TRIM58

Chr 1

tripartite motif containing 58

Also known as: BIA2

NCBI Gene: 25893ENSG00000162722UniProt: Q8NG06OMIM: 620527

The protein functions as an E3 ubiquitin ligase that regulates dynein motor protein degradation by ubiquitinating dynein intermediate chains, and may participate in erythroblast enucleation through nuclear polarization control. Mutations cause autosomal recessive developmental delay with seizures and dysmorphism. The gene shows very low constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.56
Clinical Summary— TRIM58
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
69 unique Pathogenic / Likely Pathogenic· 88 VUS of 183 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.56LOEUF
pLI 0.000
Z-score -0.08
OE 1.02 (0.68–1.56)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.42Z-score
OE missense 0.92 (0.83–1.03)
219 obs / 237.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.02 (0.68–1.56)
0≤0.351.4
Missense OE0.92 (0.83–1.03)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 15 / 14.7Missense obs/exp: 219 / 237.1Syn Z: -0.76
DN
0.76top 25%
GOF
0.77top 25%
LOF
0.2092th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

183 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic6
VUS88
Likely Benign4
Benign13
63
Pathogenic
6
Likely Pathogenic
88
VUS
4
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
63
0
63
Likely Pathogenic
0
0
6
0
6
VUS
0
67
21
0
88
Likely Benign
0
2
2
0
4
Benign
0
0
13
0
13
Total0691050174

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRIM58 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
TRIM58 functions as a tumor suppressor in colorectal cancer by promoting RECQL4 ubiquitination to inhibit the AKT signaling pathway
Sun N et al.·World J Surg Oncol
2023
Predictive and Prognostic Value of TRIM58 Protein Expression in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy
Zheng YZ et al.·Breast Cancer (Dove Med Press)
2022Cohort
[Correlation between the Promoter Methylation Status of TRIM58 and Its mRNA Expression in Acute Myeloid Leukemia].
DU CK et al.·Zhongguo Shi Yan Xue Ye Xue Za Zhi
2022
AUF1 Promotes Proliferation and Invasion of Thyroid Cancer via Downregulation of ZBTB2 and Subsequent TRIM58
Du X et al.·Front Oncol
2021
Silencing of the TRIM58 Gene by Aberrant Promoter Methylation is Associated with a Poor Patient Outcome and Promotes Cell Proliferation and Migration in Clear Cell Renal Cell Carcinoma
Gan Y et al.·Front Mol Biosci
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients