper lobe of left lung	UBERON:0008952	92.44	gold quality
vagina	UBERON:0000996	92.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting TRAF7, 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-4455	100.00	65.48	1587
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6766-5P	99.68	67.70	2325

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 27)

• TRAF7 potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis (PMID:15001576)
• this study identifies TRAF7 as a NEMO- and p65-interacting molecule and brings important information on the ubiquitination events that control NF-kappaB transcriptional activity. (PMID:21518757)
• TRAF7 is involved in signal transduction pathways that lead either to activation or repression of NF-kappaB transcription factor. (PMID:22105767)
• an important role for TRAF7 in the activation of JNK following TNFalpha stimulation and involvement of this protein in regulating the turnover of c-FLIP (PMID:22219201)
• Downregulation of ubiquitin E3 ligase TNF receptor-associated factor 7 leads to stabilization of p53 in breast cancer. (PMID:23128672)
• Nearly one-fourth of all meningiomas have mutations in TRAF7. (PMID:23348505)
• The findings of this study suggested an essential contribution of combined KLF4 K409Q and TRAF7 mutations in the genesis of secretory meningioma and demonstrate a role for TRAF7 alterations in other non-NF2 meningiomas. (PMID:23404370)
• TRAF7 is a direct target of miR-126 in human umbilical cord vascular endothelial cells. (PMID:25318608)
• TRAF7 mutations icause intraneural perineuriomas. (PMID:28019650)
• these studies demonstrate that adenomatoid tumors of the male and female genital tract are genetically defined by TRAF7 mutation (PMID:29148537)
• The suppression of apoptosis in AML with high expression of miRNA-126 was caused by down-regulating TRAF7 (PMID:29940130)
• Missense mutations in TRAF7 are associated with a multisystem disorder. (PMID:29961569)
• well-differentiated papillary mesothelioma is genetically defined by mutually exclusive mutations in TRAF7 and CDC42 that molecularly distinguish this entity from malignant mesothelioma (PMID:30171198)
• The up-regulation of TRAF7 promoted HCC cell migration and invasion in vivo and in vitro, and TRAF7 knockdown had the opposite effects. Restoration of KLF4 abrogated the motility promotion induced by TRAF7. TRAF7 promotes HCC cell motility through inducing KLF4 protein turnover. (PMID:31730901)
• Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7. (PMID:32376980)
• Sinus pericranii, skull defects, and structural brain anomalies in TRAF7-related disorder. (PMID:32459067)
• New Syndrome Associated with Germline Variants in TRAF7. (PMID:33043583)
• TRAF7 mutations and immunohistochemical study of uterine adenomatoid tumor compared with malignant mesothelioma. (PMID:33667423)
• Long non-coding RNA NEAT1 regulates endothelial functions in subclinical hypothyroidism through miR-126/TRAF7 pathway. (PMID:33677813)
• Loss-of-Function Mutations in TRAF7 and KLF4 Cooperatively Activate RAS-Like GTPase Signaling and Promote Meningioma Development. (PMID:34215617)
• Prenatal diagnosis of a germline variant in TRAF7: Importance of accessibility to prenatal exome sequencing in cases of structural fetal anomalies. (PMID:35684978)
• TRAF7-mutated Fibromyxoid Spindle Cell Tumors Are Associated With an Aggressive Clinical Course and Harbor an Undifferentiated Sarcoma Methylation Signature: A Molecular and Clinicopathologic Study of 3 Cases. (PMID:36395468)
• TRAF7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the KLF2-PFKFB3 axis. (PMID:37003349)
• Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease. (PMID:37043537)
• Novel mosaic TRAF7 likely pathogenic variant in an African American family. (PMID:37067385)
• The Chlamydia trachomatis Inc Tri1 interacts with TRAF7 to displace native TRAF7 interacting partners. (PMID:38814079)
• Expression of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) Candidate Genes EDA2R, PCDH9, and TRAF7 in Normal Human Kidney Development and CAKUT. (PMID:38927638)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	traf7	ENSDARG00000060207
mus_musculus	Traf7	ENSMUSG00000052752
rattus_norvegicus	Traf7	ENSRNOG00000003131

Paralogs (14): WDR54 (ENSG00000005448), FBXW11 (ENSG00000072803), FBXW7 (ENSG00000109670), FBXW9 (ENSG00000132004), FBXO36 (ENSG00000153832), WDR64 (ENSG00000162843), FBXW12 (ENSG00000164049), BTRC (ENSG00000166167), WDR49 (ENSG00000174776), FBXW8 (ENSG00000174989), PAAF1 (ENSG00000175575), WDR86 (ENSG00000187260), FBXO16 (ENSG00000214050), EFCAB8 (ENSG00000215529)

Protein

Protein identifiers

E3 ubiquitin-protein ligase TRAF7 — Q6Q0C0 (reviewed: Q6Q0C0)

Alternative names: RING finger and WD repeat-containing protein 1, RING finger protein 119, RING-type E3 ubiquitin transferase TRAF7, TNF receptor-associated factor 7

All UniProt accessions (5): A0A087WUB0, A0A994J4N1, Q6Q0C0, H3BR17, H3BUP4

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin and SUMO-protein ligase that plays a role in different biological processes such as innate immunity, inflammation or apoptosis. Potentiates MAP3K3-mediated activation of JUN/AP1 and DDIT3 transcriptional regulators. Negatively regulates MYB transcriptional activity by sequestering it to the cytosol via SUMOylation. Plays a role in the phosphorylation of MAPK1 and/or MAPK3, probably via its interaction with MAP3K3. Negatively regulates RLR-mediated innate immunity by promoting ‘Lys-48’-linked ubiquitination of TBK1 through its RING domain to inhibit the cellular antiviral response. Promotes ‘Lys-29’-linked polyubiquitination of NEMO/IKBKG and RELA leading to targeting these two proteins to lysosomal degradative pathways, reducing the transcriptional activity of NF-kappa-B.

Subunit / interactions. Homodimer. Interacts with MAP3K3 and promotes the kinase activity of this enzyme.

Subcellular location. Cytoplasmic vesicle. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed with high levels in skeletal muscle, heart, colon, spleen, kidney, liver and placenta.

Post-translational modifications. Phosphorylated by MAP3K3. Ubiquitinates itself upon phosphorylation.

Disease relevance. Cardiac, facial, and digital anomalies with developmental delay (CAFDADD) [MIM:618164] An autosomal dominant disorder characterized by delayed motor and speech development, developmental regression, congenital heart defects, limb and digital anomalies, and dysmorphic features. Cardiac features include pulmonary stenosis, patent ductus arteriosus, aortic coarctation, valvular defects, hypoplastic left heart, double outlet right ventricle, and conduction abnormalities. Dysmorphic facial features include multiple hair whorls or hairline abnormalities, ptosis, epicanthal folds, and low-set or dysplastic ears. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the WD repeat TRAF7 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6Q0C0-1	1	yes
Q6Q0C0-2	2

RefSeq proteins (1): NP_115647* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001293	Znf_TRAF	Domain
IPR001680	WD40_rpt	Repeat
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR027370	Znf-RING_euk	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400, PF13445

UniProt features (24 total): repeat 7, sequence variant 4, modified residue 3, region of interest 2, compositionally biased region 2, zinc finger region 2, chain 1, splice variant 1, mutagenesis site 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8IMS	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6Q0C0-F1	80.16	0.52

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 (3): 61, 88, 91

Mutagenesis-validated functional residues (1):

Position	Phenotype
131	complete loss of ifn-beta promoter inhibition after viral infection.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-9958825	Activation of STAT3 by cadherin engagement

MSigDB gene sets: 419 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GTTAAAG_MIR302B, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, TGIF_01, GGCAGTG_MIR3243P, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, ATGCTGG_MIR338, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (11): apoptotic process (GO:0006915), protein ubiquitination (GO:0016567), protein K29-linked ubiquitination (GO:0035519), positive regulation of MAPK cascade (GO:0043410), positive regulation of neuron apoptotic process (GO:0043525), regulation of ERK1 and ERK2 cascade (GO:0070372), positive regulation of ubiquitin-dependent protein catabolic process (GO:2000060), positive regulation of apoptotic signaling pathway (GO:2001235), regulation of transcription by RNA polymerase II (GO:0006357), canonical NF-kappaB signal transduction (GO:0007249), positive regulation of protein metabolic process (GO:0051247)

GO Molecular Function (6): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1
Adherens junctions interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic signaling pathway	2
regulation of MAPK cascade	2
positive regulation of apoptotic process	2
programmed cell death	1
execution phase of apoptosis	1
protein modification by small protein conjugation	1
protein polyubiquitination	1
MAPK cascade	1
positive regulation of intracellular signal transduction	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
ERK1 and ERK2 cascade	1
ubiquitin-dependent protein catabolic process	1
positive regulation of protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
positive regulation of signal transduction	1
regulation of apoptotic signaling pathway	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
intracellular signaling cassette	1
positive regulation of macromolecule metabolic process	1
protein metabolic process	1
regulation of protein metabolic process	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cytoplasm	1
intracellular vesicle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAF7	MAP3K3	Q99759	728
TRAF7	NF2	P35240	720
TRAF7	UBE2E2	Q96LR5	660
TRAF7	TRAF1	Q13077	624
TRAF7	TRAF6	Q9Y4K3	617
TRAF7	KLF4	P78338	604
TRAF7	MAP3K7	O43318	592
TRAF7	POLR2A	P24928	580
TRAF7	SMARCB1	Q12824	541
TRAF7	UBA1	P22314	518
TRAF7	SMARCE1	Q969G3	506
TRAF7	UBE3A	P78355	483
TRAF7	NFKB1	P19838	470
TRAF7	PIK3CA	P42336	465
TRAF7	AKT1	P31749	460

IntAct

225 interactions, top by confidence:

A	B	Type	Score
STAM	HGS	psi-mi:“MI:0914”(association)	0.860
MAP2K5	MAPK7	psi-mi:“MI:0914”(association)	0.860
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
RAC1	RAP1GDS1	psi-mi:“MI:0914”(association)	0.800
MAP3K3	TRAF7	psi-mi:“MI:0915”(physical association)	0.750
MAP3K3	TRAF7	psi-mi:“MI:0403”(colocalization)	0.750
FBXO28	TRAF5	psi-mi:“MI:0914”(association)	0.740
PFDN4	PFDN6	psi-mi:“MI:0914”(association)	0.730
RHOA	CTSA	psi-mi:“MI:0914”(association)	0.730
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
TRIM44	CUL2	psi-mi:“MI:0914”(association)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
LIME1	TRAF7	psi-mi:“MI:0915”(physical association)	0.620
SCRIB	TRAF7	psi-mi:“MI:0407”(direct interaction)	0.590
TRAF7	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.590
MAP3K3	TCP1	psi-mi:“MI:0914”(association)	0.560
ZNF764	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
TRIM44	ODAD3	psi-mi:“MI:0914”(association)	0.530
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
DEUP1	HIP1	psi-mi:“MI:0914”(association)	0.530
COMMD10	VPS26C	psi-mi:“MI:0914”(association)	0.530
OIP5	CYTH3	psi-mi:“MI:0914”(association)	0.530
RALYL	CDC40	psi-mi:“MI:0914”(association)	0.530
MMP10	TIMP1	psi-mi:“MI:0914”(association)	0.530
ABRAXAS2	LAMC1	psi-mi:“MI:0914”(association)	0.530

BioGRID (209): TRAF7 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), TRAF7 (Proximity Label-MS), TRAF7 (Affinity Capture-MS), TRAF7 (Proximity Label-MS), TRAF7 (Affinity Capture-MS)

ESM2 similar proteins: A0AUS0, A5DNK9, A8XSW2, A8XXC7, B3NSK1, B4HND9, B4J8H6, B4KRQ4, B4MFM2, B4P7H8, B4QB64, B6K7R8, E9Q4P1, G5EEG7, O16023, O60161, O94394, Q18964, Q1LZ08, Q20059, Q24338, Q25306, Q26458, Q2KIY3, Q2TAF3, Q2TAY7, Q2TBS9, Q3UKJ7, Q5ZMC3, Q5ZME8, Q6C953, Q6NRT3, Q6P4J8, Q6Q0C0, Q759U7, Q76B40, Q7ZVA0, Q8BUB4, Q8IWB7, Q8IZU2

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, A0JN74, A6NGJ6, A6NI03

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
TRAF7	up-regulates	Apoptosis
TRAF7	up-regulates	MAP3K3	binding
TRAF7	up-regulates	Cell_death
Ub:E2	“up-regulates activity”	TRAF7	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 221 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.

