UBR2

Chr 6

ubiquitin protein ligase E3 component n-recognin 2

Also known as: C6orf133, bA49A4.1, dJ242G1.1, dJ392M17.3

NCBI Gene: 23304ENSG00000024048UniProt: Q8IWV8

Enables L-leucine binding activity and ubiquitin protein ligase activity. Involved in several processes, including cellular response to L-leucine; protein K63-linked ubiquitination; and regulation of signal transduction. Predicted to be located in cytosol. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

211
ClinVar variants
9
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— UBR2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 181 VUS of 211 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.21LOEUF
pLI 1.000
Z-score 8.33
OE 0.14 (0.09–0.21)
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.
3.15Z-score
OE missense 0.71 (0.66–0.76)
651 obs / 919.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.14 (0.09–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.66–0.76)
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.0.98
0≤1.21.6
LoF obs/exp: 15 / 108.6Missense obs/exp: 651 / 919.4Syn Z: 0.25

ClinVar Variant Classifications

211 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
VUS181
Likely Benign19
Benign2
9
Pathogenic
181
VUS
19
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
8
0
9
Likely Pathogenic
0
0
0
0
0
VUS
0
178
3
0
181
Likely Benign
0
7
7
5
19
Benign
0
0
0
2
2
Total1185187211

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

View in ClinVar →

Protein Context — Lollipop Plot

UBR2 · 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
📖
GeneReview available — UBR2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Exploration of novel mechanisms of azole resistance in Candida auris.
Li J et al.·Antimicrob Agents Chemother
2024Functional
UBR2 of the N-end rule pathway is required for chromosome stability via histone ubiquitylation in spermatocytes and somatic cells.
An JY et al.·PLoS One
2012
Screening of targeted panel genes in Brazilian patients with primary ovarian insufficiency.
França MM et al.·PLoS One
2020Cohort
Single nucleotide polymorphism in the UBR2 gene may be a genetic risk factor for Japanese patients with azoospermia by meiotic arrest.
Miyamoto T et al.·J Assist Reprod Genet
2011Cohort
Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia.
Judge SM et al.·BMC Cancer
2014
The transcription factor Rpn4 activates its own transcription and induces efflux pump expression to confer fluconazole resistance in Candida auris.
Chow EWL et al.·mBio
2023
UBR7 functions with UBR5 in the Notch signaling pathway and is involved in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism.
Li C et al.·Am J Hum Genet
2021
Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease.
Vilariño-Güell C et al.·PLoS Genet
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
An alternative pocket for binding the N-degrons by the UBR1 and UBR2 ubiquitin E3 ligases.
Huang ST et al.·Protein Sci
2025🔓 Open Access
The role of UBR2 in triple-negative breast cancer and its implications for immune checkpoint blockade therapy.
Jiang Y et al.·Discov Oncol
2025🔓 Open Access
Upregulation of E3 ligase UBR2 in acetaldehyde-treated C2C12 myotubes and its potential involvement in fast-twitch muscle atrophy in alcohol-fed rats.
Shintani-Ishida K et al.·Alcohol Clin Exp Res (Hoboken)
2025
Saccharomyces cerevisiae Mub1, a substrate adaptor of E3 ubiquitin ligase Ubr2, modulates sensitivity to cell wall stressors through multiple transcription factors.
Šupljika N et al.·FEBS J
2025🔓 Open Access
The phosphatase DUSP22 inhibits UBR2-mediated K63-ubiquitination and activation of Lck downstream of TCR signalling.
Shih YC et al.·Nat Commun
2024🔓 Open Access
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