TRIM26

Chr 6

tripartite motif containing 26

Also known as: RNF95, ZNF173

NCBI Gene: 7726ENSG00000234127UniProt: Q12899

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. Although the function of the protein is unknown, the RING domain suggests that the protein may have DNA-binding activity. The gene localizes to the major histocompatibility complex (MHC) class I region on chromosome 6. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2011]

69
ClinVar variants
6
Pathogenic / LP
0.18
pLI score
0
Active trials
Clinical Summary— TRIM26
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 49 VUS of 69 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.46LOEUF
pLI 0.178
Z-score 3.71
OE 0.25 (0.14–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.09Z-score
OE missense 0.52 (0.46–0.59)
171 obs / 328.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.14–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.46–0.59)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90
0≤1.21.6
LoF obs/exp: 7 / 28.3Missense obs/exp: 171 / 328.6Syn Z: 0.95

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS49
Likely Benign14
5
Pathogenic
1
Likely Pathogenic
49
VUS
14
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
47
2
0
49
Likely Benign
0
14
0
0
14
Benign
0
0
0
0
0
Total0618069

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

View in ClinVar →

Protein Context — Lollipop Plot

TRIM26 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RBM4 dictates ESCC cell fate switch from cellular senescence to glutamine-addiction survival through inhibiting LKB1-AMPK-axis.
Chen L et al.·Signal Transduct Target Ther
2023
USP39 stabilizes β-catenin by deubiquitination and suppressing E3 ligase TRIM26 pre-mRNA maturation to promote HCC progression.
Wang W et al.·Cell Death Dis
2023
TRIM26 deficiency potentially suppresses colorectal cancer liver metastasis through NF-κB-mediated M1-like tumor-associated macrophage polarization.
Zhong W et al.·Br J Cancer
2025
Inhibition of the PI3K/AKT signaling pathway blocks the oncogenic activity of TRIM26 in prostate cancer cells.
Zhong YY et al.·Asian J Androl
2026
Association study between TRIM26 polymorphisms and risk of aspirin-exacerbated respiratory disease.
Lee JS et al.·Int J Mol Med
2012
P2X7R deficiency alleviates cardiac senescence by enhancing mitophagy via the HuR/TRIM26/NR4A1 axis.
Zhou Y et al.·Clin Transl Med
2026
Construction and multiple validations of a robust ferroptosis-related prognostic model in bladder cancer: A comprehensive study.
Dai X et al.·Medicine (Baltimore)
2024Functional
Comprehensive analysis reveals common DNA methylation patterns of tobacco-associated cancers: A pan-cancer analysis.
Liu X et al.·Gene
2021
TAggiXL: A Fluorescence-Traceable Cross-Linking Strategy for Unbiased Profiling of Protein Aggregation and Interactome Dynamics.
Chen Y et al.·Anal Chem
2024
The impact of the genome-wide supported variant in the cyclin M2 gene on gray matter morphology in schizophrenia.
Ohi K et al.·Behav Brain Funct
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools