TRIM58

Chr 1

tripartite motif containing 58

Also known as: BIA2

NCBI Gene: 25893 ENSG00000162722 UniProt: Q8NG06 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.56

Clinical Summary— TRIM58

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

67 VUS of 78 total submissions

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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 OE?1.02 (0.68–1.56)

0≤0.351.4

Missense OE?0.92 (0.83–1.03)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 15 / 14.7Missense obs/exp: 219 / 237.1Syn Z: -0.76

This gene — mechanism propensity

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

78 submitted variants in ClinVar

ClinVar

Classification Summary

VUS67

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	67	67
Likely Benign	2	2
Benign	0	0
Total	69	69

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

View in ClinVar →

69 pathogenic / likely-pathogenic (of 105) ClinVar copy-number / structural variants overlap TRIM58 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →