UBE4B

Chr 1

ubiquitination factor E4B

NCBI Gene: 10277 ENSG00000130939 UniProt: O95155 OMIM: 613565

Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases (By similarity). May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase (By similarity). May regulate myosin assembly in striated muscles together with STUB1 and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (PubMed:17369820)

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.16

Clinical Summary— UBE4B

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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.

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ClinVar Variants

130 VUS of 182 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.16LOEUF

pLI 1.000

Z-score 7.02

OE 0.07 (0.04–0.16)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.73Z-score

OE missense 0.62 (0.58–0.67)

488 obs / 781.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.07 (0.04–0.16)

0≤0.351.4

Missense OE?0.62 (0.58–0.67)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 5 / 67.0Missense obs/exp: 488 / 781.0Syn Z: 0.68

This gene — mechanism propensity

0.2898th %ile

GOF

0.3689th %ile

LOF

0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.16

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

182 submitted variants in ClinVar

ClinVar

Classification Summary

VUS130

Likely Benign9

Benign6

130

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	128	0	0	130
Likely Benign	0	2	4	3	9
Benign	0	2	2	2	6
Total	2	132	6	5	145

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

View in ClinVar →

35 pathogenic / likely-pathogenic (of 46) ClinVar copy-number / structural variants overlap UBE4B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →