TRIM64B

Chr 11

tripartite motif containing 64B

NCBI Gene: 642446ENSG00000189253UniProt: A6NI03

TRIM64B encodes a protein predicted to function as a ubiquitin protein ligase involved in innate immune response and gene regulation. The gene shows low constraint against loss-of-function variants (pLI 0.00001, LOEUF 1.30), suggesting that haploinsufficiency may be well-tolerated. No definitive disease associations have been established for TRIM64B mutations.

ResearchSummary from RefSeq
MultiplemechanismLOEUF 1.30
Clinical Summary— TRIM64B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 101 VUS of 125 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
1.30LOEUF
pLI 0.000
Z-score 0.81
OE 0.75 (0.45–1.30)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.34Z-score
OE missense 0.72 (0.63–0.83)
136 obs / 187.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.75 (0.45–1.30)
0≤0.351.4
Missense OE0.72 (0.63–0.83)
0≤0.61.4
Synonymous OE0.66
0≤1.21.6
LoF obs/exp: 9 / 12.0Missense obs/exp: 136 / 187.7Syn Z: 2.25
DN
0.86top 5%
GOF
0.83top 10%
LOF
0.10100th %ile

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.

DNprediction above median
GOFprediction 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

125 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS101
Likely Benign5
Benign1
16
Pathogenic
1
Likely Pathogenic
101
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
0
94
7
0
101
Likely Benign
0
1
4
0
5
Benign
0
0
1
0
1
Total095290124

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

View in ClinVar →

Protein Context — Lollipop Plot

TRIM64B · 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
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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