UBE2G1

Chr 17

ubiquitin conjugating enzyme E2 G1

Also known as: E217K, UBC7, UBE2G

NCBI Gene: 7326 ENSG00000132388 UniProt: P62253

This protein is a ubiquitin-conjugating enzyme (E2) that catalyzes the covalent attachment of ubiquitin to target proteins, including muscle-specific proteins and CYP3A4. The gene is highly constrained against loss-of-function variants (pLI = 0.84, LOEUF = 0.45), suggesting mutations would likely cause severe disease, but no specific genetic disorders have been definitively associated with UBE2G1 mutations to date.

ResearchSummary from RefSeq, UniProt

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 and catalyzes the covalent attachment of ubiquitin to other proteins. The protein may be involved in degradation of muscle-specific proteins. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.45

Clinical Summary— UBE2G1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.84) — some intolerance to loss-of-function variants.

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ClinVar Variants

10 total variants — no pathogenic classifications of 10 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.844

Z-score 2.71

OE 0.10 (0.03–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.38Z-score

OE missense 0.28 (0.21–0.40)

25 obs / 87.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.10 (0.03–0.45)

0≤0.351.4

Missense OE?0.28 (0.21–0.40)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 1 / 10.5Missense obs/exp: 25 / 87.7Syn Z: -0.24

This gene — mechanism propensity

0.5279th %ile

GOF

0.6833th %ile

LOF

0.48top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

10 submitted variants in ClinVar

ClinVar

Classification Summary

Curated Variants Distribution

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

Classification	LoF	Missense + Inframe	Non-coding	Synonymous
Pathogenic	—	—	—	—
Likely Pathogenic	—	—	—	—
VUS	—	—	—	—
Likely Benign	—	—	—	—
Benign	—	—	—	—
Total	—

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

24 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap UBE2G1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →