UBE2I

Chr 16

ubiquitin conjugating enzyme E2 I

Also known as: C358B7.1, P18, UBC9

NCBI Gene: 7329 ENSG00000103275 UniProt: P63279

UBE2I encodes an E2 conjugating enzyme that catalyzes the covalent attachment of small ubiquitin-like modifier (SUMO) proteins to target proteins, which is essential for nuclear architecture and chromosome segregation. This gene is highly constrained against loss-of-function variants (pLI=0.96), but no Mendelian disease associations have been established in OMIM or other major disease databases. Clinical variants in UBE2I would likely require careful evaluation given the protein's essential cellular functions.

ResearchSummary from RefSeq, UniProt

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. Four alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.29

Clinical Summary— UBE2I

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

1 VUS of 17 total submissions

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

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.29LOEUF

pLI 0.965

Z-score 2.99

OE 0.00 (0.00–0.29)

Highly constrained

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

Missense Constraint?

3.10Z-score

OE missense 0.10 (0.06–0.17)

9 obs / 93.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.29)

0≤0.351.4

Missense OE?0.10 (0.06–0.17)

0≤0.61.4

Synonymous OE?1.48

0≤1.21.6

LoF obs/exp: 0 / 10.4Missense obs/exp: 9 / 93.0Syn Z: -2.41

This gene — mechanism propensity

0.4090th %ile

GOF

0.5268th %ile

LOF

0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

17 submitted variants in ClinVar

ClinVar

Classification Summary

VUS1

Benign3

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	0	0	1
Likely Benign	0	0	0	0
Benign	0	2	1	3
Total	1	2	1	4

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

View in ClinVar →

48 pathogenic / likely-pathogenic (of 61) ClinVar copy-number / structural variants overlap UBE2I — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →