TRIM56

Chr 7

tripartite motif containing 56

Also known as: RNF109

NCBI Gene: 81844ENSG00000169871UniProt: Q9BRZ2

Enables ubiquitin protein ligase activity. Involved in defense response to virus; positive regulation of signal transduction; and protein monoubiquitination. Predicted to be located in cytoplasm. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

162
ClinVar variants
20
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TRIM56
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 131 VUS of 162 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.90LOEUF
pLI 0.000
Z-score 1.89
OE 0.51 (0.31–0.90)
Tolerant

Typical tolerance to LoF variation

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.
1.25Z-score
OE missense 0.84 (0.77–0.91)
397 obs / 473.8 exp
Tolerant

Mild missense constraint

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.0.51 (0.31–0.90)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.77–0.91)
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.1.08
0≤1.21.6
LoF obs/exp: 9 / 17.5Missense obs/exp: 397 / 473.8Syn Z: -0.89

ClinVar Variant Classifications

162 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic2
VUS131
Likely Benign9
Benign2
18
Pathogenic
2
Likely Pathogenic
131
VUS
9
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
2
0
2
VUS
0
124
7
0
131
Likely Benign
0
8
0
1
9
Benign
0
1
0
1
2
Total0133272162

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

View in ClinVar →

Protein Context — Lollipop Plot

TRIM56 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Disassembly of the TRIM56-ATR complex promotes cytoDNA/cGAS/STING axis-dependent intervertebral disc inflammatory degeneration.
Zhang W et al.·J Clin Invest
2024
TRIM56-mediated production of type I interferon inhibits intracellular replication of Rickettsia rickettsii.
Cheng R et al.·Microbiol Spectr
2024
TRIM56 suppresses the malignant development of hepatocellular carcinoma via targeting RBM24 and inactivating the Wnt signaling.
Yang Y et al.·Eur Rev Med Pharmacol Sci
2021
Overlapping and distinct molecular determinants dictating the antiviral activities of TRIM56 against flaviviruses and coronavirus.
Liu B et al.·J Virol
2014
PGRMC1 promotes NSCLC stemness phenotypes by disrupting TRIM56-mediated ubiquitination of AHR.
Guan A et al.·Biochim Biophys Acta Mol Basis Dis
2024
New Avenues to Explore in SARS-CoV-2 Infection: Both TRIM25 and TRIM56 Positively Correlate with VEGF, GAS6, and sAXL in COVID-19 Patients.
Baskol G et al.·Viral Immunol
2022Cohort
ZC3H15 regulates the ubiquitination of PTEN via recruitment of TRIM56 and promotes malignant progression of non-small cell lung cancer.
Wu P et al.·Cell Death Dis
2026
Circulating CD8 lymphocytes predict response to atezolizumab-bevacizumab in hepatocellular carcinoma.
Gramantieri L et al.·Eur J Immunol
2024
Bufei formula attenuates airway mucus hypersecretion in COPD through inhibition of TRIM56-mediated ITGB4 ubiquitination.
Xin N et al.·J Ethnopharmacol
2026
Tumor suppressor genes FHIT and WWOX are deleted in primary effusion lymphoma (PEL) cell lines.
Roy D et al.·Blood
2011
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