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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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TRAF7
TNF receptor associated factor 7
Chromosome 16 Β· 16p13.3
NCBI Gene: 84231Ensembl: ENSG00000131653.15HGNC: HGNC:20456UniProt: B3KQY7
85PubMed Papers
21Diseases
0Drugs
19Pathogenic Variants
FUNCTIONAL ROLE
ApoptosisTranscription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of apoptotic signaling pathwayubiquitin-protein transferase activityprotein bindingubiquitin ligase complexcardiac, facial, and digital anomalies with developmental delayTRAF7-associated heart defect-digital anomalies-facial dysmorphism-motor and speech delay syndromeGlobal developmental delaymeningioma
✦AI Summary

TRAF7 (TNF receptor-associated factor 7) is an E3 ubiquitin and SUMO-protein ligase with critical roles in innate immunity, inflammation, and apoptosis 1. It potentiates MAP3K3-mediated activation of transcriptional regulators JUN/AP1 and DDIT3, while negatively regulating RLR-mediated innate immunity by promoting Lys-48-linked ubiquitination of TBK1 to suppress antiviral responses 2. TRAF7 also promotes Lys-29-linked polyubiquitination of NEMO/IKBKG and RELA, targeting them to lysosomal degradation and reducing NF-ΞΊB transcriptional activity 3. Mechanistically, TRAF7 interacts with KLF4 to regulate cellular senescence and cell cycle arrest 4. Clinically, TRAF7 mutations represent a major meningioma driver, occurring in nearly 25% of non-NF2 meningiomas 5. These mutations typically co-occur with KLF4(K409Q) or AKT1(E17K) and characterize benign tumors with chr16 stability originating from the medial skull base 5. High TRAF7 expression correlates with glioma recurrence and poor overall survival, making it a potential therapeutic target 4. Additionally, inherited TRAF7 mutations cause congenital cardiac and craniofacial defects through disruption of TRAF7-IFT57 interactions and cilia degradation 6, reflecting shared developmental origins from neural crest tissue.

Sources cited
1
TRAF7 is an E3 ubiquitin and SUMO-protein ligase involved in innate immunity, inflammation, and apoptosis
PMID: 15001576
2
TRAF7 negatively regulates RLR-mediated innate immunity by promoting Lys-48-linked ubiquitination of TBK1
PMID: 37086853
3
TRAF7 promotes Lys-29-linked polyubiquitination of NEMO/IKBKG and RELA, reducing NF-ΞΊB transcriptional activity
PMID: 21518757
4
TRAF7 knockdown induces cellular senescence and cell cycle arrest; high TRAF7 expression associates with glioma recurrence and poor survival
PMID: 40181456
5
TRAF7 mutations occur in nearly 25% of non-NF2 meningiomas, typically co-occurring with KLF4 or AKT1 mutations, characterizing benign skull base tumors
PMID: 23348505
6
Inherited TRAF7 mutations cause congenital cardiac and craniofacial defects through disruption of TRAF7-IFT57 interactions and cilia degradation
PMID: 37043537
Disease Associationsβ“˜21
cardiac, facial, and digital anomalies with developmental delayOpen Targets
0.78Strong
TRAF7-associated heart defect-digital anomalies-facial dysmorphism-motor and speech delay syndromeOpen Targets
0.50Moderate
Global developmental delayOpen Targets
0.45Moderate
meningiomaOpen Targets
0.42Moderate
Abnormal digit morphologyOpen Targets
0.42Moderate
Abnormal heart morphologyOpen Targets
0.42Moderate
Abnormality of limbsOpen Targets
0.42Moderate
genetic disorderOpen Targets
0.41Moderate
craniosynostosisOpen Targets
0.37Weak
Peritoneal MesotheliomaOpen Targets
0.37Weak
Chordoid MeningiomaOpen Targets
0.37Weak
Secretory MeningiomaOpen Targets
0.37Weak
Meningothelial MeningiomaOpen Targets
0.37Weak
Transitional MeningiomaOpen Targets
0.37Weak
Atypical MeningiomaOpen Targets
0.37Weak
gastric carcinomaOpen Targets
0.37Weak
Peritoneal Well Differentiated Papillary MesotheliomaOpen Targets
0.37Weak
Psammomatous MeningiomaOpen Targets
0.37Weak
skin basal cell carcinomaOpen Targets
0.37Weak
superficial spreading melanomaOpen Targets
0.37Weak
Cardiac, facial, and digital anomalies with developmental delayUniProt
Pathogenic Variants19
NM_032271.3(TRAF7):c.1204C>G (p.Leu402Val)Pathogenic
