UBE2I

Chr 16

ubiquitin conjugating enzyme E2 I

Also known as: C358B7.1, P18, UBC9

NCBI Gene: 7329ENSG00000103275UniProt: P63279

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]

78
ClinVar variants
48
Pathogenic / LP
0.96
pLI score· haploinsufficient
0
Active trials
Clinical Summary— UBE2I
⚡
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
48 Pathogenic / Likely Pathogenic· 13 VUS of 78 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.10 (0.06–0.17)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.48
0≤1.21.6
LoF obs/exp: 0 / 10.4Missense obs/exp: 9 / 93.0Syn Z: -2.41

ClinVar Variant Classifications

78 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic1
VUS13
Benign4
47
Pathogenic
1
Likely Pathogenic
13
VUS
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————47
Likely Pathogenic
————1
VUS
————13
Likely Benign
————0
Benign
————4
Total—65

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

UBE2I · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
UBE2I depletion regulated tumor-associated macrophage polarization into M1 type through reprogramming glycolysis and increases immunotherapy efficacy of anti-PD-L1 in ovarian cancer.
Zhao L et al.·Mol Immunol
2025
Upregulation of miRNA-10a-5p promotes tumor progression in cervical cancer by suppressing UBE2I signaling.
Gu Y et al.·J Obstet Gynaecol
2023Meta-analysis
Targeting protein hyper-SUMOylation halts cholangiocarcinoma progression by impairing cancer cell viability and tumor-stroma cross talk.
Olaizola P et al.·Hepatology
2025
UBC9 overexpression promotes proliferation and metastasis in gastric cancer via ATF2.
Wang Q et al.·World J Surg Oncol
2025
Identification of a novel microRNA-mRNA regulatory biomodule in human prostate cancer.
Zhang Y et al.·Cell Death Dis
2018
A framework for exhaustively mapping functional missense variants.
Weile J et al.·Mol Syst Biol
2017Functional
Proteasome Dysregulation in Parkinson's Disease: Insights from Blood-Based Analyses.
Di Costanzo A et al.·Mol Neurobiol
2025
Identification of post-translational modification-related biomarkers in ischemic stroke using bioinformatics and machine learning.
Bian X et al.·Sci Rep
2025
Novel PDGFRB Gene Fusions in Two Cases of Infantile Myofibromatosis.
Boccia F et al.·Genes Chromosomes Cancer
2025Case report
A comprehensive protein interaction map and druggability investigation prioritized dengue virus NS1 protein as promising therapeutic candidate.
Farooq QUA et al.·PLoS One
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools