TRIM2

Chr 4AR

tripartite motif containing 2

Also known as: CMT2R, RNF86

NCBI Gene: 23321ENSG00000109654UniProt: Q9C040

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 filaments. It plays a neuroprotective role and functions as an E3-ubiquitin ligase in proteasome-mediated degradation of target proteins. Mutations in this gene can cause early-onset axonal neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, type 2RMIM #615490
AR
581
ClinVar variants
32
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TRIM2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 274 VUS of 581 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 0.996
Z-score 4.76
OE 0.12 (0.06–0.27)
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.
3.57Z-score
OE missense 0.53 (0.48–0.59)
248 obs / 464.6 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.0.12 (0.06–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.53 (0.48–0.59)
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.0.89
0≤1.21.6
LoF obs/exp: 4 / 34.0Missense obs/exp: 248 / 464.6Syn Z: 1.19

ClinVar Variant Classifications

581 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic5
VUS274
Likely Benign246
Benign24
Conflicting5
27
Pathogenic
5
Likely Pathogenic
274
VUS
246
Likely Benign
24
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
24
0
27
Likely Pathogenic
1
1
3
0
5
VUS
10
244
18
2
274
Likely Benign
0
7
73
166
246
Benign
0
0
19
5
24
Conflicting
—5
Total13253137173581

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

View in ClinVar →

Protein Context — Lollipop Plot

TRIM2 · 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

Charcot-Marie-Tooth disease, type 2R

MIM #615490

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TRIM2 inhibits apoptosis by ubiquitinating BNIP3 to protect the intestine against ischemia-reperfusion injury in mice.
Nie J et al.·Commun Biol
2025
In-vitro immunomodulatory efficacy of extracellular vesicles derived from TGF-β1/IFN-γ dual licensed human bone marrow mesenchymal stromal cells.
Wang J et al.·Stem Cell Res Ther
2025
Gene expression-phenotype associations in adults with eosinophilic esophagitis.
Dellon ES et al.·Dig Liver Dis
2018
GPER promotes tamoxifen-resistance in ER+ breast cancer cells by reduced Bim proteins through MAPK/Erk-TRIM2 signaling axis.
Yin H et al.·Int J Oncol
2017
Expanding the phenotypic spectrum of TRIM2-associated Charcot-Marie-Tooth disease.
Magri S et al.·J Peripher Nerv Syst
2020Case report
TRIM2 exacerbates the advancement of idiopathic pulmonary fibrosis by modulating β-catenin and endoplasmic reticulum stress.
Zhang Y et al.·Eur J Med Res
2025
ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.
Montecchiani C et al.·Brain
2016
Genomic analysis reveals molecular characterization of CD30(+) and CD30(-) extranodal natural killer/T-cell lymphomas (ENKTLs).
Zhang X et al.·Hum Pathol
2024
Exploring Neuronal Vulnerability to Head Trauma Using a Whole Exome Approach.
Ibrahim O et al.·J Neurotrauma
2020
Construction of circRNA-based ceRNA network to reveal the role of circRNAs in the progression and prognosis of metastatic clear cell renal cell carcinoma.
Wei X et al.·Aging (Albany NY)
2020
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