UBL3

Chr 13

ubiquitin like 3

Also known as: HCG-1, PNSC1

NCBI Gene: 5412 ENSG00000122042 UniProt: O95164

UBL3 encodes a ubiquitin-like protein that is found in extracellular exosomes. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.544), but specific disease associations and inheritance patterns for UBL3 mutations have not been established. Clinical phenotypes resulting from UBL3 variants require further characterization.

ResearchSummary from RefSeq

Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating 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.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.54

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.54LOEUF

pLI 0.735

Z-score 2.42

OE 0.11 (0.04–0.54)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.29Z-score

OE missense 0.55 (0.42–0.72)

35 obs / 64.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.54)

0≤0.351.4

Missense OE?0.55 (0.42–0.72)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 1 / 8.7Missense obs/exp: 35 / 64.1Syn Z: 0.77

Background carrier burden — how many people carry a rare variant somewhere in UBL3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,100

113 rare PASS variants

Rare truncating (LoF)

1 in 27,000

13 rare PASS variants

Rare synonymous (reference)

1 in 370

52 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UBL3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 7 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 1,500	1 in 20,000
South Asian	~43k	1 in 660	none seen
Remaining (unassigned)	~30k	1 in 1,600	≈ 1 in 15,000
Admixed American	~22k	1 in 510	none seen
African / African American	~21k	1 in 1,400	≈ 1 in 8,300
East Asian	~20k	1 in 550	≈ 1 in 20,000
Middle Eastern	~2,884	≈ 1 in 960	none seen

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