UBE2L3

Chr 22

ubiquitin conjugating enzyme E2 L3

Also known as: E2-F1, L-UBC, UBCH7, UbcM4

NCBI Gene: 7332ENSG00000185651UniProt: P68036

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 (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is demonstrated to participate in the ubiquitination of p53, c-Fos, and the NF-kB precursor p105 in vitro. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

136
ClinVar variants
97
Pathogenic / LP
0.84
pLI score
0
Active trials
Clinical Summary— UBE2L3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.84) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
97 Pathogenic / Likely Pathogenic· 22 VUS of 136 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.50LOEUF
pLI 0.838
Z-score 2.27
OE 0.00 (0.00–0.50)
Moderately constrained

More LoF-intolerant than ~75% 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.
2.88Z-score
OE missense 0.11 (0.07–0.19)
9 obs / 82.6 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 (0.00–0.50)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.11 (0.07–0.19)
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.0.69
0≤1.21.6
LoF obs/exp: 0 / 6.0Missense obs/exp: 9 / 82.6Syn Z: 1.35

ClinVar Variant Classifications

136 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic93
Likely Pathogenic4
VUS22
Likely Benign1
Benign3
93
Pathogenic
4
Likely Pathogenic
22
VUS
1
Likely Benign
3
Benign

Curated Variants Distribution

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

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————93
Likely Pathogenic
————4
VUS
————22
Likely Benign
————1
Benign
————3
Total—123

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

UBE2L3 · 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
UBE2L3 expression in human gastric cancer and its clinical significance.
Zhang X et al.·J Cancer Res Clin Oncol
2024
New developments in genetics of myositis.
Rothwell S et al.·Curr Opin Rheumatol
2016Review
UBE2L3 promotes squamous cell carcinoma progression in the oral cavity and hypopharynx via activating the NF-κB signaling by increasing IκBα degradation.
Cui Z et al.·Cell Biol Int
2022
A functional haplotype of UBE2L3 confers risk for systemic lupus erythematosus.
Wang S et al.·Genes Immun
2012Functional
UBE2L3, a susceptibility gene that plays oncogenic role in hepatitis B-related hepatocellular carcinoma.
Liu Y et al.·J Viral Hepat
2018
The haplotype of UBE2L3 gene is associated with Hashimoto's thyroiditis in a Chinese Han population.
Wang Y et al.·BMC Endocr Disord
2016
Overexpression of ubiquitin-conjugating enzyme E2 L3 in hepatocellular carcinoma potentiates apoptosis evasion by inhibiting the GSK3β/p65 pathway.
Tao NN et al.·Cancer Lett
2020
Host genetic variants influencing the clinical course of hepatitis B virus infection.
Matsuura K et al.·J Med Virol
2016Review
Diagnosis of celiac disease on a gluten-free diet: a multicenter prospective quasi-experimental clinical study.
Gómez-Aguililla S et al.·BMC Med
2025
Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer.
Li JD et al.·BMC Cancer
2022Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Single cell transcriptomics of human psoriasis and epidermal specific Ube2l3 deficient mice highlight CXCL16/CXCR6 involvement in psoriasis development.
Chen XY et al.·Nat Commun
2025🔓 Open Access
Interfering with UBE2L3 expression targets regulation of MLKL to promote necroptosis inhibition of growth in osteosarcoma.
Zhao X et al.·World J Surg Oncol
2025🔓 Open Access
Systematic Analysis of E3 Ligase-Related Genes Identified UBE2L3 as a Prognostic Biomarker Associated With Drug Resistance in Acute Myeloid Leukemia.
Ling C et al.·Int J Gen Med
2025🔓 Open Access
UBE2L3 Suppresses Oxidative Stress-regulated Necroptosis to Accelerate Osteosarcoma Progression.
Zhao X et al.·Recent Pat Anticancer Drug Discov
2025
UBE2L3 promotes benzene-induced hematotoxicity via autophagy-dependent ferroptosis.
Wang B et al.·Ecotoxicol Environ Saf
2024
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