TRIM67

Chr 1

tripartite motif containing 67

Also known as: TNL

NCBI Gene: 440730 ENSG00000119283 UniProt: Q6ZTA4 OMIM: 610584

The protein is predicted to bind zinc ions and regulate protein localization, with involvement in Ras signaling regulation, neuron projection development, and ubiquitin-mediated protein degradation in the cytoplasm and cytoskeleton. TRIM67 is highly constrained against loss-of-function variants (pLI=0.97, LOEUF=0.33), suggesting mutations may cause severe developmental disorders, though specific disease associations have not yet been established. The inheritance pattern for TRIM67-related conditions has not been determined.

OMIM ResearchSummary from RefSeq

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.33

Clinical Summary— TRIM67

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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.

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ClinVar Variants

108 VUS of 113 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

1.74Z-score

OE missense 0.76 (0.70–0.84)

325 obs / 426.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.14 (0.07–0.33)

0≤0.351.4

Missense OE?0.76 (0.70–0.84)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 4 / 28.1Missense obs/exp: 325 / 426.1Syn Z: -0.24

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

VUS108

Likely Benign1

108

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	107	108
Likely Benign	0	1	1
Benign	0	0	0
Total	1	108	109

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap TRIM67 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →