TRIM39

Chr 6

tripartite motif containing 39

Also known as: RNF23, TFP, TRIM39B

NCBI Gene: 56658ENSG00000204599UniProt: Q9HCM9

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 function of this protein has not been identified. This gene lies within the major histocompatibility complex class I region on chromosome 6. Alternate splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

24
ClinVar variants
6
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TRIM39
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 13 VUS of 24 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.27LOEUF
pLI 0.995
Z-score 4.45
OE 0.10 (0.05–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
3.79Z-score
OE missense 0.40 (0.34–0.46)
124 obs / 312.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.10 (0.05–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.40 (0.34–0.46)
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.0.79
0≤1.21.6
LoF obs/exp: 3 / 28.8Missense obs/exp: 124 / 312.7Syn Z: 1.79

ClinVar Variant Classifications

24 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS13
Likely Benign5
5
Pathogenic
1
Likely Pathogenic
13
VUS
5
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
13
0
0
13
Likely Benign
0
5
0
0
5
Benign
0
0
0
0
0
Total0186024

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

View in ClinVar →

Protein Context — Lollipop Plot

TRIM39 · 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
TRIM39 reinforces E2-ESR1 signaling through SUMOylation of ESR1 to hinder the progression of aortic dissection.
Zhang D et al.·Atherosclerosis
2025
Nasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci.
Ning L et al.·Commun Biol
2020
TRIM39 is a poor prognostic factor for patients with estrogen receptor-positive breast cancer and promotes cell cycle progression.
Ogura T et al.·Pathol Int
2022Cohort
cGMP-dependent protein kinase I interacts with TRIM39R, a novel Rpp21 domain-containing TRIM protein.
Roberts JD Jr et al.·Am J Physiol Lung Cell Mol Physiol
2007
Sofosbuvir induces gene expression for promoting cell proliferation and migration of hepatocellular carcinoma cells.
Tsai WL et al.·Aging (Albany NY)
2022
Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus.
Kunz M et al.·Exp Dermatol
2015
Construction of a prognostic model for colon cancer by combining endoplasmic reticulum stress responsive genes.
Yuan Z et al.·J Proteomics
2024Functional
Autoantibody biomarkers for the detection of serous ovarian cancer.
Katchman BA et al.·Gynecol Oncol
2017
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