UBE2E2

Chr 3

ubiquitin conjugating enzyme E2 E2

Also known as: UBCH8

NCBI Gene: 7325ENSG00000182247UniProt: Q96LR5OMIM: 602163

UBE2E2 encodes a ubiquitin-conjugating enzyme that transfers ubiquitin and ISG15 to target proteins, catalyzing polyubiquitination through multiple lysine linkages and playing a role in DNA damage response and cell cycle regulation. The gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.29), but no established Mendelian disease associations have been reported to date. If pathogenic variants are identified, inheritance pattern would likely be autosomal recessive given the high constraint metrics.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.29
Clinical Summary— UBE2E2
⚡
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.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 15 VUS of 39 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.964
Z-score 2.98
OE 0.00 (0.00–0.29)
Highly constrained

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

Missense Constraint
2.29Z-score
OE missense 0.39 (0.31–0.51)
44 obs / 112.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.29)
0≤0.351.4
Missense OE0.39 (0.31–0.51)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 0 / 10.3Missense obs/exp: 44 / 112.1Syn Z: -0.84
DN
0.3793th %ile
GOF
0.4283th %ile
LOF
0.71top 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

39 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
VUS15
Likely Benign1
21
Pathogenic
15
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
0
0
0
VUS
0
13
2
0
15
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total01324037

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

View in ClinVar →

Protein Context — Lollipop Plot

UBE2E2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
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 3 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