USP46

Chr 4

ubiquitin specific peptidase 46

NCBI Gene: 64854ENSG00000109189UniProt: P62068OMIM: 612849

Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP46 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Jun 2009]

OMIMResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
20
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.42
LOEUF
—
Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.42LOEUF
pLI 0.791
Z-score 3.32
OE 0.16 (0.07–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.87Z-score
OE missense 0.43 (0.36–0.51)
85 obs / 198.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.16 (0.07–0.42)
0≤0.351.4
Missense OE?0.43 (0.36–0.51)
0≤0.61.4
Synonymous OE?0.74
0≤1.21.6
LoF obs/exp: 3 / 18.3Missense obs/exp: 85 / 198.7Syn Z: 1.75

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

USP46 · protein map & ClinVar variants

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

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients