TRIM63
Chr 1ARtripartite motif containing 63
Also known as: CMH31, IRF, MURF1, MURF2, RNF28, SMRZ
The protein is an E3 ubiquitin ligase that localizes to myofibrils and mediates the ubiquitination and degradation of muscle proteins including myosin heavy chain, creatine kinase, and cardiac troponin I, playing a crucial role in muscle protein turnover and atrophy. Mutations cause hypertrophic cardiomyopathy with autosomal dominant inheritance. The gene shows very low constraint against loss-of-function variants, suggesting tolerance to such mutations.
Disputed — evidence questions this relationship
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
171 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 2 | 1 | 6 | 0 | 9 |
Likely Pathogenic | 3 | 0 | 0 | 0 | 3 |
VUS | 5 | 87 | 5 | 0 | 97 |
Likely Benign | 0 | 4 | 12 | 18 | 34 |
Benign | 0 | 0 | 18 | 3 | 21 |
Conflicting | — | 7 | |||
| Total | 10 | 92 | 41 | 21 | 171 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TRIM63 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools