UBE2G2

Chr 21

ubiquitin conjugating enzyme E2 G2

Also known as: UBC7

NCBI Gene: 7327ENSG00000184787UniProt: P60604

UBE2G2 encodes an E2 ubiquitin-conjugating enzyme that accepts ubiquitin from E1 enzymes and catalyzes its covalent attachment to target proteins, particularly facilitating endoplasmic reticulum-associated degradation (ERAD) pathways. Mutations cause autosomal recessive intellectual disability with early-onset seizures and developmental delays. The gene shows relatively low constraint to loss-of-function variation, consistent with recessive inheritance patterns.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
93
P/LP submissions
0%
P/LP missense
0.86
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— UBE2G2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
88 unique Pathogenic / Likely Pathogenic· 33 VUS of 125 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.099
Z-score 1.85
OE 0.33 (0.15–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.80Z-score
OE missense 0.49 (0.39–0.62)
48 obs / 98.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.15–0.86)
0≤0.351.4
Missense OE0.49 (0.39–0.62)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 3 / 9.0Missense obs/exp: 48 / 98.2Syn Z: -0.04
DN
0.6938th %ile
GOF
0.73top 25%
LOF
0.2582th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

125 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic84
Likely Pathogenic4
VUS33
Conflicting1
84
Pathogenic
4
Likely Pathogenic
33
VUS
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
84
0
84
Likely Pathogenic
0
0
4
0
4
VUS
0
16
17
0
33
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Conflicting
—1
Total0161050122

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

View in ClinVar →

Protein Context — Lollipop Plot

UBE2G2 · protein map & ClinVar variants

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

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 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
RNA m6A reader YTHDF3/ UBE2G2 m6A methylation/ ACSL4 ubiquitination axis facilitated cell ferroptosis to mediate benzene hematotoxicity and the protective effect of melatonin.
Wang J et al.·Ecotoxicol Environ Saf
2025
AUP1 and UBE2G2 complex targets STING signaling and regulates virus-induced innate immunity.
Wang X-T et al.·mBio
2025Open Access
A nanobody that binds to the backside of the ubiquitin conjugating enzyme Ube2G2 differentially affects interactions with its partner E3 Ligases.
Suresh P et al.·Commun Biol
2025Open Access
UBE2G2 inhibits vasculogenic mimicry and metastasis of uveal melanoma by promoting ubiquitination of LGALS3BP.
Zhao A et al.·Acta Pharm Sin B
2024Open Access
Proinsulin degradation and presentation of a proinsulin B-chain autoantigen involves ER-associated protein degradation (ERAD)-enzyme UBE2G2.
Cremer T et al.·PLoS One
2024Open Access
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