TRIM67

Chr 1

tripartite motif containing 67

Also known as: TNL

NCBI Gene: 440730ENSG00000119283UniProt: Q6ZTA4

Predicted to enable zinc ion binding activity. Predicted to be involved in regulation of protein localization. Predicted to act upstream of or within negative regulation of Ras protein signal transduction; positive regulation of neuron projection development; and positive regulation of ubiquitin-dependent protein catabolic process. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

162
ClinVar variants
38
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TRIM67
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
38 Pathogenic / Likely Pathogenic· 117 VUS of 162 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.33LOEUF
pLI 0.965
Z-score 4.21
OE 0.14 (0.07–0.33)
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.
1.74Z-score
OE missense 0.76 (0.70–0.84)
325 obs / 426.1 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.0.14 (0.07–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.70–0.84)
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.1.02
0≤1.21.6
LoF obs/exp: 4 / 28.1Missense obs/exp: 325 / 426.1Syn Z: -0.24

ClinVar Variant Classifications

162 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic2
VUS117
Likely Benign2
36
Pathogenic
2
Likely Pathogenic
117
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
2
0
2
VUS
1
106
10
0
117
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Total1107490157

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

View in ClinVar →

Protein Context — Lollipop Plot

TRIM67 · 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
Autoimmune Movement Disorders.
Balint B·Continuum (Minneap Minn)
2024Review
TRIM67 drives tumorigenesis in oligodendrogliomas through Rho GTPase-dependent membrane blebbing.
Demirdizen E et al.·Neuro Oncol
2023
Detection of High-Risk Paraneoplastic Antibodies against TRIM9 and TRIM67 Proteins.
Bartley CM et al.·Ann Neurol
2023
Placental DNA methylation changes in gestational diabetes mellitus.
Chen F et al.·Epigenetics
2022
PCK2 promotes invasion and epithelial-to-mesenchymal transition in triple-negative breast cancer by promoting TGF-β/SMAD3 signaling through inhibiting TRIM67-mediated SMAD3 ubiquitination.
Chang TM et al.·Cancer Biol Ther
2025
Exosome-Derived Circ_0094343 Promotes Chemosensitivity of Colorectal Cancer Cells by Regulating Glycolysis via the miR-766-5p/TRIM67 Axis.
Li C et al.·Contrast Media Mol Imaging
2022
Phenotype expansion of variants affecting p38 MAPK signaling in hypospadias patients.
Lin D et al.·Orphanet J Rare Dis
2022Cohort
Explainable cancer factors discovery: Shapley additive explanation for machine learning models demonstrates the best practices in the case of pancreatic cancer.
Su L et al.·Pancreatology
2024Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Remimazolam Inhibits Neuronal Apoptosis, Inflammation, and Ferroptosis in Cerebral Infarction via Promoting TRIM67-Mediated Degradation of ACSL4.
Xiao G et al.·J Biochem Mol Toxicol
2026
TRIM67 Suppresses Glioblastoma Glycolysis and Increases Temozolomide Sensitivity by Promoting ARSD Ubiquitinated Degradation to Inactivate the β-Catenin Pathway.
Li X et al.·FASEB J
2025
Coro1A and TRIM67 collaborate in netrin-dependent neuronal morphogenesis.
Ho CT et al.·J Cell Biol
2025
Effect of TRIM67 knockout on inflammation and macrophage survival in Salmonella Typhimurium-infected mice.
Chen S et al.·Arch Microbiol
2025
The Impact of TRIM67 Knockout on Early Intestinal Antimicrobial Capacity in Mice Infected with Salmonella enterica serovar Typhimurium ATCC 14028.
Zhang X et al.·Microorganisms
2025🔓 Open Access
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