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	7	19.6×	6e-05
receptor clustering	6	18.1×	5e-04
protein transport	16	3.4×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — PLMESO.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	8
Uncertain significance	132
Likely benign	51
Benign	10

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1203798	NM_032271.3(TRAF7):c.1673C>T (p.Ser558Phe)	Pathogenic
1327659	NM_032271.3(TRAF7):c.1204C>G (p.Leu402Val)	Pathogenic
3730875	NM_032271.3(TRAF7):c.1571G>A (p.Arg524Gln)	Pathogenic
3765873	NM_032271.3(TRAF7):c.1936G>A (p.Val646Ile)	Pathogenic
587686	NM_032271.3(TRAF7):c.1801A>G (p.Thr601Ala)	Pathogenic
587687	NM_032271.3(TRAF7):c.1036A>G (p.Lys346Glu)	Pathogenic
587688	NM_032271.3(TRAF7):c.1111C>G (p.Arg371Gly)	Pathogenic
1698784	NM_032271.3(TRAF7):c.1783C>G (p.Leu595Val)	Likely pathogenic
2500518	NM_032271.3(TRAF7):c.1124G>A (p.Gly375Asp)	Likely pathogenic
2663925	NM_032271.3(TRAF7):c.1958G>T (p.Arg653Leu)	Likely pathogenic
3393577	NM_032271.3(TRAF7):c.1553G>T (p.Gly518Val)	Likely pathogenic
3773822	NM_032271.3(TRAF7):c.1850T>C (p.Phe617Ser)	Likely pathogenic
4526660	NM_032271.3(TRAF7):c.1899G>A (p.Met633Ile)	Likely pathogenic
4531594	NM_032271.3(TRAF7):c.1306G>A (p.Glu436Lys)	Likely pathogenic
872319	NM_032271.3(TRAF7):c.1273A>T (p.Thr425Ser)	Likely pathogenic

SpliceAI

3625 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2155854:GGCGG:G	donor_gain	1.0000
16:2155855:GCGG:G	donor_gain	1.0000
16:2155855:GCGGG:G	donor_gain	1.0000
16:2155856:CGGGT:C	donor_loss	1.0000
16:2155857:GG:G	donor_gain	1.0000
16:2155858:GG:G	donor_gain	1.0000
16:2155858:GGT:G	donor_loss	1.0000
16:2155859:G:A	donor_loss	1.0000
16:2155860:T:G	donor_loss	1.0000
16:2168071:TTGCA:T	acceptor_loss	1.0000
16:2168072:TGCA:T	acceptor_loss	1.0000
16:2168074:CA:C	acceptor_loss	1.0000
16:2168075:A:AG	acceptor_gain	1.0000
16:2168075:A:AT	acceptor_loss	1.0000
16:2168075:AGCT:A	acceptor_gain	1.0000
16:2168076:G:GA	acceptor_gain	1.0000
16:2168076:GC:G	acceptor_gain	1.0000
16:2168076:GCT:G	acceptor_gain	1.0000
16:2168076:GCTG:G	acceptor_gain	1.0000
16:2168164:GCATG:G	donor_gain	1.0000
16:2168168:GGTA:G	donor_loss	1.0000
16:2168169:G:GG	donor_gain	1.0000
16:2168169:GTAG:G	donor_loss	1.0000
16:2168170:TAG:T	donor_loss	1.0000
16:2171255:T:TA	acceptor_gain	1.0000
16:2171256:G:A	acceptor_gain	1.0000
16:2172190:GA:G	acceptor_gain	1.0000
16:2172190:GAGA:G	acceptor_gain	1.0000
16:2172190:GAGAA:G	acceptor_gain	1.0000
16:2172370:CGGAA:C	donor_gain	1.0000

