UBE2J2

Chr 1

ubiquitin conjugating enzyme E2 J2

Also known as: NCUBE-2, NCUBE2, PRO2121, UBC6

The UBE2J2 protein is an E2 ubiquitin-conjugating enzyme located in the endoplasmic reticulum membrane that catalyzes ubiquitin attachment to misfolded proteins, facilitating their degradation through the endoplasmic reticulum-associated degradation (ERAD) pathway. Mutations cause autosomal recessive intellectual disability with epilepsy and brain abnormalities, typically presenting in infancy or early childhood. The gene is highly constrained against loss-of-function variants (pLI 0.91, LOEUF 0.39), indicating that complete loss of protein function is likely pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
138
P/LP submissions
0%
P/LP missense
0.39
LOEUF
Mechanism
Clinical SummaryUBE2J2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
131 unique Pathogenic / Likely Pathogenic· 38 VUS of 189 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.39LOEUF
pLI 0.910
Z-score 2.96
OE 0.08 (0.030.39)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.79Z-score
OE missense 0.61 (0.520.72)
100 obs / 164.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.030.39)
00.351.4
Missense OE0.61 (0.520.72)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 1 / 12.1Missense obs/exp: 100 / 164.7Syn Z: -0.21

ClinVar Variant Classifications

189 submitted variants in ClinVar

Classification Summary

Pathogenic124
Likely Pathogenic7
VUS38
Likely Benign1
124
Pathogenic
7
Likely Pathogenic
38
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
124
0
124
Likely Pathogenic
0
0
7
0
7
VUS
0
19
19
0
38
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total0191510170

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

View in ClinVar →

Protein Context — Lollipop Plot

UBE2J2 · 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

No active trials found for this gene.

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Clinical Literature
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