UBE2F

Chr 2

ubiquitin conjugating enzyme E2 F (putative)

Also known as: NCE2

UBE2F encodes a NEDD8 conjugating enzyme that catalyzes the covalent attachment of NEDD8 to cullins, particularly cullin-5, which is essential for proper protein degradation pathways. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in early infancy, characterized by severe intellectual disability, refractory seizures, and progressive microcephaly. The gene is highly constrained against loss-of-function variants, reflecting its critical role in cellular protein regulation.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
8
Pubs (1 yr)
83
P/LP submissions
0%
P/LP missense
0.38
LOEUF
Mechanism
Clinical SummaryUBE2F
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
81 unique Pathogenic / Likely Pathogenic· 25 VUS of 108 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.38LOEUF
pLI 0.923
Z-score 3.03
OE 0.08 (0.030.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.33Z-score
OE missense 0.64 (0.530.78)
69 obs / 107.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.030.38)
00.351.4
Missense OE0.64 (0.530.78)
00.61.4
Synonymous OE0.70
01.21.6
LoF obs/exp: 1 / 12.6Missense obs/exp: 69 / 107.9Syn Z: 1.48

ClinVar Variant Classifications

108 submitted variants in ClinVar

Classification Summary

Pathogenic79
Likely Pathogenic2
VUS25
79
Pathogenic
2
Likely Pathogenic
25
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
79
0
79
Likely Pathogenic
0
0
2
0
2
VUS
0
16
9
0
25
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total016900106

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

View in ClinVar →

Protein Context — Lollipop Plot

UBE2F · 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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