UBE2D2

Chr 5

ubiquitin conjugating enzyme E2 D2

Also known as: E2(17)KB2, PUBC1, UBC4, UBC4/5, UBCH4, UBCH5B

NCBI Gene: 7322ENSG00000131508UniProt: P62837

Regulated degradation of misfolded, damaged or short-lived proteins in eukaryotes occurs via the ubiquitin (Ub)-proteasome system (UPS). An integral part of the UPS system is the ubiquitination of target proteins and covalent linkage of Ub-containing proteins to form polymeric chains, marking them as targets for 26S proteasome-mediated degradation. Ubiquitination of proteins is mediated by a cascade of enzymes which includes E1 (ubiquitin activating), E2 (ubiquitin conjugating), and E3 (ubiquitin ligases) enzymes. This gene encodes a member of the E2 enzyme family. Substrates of this enzyme include the tumor suppressor protein p53 and peroxisomal biogenesis factor 5 (PEX5). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

24
ClinVar variants
13
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— UBE2D2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 10 VUS of 24 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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 3.00
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.
2.96Z-score
OE missense 0.07 (0.04–0.15)
6 obs / 80.9 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.0.00 (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.0.07 (0.04–0.15)
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.0.75
0≤1.21.6
LoF obs/exp: 0 / 10.5Missense obs/exp: 6 / 80.9Syn Z: 0.97

ClinVar Variant Classifications

24 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic1
VUS10
Likely Benign1
12
Pathogenic
1
Likely Pathogenic
10
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
1
0
1
VUS
0
4
6
0
10
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total0420024

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

View in ClinVar →

Protein Context — Lollipop Plot

UBE2D2 · 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
UBE2D2 promotes gastric cancer progression by inhibiting ferroptosis through autophagy-dependent stabilization of CST1.
Yang Y et al.·Int J Biol Macromol
2025
miR-30b-5p releases HMGB1 via UBE2D2/KAT2B/HMGB1 pathway to promote pro-inflammatory polarization and recruitment of macrophages.
Qi X et al.·Atherosclerosis
2021
The cuproptosis-related gene UBE2D2 functions as an immunotherapeutic and prognostic biomarker in pan-cancer.
Fei Y et al.·Clin Transl Oncol
2024
Integrated transcriptomic analysis identifies lysosomal autophagy-related genes in sarcopenia.
Zhou Y et al.·Sci Rep
2025
Multi-omics identification of circulating protein biomarkers for intervertebral disc degeneration using Mendelian randomization and scRNA-seq.
Bai F et al.·Clin Rheumatol
2025
NleG Type 3 effectors from enterohaemorrhagic Escherichia coli are U-Box E3 ubiquitin ligases.
Wu B et al.·PLoS Pathog
2010
Identification of prognosis biomarkers of prostatic cancer in a cohort of 498 patients from TCGA.
Chen Z et al.·Curr Probl Cancer
2019Cohort
Reliable reference genes for the quantification of mRNA in human T-cells and PBMCs stimulated with live influenza virus.
Roy JG et al.·BMC Immunol
2020
Downregulation of the ubiquitin-proteasome system in normal colonic macrophages and reinduction in inflammatory bowel disease.
Hetzenecker AM et al.·Digestion
2012
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