UCHL1

Chr 4ADAR

ubiquitin C-terminal hydrolase L1

Also known as: HEL-117, HEL-S-53, NDGOA, PARK5, PGP 9.5, PGP9.5, PGP95, SPG79

NCBI Gene: 7345ENSG00000154277UniProt: P09936OMIM: 191342

The protein encoded by this gene belongs to the peptidase C12 family. This enzyme is a thiol protease that hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. This gene is specifically expressed in the neurons and in cells of the diffuse neuroendocrine system. Mutations in this gene may be associated with Parkinson disease.[provided by RefSeq, Sep 2009]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{?Parkinson disease 5, susceptibility to}MIM #613643
AD
Spastic paraplegia 79A, autosomal dominantMIM #620221
AD
Spastic paraplegia 79B, autosomal recessiveMIM #615491
AR

Clinical highlights

Gene-disease validity (ClinGen)
hereditary spastic paraplegia · ARModerateconsider for supplementary testing2 gene-disease associations curated in total
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.
3
Active trials
136
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.21
LOEUF· LoF intol.
—
Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.21LOEUF
pLI 0.991
Z-score 3.48
OE 0.00 (0.00–0.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
0.70Z-score
OE missense 0.82 (0.70–0.97)
102 obs / 123.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.21)
0≤0.351.4
Missense OE?0.82 (0.70–0.97)
0≤0.61.4
Synonymous OE?1.42
0≤1.21.6
LoF obs/exp: 0 / 14.1Missense obs/exp: 102 / 123.9Syn Z: -2.27

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

UCHL1 · protein map & ClinVar variants

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

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