HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TRIM8
tripartite motif containing 8
Chromosome 10 Β· 10q24.32
NCBI Gene: 81603Ensembl: ENSG00000171206.18HGNC: HGNC:15579UniProt: Q9BZR9
69PubMed Papers
21Diseases
0Drugs
20Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
transcription coactivator activityprotein bindinginnate immune responseprotein K63-linked ubiquitinationfocal segmental glomerulosclerosis and neurodevelopmental syndromeSeizureepilepsyGlobal developmental delay
✦AI Summary

TRIM8 is an E3 ubiquitin ligase that functions as a multifaceted regulator of cell survival, differentiation, and innate immunity 1. Mechanistically, TRIM8 promotes Lys-63-linked polyubiquitination of MAP3K7/TAK1 to activate NF-ΞΊB signaling 2, while also modulating STAT3 through negative regulation of PIAS3 3. In innate immunity, TRIM8 negatively regulates TLR3/4-mediated responses by catalyzing Lys-6- and Lys-33-linked polyubiquitination of TICAM1 4. TRIM8 exhibits context-dependent roles in cancer: it suppresses lung cancer metastasis by targeting MYOF for K48-linked degradation 5, yet in Ewing sarcoma, TRIM8 stabilizes the oncogenic EWS/FLI fusion protein 6. Beyond cancer, TRIM8 participates in NAFLD pathogenesis through K48-linked polyubiquitination of HNF4Ξ± within a TRIB3-TRIM8 E3 complex 7. Clinically, de novo TRIM8 truncating variants cause a neuro-renal syndrome characterized by developmental delay, epilepsy, and focal segmental glomerulosclerosis, with variants impairing nuclear body localization 8. TRIM8 also functions as a novel ciliary protein regulating cell cycle progression and mitotic spindle assembly 9. This functional duality across tumor suppression, oncogenic support, and developmental disease underscores TRIM8's complex biological significance 10.

Sources cited
1
TRIM8 is an E3 ubiquitin ligase that functions as a multifaceted regulator of cell survival, differentiation, and innate immunity .
PMID: 27981609
2
Mechanistically, TRIM8 promotes Lys-63-linked polyubiquitination of MAP3K7/TAK1 to activate NF-ΞΊB signaling , while also modulating STAT3 through negative regulation of PIAS3 .
PMID: 22084099
3
Mechanistically, TRIM8 promotes Lys-63-linked polyubiquitination of MAP3K7/TAK1 to activate NF-ΞΊB signaling , while also modulating STAT3 through negative regulation of PIAS3 .
PMID: 20516148
4
In innate immunity, TRIM8 negatively regulates TLR3/4-mediated responses by catalyzing Lys-6- and Lys-33-linked polyubiquitination of TICAM1 .
PMID: 28747347
5
TRIM8 exhibits context-dependent roles in cancer: it suppresses lung cancer metastasis by targeting MYOF for K48-linked degradation , yet in Ewing sarcoma, TRIM8 stabilizes the oncogenic EWS/FLI fusion protein .
PMID: 39934162
6
TRIM8 exhibits context-dependent roles in cancer: it suppresses lung cancer metastasis by targeting MYOF for K48-linked degradation , yet in Ewing sarcoma, TRIM8 stabilizes the oncogenic EWS/FLI fusion protein .
PMID: 34329586
7
Beyond cancer, TRIM8 participates in NAFLD pathogenesis through K48-linked polyubiquitination of HNF4Ξ± within a TRIB3-TRIM8 E3 complex .
PMID: 38237865
8
Clinically, de novo TRIM8 truncating variants cause a neuro-renal syndrome characterized by developmental delay, epilepsy, and focal segmental glomerulosclerosis, with variants impairing nuclear body localization .
PMID: 33508234
9
TRIM8 also functions as a novel ciliary protein regulating cell cycle progression and mitotic spindle assembly .
PMID: 41057298
10
This functional duality across tumor suppression, oncogenic support, and developmental disease underscores TRIM8's complex biological significance .
PMID: 33230447
Disease Associationsβ“˜21
focal segmental glomerulosclerosis and neurodevelopmental syndromeOpen Targets
0.78Strong
SeizureOpen Targets
0.62Moderate
epilepsyOpen Targets
0.46Moderate
Global developmental delayOpen Targets
0.46Moderate
Intellectual disabilityOpen Targets
0.46Moderate
nephrotic syndromeOpen Targets
0.46Moderate
genetic disorderOpen Targets
0.41Moderate
focal segmental glomerulosclerosisOpen Targets
0.41Moderate
Neurodevelopmental delayOpen Targets
0.40Weak
ethylmalonic encephalopathyOpen Targets
0.37Weak
Neurodevelopmental disorderOpen Targets
0.37Weak
early-infantile DEEOpen Targets
0.37Weak
prostate carcinomaOpen Targets
0.25Weak
atrial fibrillationOpen Targets
0.20Weak
pyelonephritisOpen Targets
0.18Weak
prostate cancerOpen Targets
0.14Weak
hearing lossOpen Targets
0.13Weak
major depressive disorderOpen Targets
0.10Weak
neoplasmOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
Focal segmental glomerulosclerosis and neurodevelopmental syndromeUniProt
Pathogenic Variants20
NM_030912.3(TRIM8):c.1240C>T (p.Gln414Ter)Pathogenic
Neurodevelopmental delay;Focal segmental glomerulosclerosis;Seizure|Focal segmental glomerulosclerosis and neurodevelopmental syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 414
NM_030912.3(TRIM8):c.1231C>T (p.Gln411Ter)Pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome|Neurodevelopmental delay;Focal segmental glomerulosclerosis;Seizure|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 411
NM_030912.3(TRIM8):c.1375C>T (p.Gln459Ter)Pathogenic
TRIM8-related epileptic encephalopathy|Focal segmental glomerulosclerosis and neurodevelopmental syndrome|not provided|Inborn genetic diseases|Seizure;Neurodevelopmental delay;Focal segmental glomerulosclerosis
β˜…β˜…β˜†β˜†2024β†’ Residue 459
NM_030912.3(TRIM8):c.1390A>T (p.Lys464Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 464
NM_030912.3(TRIM8):c.1310C>G (p.Ser437Ter)Pathogenic
Seizure
β˜…β˜†β˜†β˜†2024β†’ Residue 437
NM_030912.3(TRIM8):c.1200C>A (p.Tyr400Ter)Pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 400
NM_030912.3(TRIM8):c.1357C>T (p.Gln453Ter)Pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 453
NM_030912.3(TRIM8):c.1474del (p.His492fs)Likely pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 492
NM_030912.3(TRIM8):c.1062del (p.Pro355fs)Likely pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 355
NM_030912.3(TRIM8):c.1120del (p.Ala374fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 374
NM_030912.3(TRIM8):c.1200C>G (p.Tyr400Ter)Likely pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 400
NM_030912.3(TRIM8):c.1267C>T (p.Gln423Ter)Pathogenic
not provided|Neurodevelopmental delay;Focal segmental glomerulosclerosis;Seizure
β˜…β˜†β˜†β˜†2020β†’ Residue 423
NM_030912.3(TRIM8):c.1257C>A (p.Cys419Ter)Pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 419
NM_030912.3(TRIM8):c.1380T>A (p.Tyr460Ter)Pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome|Seizure;Focal segmental glomerulosclerosis;Neurodevelopmental delay
β˜†β˜†β˜†β˜†2021β†’ Residue 460
NM_030912.3(TRIM8):c.1338T>A (p.Tyr446Ter)Pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 446
NM_030912.3(TRIM8):c.1331C>A (p.Ser444Ter)Pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 444
NM_030912.3(TRIM8):c.1198_1220del (p.Tyr400fs)Pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 400
NM_030912.3(TRIM8):c.1163del (p.Phe388fs)Pathogenic
Seizure;Focal segmental glomerulosclerosis;Neurodevelopmental delay|Focal segmental glomerulosclerosis and neurodevelopmental syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 388
NM_030912.3(TRIM8):c.1333C>T (p.Gln445Ter)Pathogenic
Focal segmental glomerulosclerosis and neurodevelopmental syndrome|Seizure;Focal segmental glomerulosclerosis;Neurodevelopmental delay
β˜†β˜†β˜†β˜†2021β†’ Residue 445
NM_030912.3(TRIM8):c.1461C>G (p.Tyr487Ter)Likely pathogenic
Focal segmental glomerulosclerosis;Seizure;Neurodevelopmental delay
β˜†β˜†β˜†β˜†2021β†’ Residue 487
View on ClinVar β†—
Related Genes
SOCS1Protein interaction95%TRAT1Protein interaction79%PIAS3Protein interaction76%MID2Shared pathway55%TRIM5Shared pathway33%TRIM11Shared pathway33%
Tissue Expression6 tissues
Lung
100%
Liver
73%
Heart
64%
Ovary
57%
Bone Marrow
48%
Brain
48%
Gene Interaction Network
Click a node to explore
TRIM8SOCS1TRAT1PIAS3MID2TRIM5TRIM11
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9BZR9
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.29Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.17 [0.10–0.29]
RankingsWhere TRIM8 stands among ~20K protein-coding genes
  • #6,860of 20,598
    Most Researched69
  • #2,194of 5,498
    Most Pathogenic Variants20
  • #1,072of 17,882
    Most Constrained (LOEUF)0.29 Β· top 10%
Genes detectedTRIM8
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4Ξ± stability.
PMID: 38237865
J Hepatol Β· 2024
1.00
2
TRIM8 modulates the EWS/FLI oncoprotein to promote survival in Ewing sarcoma.
PMID: 34329586
Cancer Cell Β· 2021
0.90
3
E3 ligase TRIM8 suppresses lung cancer metastasis by targeting MYOF degradation through K48-linked polyubiquitination.
PMID: 39934162
Cell Death Dis Β· 2025
0.80
4
m6A Modification Promotes EMT and Metastasis of Castration-Resistant Prostate Cancer by Upregulating NFIB.
PMID: 38536119
Cancer Res Β· 2024
0.70
5
Rise of TRIM8: A Molecule of Duality.
PMID: 33230447
Mol Ther Nucleic Acids Β· 2020
0.60