UCHL1

Chr 4

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: P09936

The protein is a deubiquitinase that hydrolyzes peptide bonds at the C-terminal glycine of ubiquitin and regulates multiple cellular processes including synaptic function and protein degradation pathways. Mutations cause spastic paraplegia 79A (autosomal dominant) and spastic paraplegia 79B (autosomal recessive), with potential susceptibility to Parkinson disease. The gene is highly constrained against loss-of-function mutations (pLI 0.99, LOEUF 0.21), indicating that complete loss of protein function is likely not tolerated.

ResearchSummary from RefSeq, OMIM, UniProt
LOEUF 0.21
Clinical Summary— UCHL1
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Gene-Disease Validity (ClinGen)
hereditary spastic paraplegia · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
42 unique Pathogenic / Likely Pathogenic· 84 VUS of 256 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE0.00 (0.00–0.21)
0≤0.351.4
Missense OE0.82 (0.70–0.97)
0≤0.61.4
Synonymous OE1.42
0≤1.21.6
LoF obs/exp: 0 / 14.1Missense obs/exp: 102 / 123.9Syn Z: -2.27

ClinVar Variant Classifications

256 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic13
VUS84
Likely Benign92
Benign25
Conflicting3
29
Pathogenic
13
Likely Pathogenic
84
VUS
92
Likely Benign
25
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
2
17
0
29
Likely Pathogenic
11
2
0
0
13
VUS
5
55
24
0
84
Likely Benign
0
2
54
36
92
Benign
0
1
24
0
25
Conflicting
—3
Total266211936246

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

View in 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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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