not provided|Cardiac, facial, and digital anomalies with developmental delay
β˜…β˜…β˜†β˜†2026β†’ Residue 402
NM_032271.3(TRAF7):c.1964G>A (p.Arg655Gln)Pathogenic
Cardiac, facial, and digital anomalies with developmental delay|Inborn genetic diseases|not provided|TRAF7-associated heart defect-digital anomalies-facial dysmorphism-motor and speech delay syndrome|TRAF7-related syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 655
NM_032271.3(TRAF7):c.1570C>T (p.Arg524Trp)Pathogenic
TRAF7-related disorder|not provided|Cardiac, facial, and digital anomalies with developmental delay
β˜…β˜…β˜†β˜†2025β†’ Residue 524
NM_032271.3(TRAF7):c.1886G>A (p.Ser629Asn)Pathogenic
Cardiac, facial, and digital anomalies with developmental delay|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 629
NM_032271.3(TRAF7):c.1873C>G (p.Leu625Val)Pathogenic
See cases|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 625
NM_032271.3(TRAF7):c.1673C>T (p.Ser558Phe)Pathogenic
not provided|Cardiac, facial, and digital anomalies with developmental delay
β˜…β˜…β˜†β˜†2020β†’ Residue 558
NM_032271.3(TRAF7):c.1306G>A (p.Glu436Lys)Likely pathogenic
Cardiac, facial, and digital anomalies with developmental delay
β˜…β˜†β˜†β˜†2025β†’ Residue 436
NM_032271.3(TRAF7):c.1958G>T (p.Arg653Leu)Likely pathogenic
Cardiac, facial, and digital anomalies with developmental delay
β˜…β˜†β˜†β˜†2025β†’ Residue 653
NM_032271.3(TRAF7):c.1899G>A (p.Met633Ile)Likely pathogenic
Cardiac, facial, and digital anomalies with developmental delay
β˜…β˜†β˜†β˜†2025β†’ Residue 633
NM_032271.3(TRAF7):c.1571G>A (p.Arg524Gln)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 524
NM_032271.3(TRAF7):c.1936G>A (p.Val646Ile)Pathogenic
Cardiac, facial, and digital anomalies with developmental delay
β˜…β˜†β˜†β˜†2024β†’ Residue 646
NM_032271.3(TRAF7):c.1553G>T (p.Gly518Val)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 518
NM_032271.3(TRAF7):c.1850T>C (p.Phe617Ser)Likely pathogenic
TRAF7-related disorder
β˜…β˜†β˜†β˜†2024β†’ Residue 617
NM_032271.3(TRAF7):c.1124G>A (p.Gly375Asp)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 375
NM_032271.3(TRAF7):c.1783C>G (p.Leu595Val)Likely pathogenic
Cardiac, facial, and digital anomalies with developmental delay
β˜…β˜†β˜†β˜†2021β†’ Residue 595
NM_032271.3(TRAF7):c.1273A>T (p.Thr425Ser)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2019β†’ Residue 425
NM_032271.3(TRAF7):c.1111C>G (p.Arg371Gly)Pathogenic
Cardiac, facial, and digital anomalies with developmental delay
β˜†β˜†β˜†β˜†2018β†’ Residue 371
NM_032271.3(TRAF7):c.1036A>G (p.Lys346Glu)Pathogenic
Cardiac, facial, and digital anomalies with developmental delay
β˜†β˜†β˜†β˜†2018β†’ Residue 346
NM_032271.3(TRAF7):c.1801A>G (p.Thr601Ala)Pathogenic
Cardiac, facial, and digital anomalies with developmental delay
β˜†β˜†β˜†β˜†2018β†’ Residue 601
View on ClinVar β†—
Related Genes
UBA52Protein interaction97%MAP3K3Protein interaction88%MAZProtein interaction79%UBE2E2Protein interaction77%NF2Protein interaction74%CASP12Shared pathway18%
Tissue Expression6 tissues
Liver
100%
Lung
90%
Bone Marrow
76%
Brain
62%
Ovary
57%
Heart
48%
Gene Interaction Network
Click a node to explore
TRAF7UBA52MAP3K3MAZUBE2E2NF2CASP12
PROTEIN STRUCTURE
Preparing viewer…
PDB8IMS Β· 3.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.68LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.53 [0.41–0.68]
RankingsWhere TRAF7 stands among ~20K protein-coding genes
  • #5,646of 20,598
    Most Researched85
  • #2,237of 5,498
    Most Pathogenic Variants19
  • #4,991of 17,882
    Most Constrained (LOEUF)0.68
Genes detectedTRAF7
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Current treatment options for meningioma.
PMID: 29338455
Expert Rev Neurother Β· 2018
1.00
2
DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis.
PMID: 28314689
Lancet Oncol Β· 2017
0.90
3
Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations.
PMID: 26928227
Nat Genet Β· 2016
0.80
4
[Meningioma].
PMID: 37743334
No Shinkei Geka Β· 2023
0.70
5
Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.
PMID: 23348505
Science Β· 2013
0.60