TRIM74

Chr 7

tripartite motif containing 74

Also known as: TRIM50C

The protein is predicted to function as a ubiquitin protein ligase involved in innate immune responses and is located in the cytosol. TRIM74 is not well-established as a cause of human disease, with limited clinical data available. The gene shows tolerance to loss-of-function variants (pLI 0.009, LOEUF 1.27), suggesting that complete loss of function may not cause severe developmental phenotypes.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.27
Clinical SummaryTRIM74
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 2 VUS of 29 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.27LOEUF
pLI 0.009
Z-score 1.09
OE 0.56 (0.271.27)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.65Z-score
OE missense 0.83 (0.700.98)
91 obs / 110.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.271.27)
00.351.4
Missense OE0.83 (0.700.98)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 4 / 7.2Missense obs/exp: 91 / 110.3Syn Z: 0.16
DN
0.84top 10%
GOF
0.84top 5%
LOF
0.1399th %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

29 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic3
VUS2
24
Pathogenic
3
Likely Pathogenic
2
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
Likely Pathogenic
3
VUS
2
Likely Benign
0
Benign
0
Total29

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRIM74 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found