UBE2B

Chr 5

ubiquitin conjugating enzyme E2 B

Also known as: E2-17kDa, HHR6B, HR6B, RAD6B, UBC2

NCBI Gene: 7320ENSG00000119048UniProt: P63146

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. This enzyme is required for post-replicative DNA damage repair. Its protein sequence is 100% identical to the mouse, rat, and rabbit homologs, which indicates that this enzyme is highly conserved in eukaryotic evolution. [provided by RefSeq, Jul 2008]

25
ClinVar variants
16
Pathogenic / LP
0.20
pLI score
0
Active trials
Clinical Summary— UBE2B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 7 VUS of 25 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.70LOEUF
pLI 0.197
Z-score 2.24
OE 0.27 (0.12–0.70)
Tolerant

Typical tolerance to LoF variation

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.
2.18Z-score
OE missense 0.33 (0.24–0.45)
27 obs / 82.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.27 (0.12–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.33 (0.24–0.45)
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.1.25
0≤1.21.6
LoF obs/exp: 3 / 11.0Missense obs/exp: 27 / 82.8Syn Z: -1.04

ClinVar Variant Classifications

25 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS7
Likely Benign2
15
Pathogenic
1
Likely Pathogenic
7
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
3
4
0
7
Likely Benign
0
0
2
0
2
Benign
0
0
0
0
0
Total0322025

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

View in ClinVar →

Protein Context — Lollipop Plot

UBE2B · 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
A functional variant in the UBE2B gene promoter is associated with idiopathic azoospermia.
Mou L et al.·Reprod Biol Endocrinol
2015Functional
Surmounting cancer drug resistance: New insights from the perspective of N(6)-methyladenosine RNA modification.
Li B et al.·Drug Resist Updat
2020Review
Targeting UBE2B-mediated U2AF1 degradation to alleviate endothelial dysfunction in renal ischemia-reperfusion injury: therapeutic potential of semaglutide.
Wang Q et al.·Mol Biol Rep
2025
Histone H2B monoubiquitination regulates heart development via epigenetic control of cilia motility.
Robson A et al.·Proc Natl Acad Sci U S A
2019
High Expression of UBE2B as a Poor Prognosis Factor in Patients With Rectal Cancer Following Chemoradiotherapy.
Huang WL et al.·Anticancer Res
2020Cohort
Internal driving factors leading to extrahepatic manifestation of the hepatitis C virus infection.
Wu ZY et al.·Int J Mol Med
2017
Increased Expression of UBE2T Predicting Poor Survival of Epithelial Ovarian Cancer: Based on Comprehensive Analysis of UBE2s, Clinical Samples, and the GEO Database.
Zou R et al.·DNA Cell Biol
2021
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