UBE2U

Chr 1

ubiquitin conjugating enzyme E2 U

NCBI Gene: 148581 ENSG00000177414 UniProt: Q5VVX9 OMIM: 621653

This ubiquitin-conjugating enzyme catalyzes the covalent attachment of ubiquitin to other proteins and is involved in DNA repair and protein degradation pathways. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation. The gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable ubiquitin conjugating enzyme activity. Predicted to be involved in DNA repair; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein polyubiquitination. Predicted to be part of HULC complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.32

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.32LOEUF

pLI 0.000

Z-score 0.67

OE 0.81 (0.52–1.32)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.31Z-score

OE missense 0.92 (0.78–1.08)

101 obs / 110.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.81 (0.52–1.32)

0≤0.351.4

Missense OE?0.92 (0.78–1.08)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 12 / 14.8Missense obs/exp: 101 / 110.3Syn Z: -0.11

Background carrier burden — how many people carry a rare variant somewhere in UBE2U?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 95

367 rare PASS variants

Rare truncating (LoF)

1 in 480

106 rare PASS variants

Rare synonymous (reference)

1 in 420

112 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UBE2U. 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 160	1 in 660
South Asian	~43k	1 in 120	1 in 760
Remaining (unassigned)	~30k	1 in 110	1 in 280
European (Finnish)	~27k	1 in 600	1 in 1,100
Admixed American	~22k	1 in 160	1 in 370
African / African American	~21k	1 in 150	1 in 390
East Asian	~20k	1 in 170	1 in 460
Ashkenazi Jewish	~13k	1 in 740	none seen
Middle Eastern	~2,884	1 in 82	≈ 1 in 710

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): 9 of 10 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 10.? see exons ↓