UCHL3

Chr 13

ubiquitin C-terminal hydrolase L3

Also known as: UCH-L3

The encoded protein is a deubiquitinating enzyme that removes ubiquitin from target proteins and processes ubiquitin precursors to maintain cellular ubiquitin levels. Biallelic mutations cause autosomal recessive spastic paraplegia with intellectual disability, typically presenting in early childhood with progressive lower limb spasticity and developmental delays. This gene shows very low constraint against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.31
Clinical SummaryUCHL3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
69 unique Pathogenic / Likely Pathogenic· 29 VUS of 115 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.31LOEUF
pLI 0.000
Z-score 0.65
OE 0.82 (0.541.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.04Z-score
OE missense 0.73 (0.610.87)
87 obs / 118.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.82 (0.541.31)
00.351.4
Missense OE0.73 (0.610.87)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 13 / 15.8Missense obs/exp: 87 / 118.9Syn Z: 0.07

ClinVar Variant Classifications

115 submitted variants in ClinVar

Classification Summary

Pathogenic69
VUS29
Likely Benign1
69
Pathogenic
29
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
69
0
69
Likely Pathogenic
0
0
0
0
0
VUS
0
22
7
0
29
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total02376099

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

View in ClinVar →

Protein Context — Lollipop Plot

UCHL3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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