UCHL3

Chr 13

ubiquitin C-terminal hydrolase L3

Also known as: UCH-L3

NCBI Gene: 7347 ENSG00000118939 UniProt: P15374

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.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the deubiquitinating enzyme family. Members of this family are proteases that catalyze the removal of ubiquitin from polypeptides and are divided into five classes, depending on the mechanism of catalysis. This protein may hydrolyze the ubiquitinyl-N-epsilon amide bond of ubiquitinated proteins to regenerate ubiquitin for another catalytic cycle. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in UCHL3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

324 rare PASS variants

Rare truncating (LoF)

1 in 1,400

70 rare PASS variants

Rare synonymous (reference)

1 in 1,000

126 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UCHL3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 330	1 in 1,400
South Asian	~43k	1 in 190	1 in 2,900
Remaining (unassigned)	~30k	1 in 260	1 in 3,500
European (Finnish)	~27k	1 in 500	≈ 1 in 8,800
Admixed American	~22k	1 in 260	1 in 2,200
African / African American	~21k	1 in 190	1 in 1,600
East Asian	~20k	1 in 180	1 in 370
Ashkenazi Jewish	~13k	1 in 810	none seen
Middle Eastern	~2,884	1 in 290	1 in 530

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