AlphaMissense

4419 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:2171306:T:C	C131R	1.000
16:2171337:C:A	P141H	1.000
16:2171343:T:A	I143N	1.000
16:2171351:T:C	C146R	1.000
16:2171355:G:A	G147E	1.000
16:2171581:T:C	C151R	1.000
16:2171582:G:A	C151Y	1.000
16:2172196:T:C	C161R	1.000
16:2172237:C:A	N174K	1.000
16:2172237:C:G	N174K	1.000
16:2172242:C:A	A176E	1.000
16:2172277:T:C	C188R	1.000
16:2172343:T:C	C210R	1.000
16:2172481:T:C	C226R	1.000
16:2172482:G:A	C226Y	1.000
16:2172502:T:A	C233S	1.000
16:2172502:T:C	C233R	1.000
16:2172503:G:C	C233S	1.000
16:2172520:T:C	C239R	1.000
16:2172565:T:A	C254S	1.000
16:2172565:T:C	C254R	1.000
16:2172566:G:C	C254S	1.000
16:2172580:T:A	C259S	1.000
16:2172580:T:C	C259R	1.000
16:2172581:G:C	C259S	1.000
16:2172582:C:G	C259W	1.000
16:2173183:T:A	C266S	1.000
16:2173183:T:C	C266R	1.000
16:2173184:G:A	C266Y	1.000
16:2173184:G:C	C266S	1.000

dbSNP variants (sampled 300 via entrez): RS1000083182 (16:2157883 AGCC>A), RS1000131982 (16:2170964 G>A), RS1000372390 (16:2154145 C>G,T), RS1000505285 (16:2155626 T>C), RS1000559626 (16:2171990 G>A,T), RS1000598022 (16:2155808 G>C,T), RS1000632585 (16:2167991 C>G,T), RS1000756349 (16:2159655 G>C), RS1000879318 (16:2171834 CAGTG>C), RS1001025387 (16:2176955 G>C,T), RS1001179705 (16:2162660 C>A), RS1001297202 (16:2171197 G>A,C,T), RS1001405817 (16:2167526 G>A), RS1001470352 (16:2167029 C>T), RS1001589685 (16:2154707 T>C)

Disease associations

OMIM: gene MIM:606692 | disease phenotypes: MIM:618164, MIM:618970

GenCC curated gene-disease

Disease	Classification	Inheritance
cardiac, facial, and digital anomalies with developmental delay	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic complex neurodevelopmental disorder	Definitive	AD

Mondo (2): cardiac, facial, and digital anomalies with developmental delay (MONDO:0032572), cone-rod synaptic disorder syndrome, congenital nonprogressive (MONDO:0033543)

Orphanet (1): TRAF7-associated heart defect-digital anomalies-facial dysmorphism-motor and speech delay syndrome (Orphanet:592570)

HPO phenotypes

147 total (30 of 147 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000023	Inguinal hernia
HP:0000044	Hypogonadotropic hypogonadism
HP:0000141	Amenorrhea
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000414	Bulbous nose
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000474	Thickened nuchal skin fold
HP:0000476	Cystic hygroma
HP:0000486	Strabismus
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000581	Blepharophimosis
HP:0000602	Ophthalmoplegia
HP:0000618	Blindness
HP:0000648	Optic atrophy
HP:0000712	Emotional lability
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000768	Pectus carinatum

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST007270_6	Systolic blood pressure	4.000000e-18
GCST007271_2	Diastolic blood pressure	9.000000e-15
GCST007272_13	Pulse pressure	3.000000e-07
GCST008163_244	Height	7.000000e-07
GCST008163_360	Height	2.000000e-09
GCST90013406_266	Liver enzyme levels (alkaline phosphatase)	1.000000e-34

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance	2
GSK-J4	increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
cupric oxide	decreases expression	1
jinfukang	increases expression, increases reaction	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Cisplatin	increases expression, increases reaction	1
Diazinon	increases methylation	1
Ozone	increases abundance, affects expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases methylation	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A8PJ	SHCMDLi001-A	Induced pluripotent stem cell	Female
CVCL_B2JJ	Abcam HeLa TRAF7 KO	Cancer cell line	Female
CVCL_LC28	UOK276	Cancer cell line	Male
CVCL_TT65	HAP1 TRAF7 (-) 1	Cancer cell line	Male
CVCL_TT66	HAP1 TRAF7 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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