ZYG11B

Chr 1

zyg-11 family member B, cell cycle regulator

Also known as: ZYG11

NCBI Gene: 79699 ENSG00000162378 UniProt: Q9C0D3 OMIM: 618673

The ZYG11B protein serves as a substrate adapter in an E3 ubiquitin ligase complex that targets proteins with specific N-terminal sequences for degradation, functioning in protein quality control and clearance of cellular fragments. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants, indicating that proper protein dosage is critical for normal development.

OMIM ResearchSummary from RefSeq, UniProt

Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process and protein quality control for misfolded or incompletely synthesized proteins. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.25

Clinical Summary— ZYG11B

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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

1 unique Pathogenic / Likely Pathogenic· 54 VUS of 84 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.25LOEUF

pLI 0.998

Z-score 4.97

OE 0.11 (0.05–0.25)

Highly constrained

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

Missense Constraint?

3.98Z-score

OE missense 0.44 (0.39–0.50)

176 obs / 400.3 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.11 (0.05–0.25)

0≤0.351.4

Missense OE?0.44 (0.39–0.50)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 4 / 36.3Missense obs/exp: 176 / 400.3Syn Z: -0.97

ClinVar Variant Classifications

84 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS54

Likely Benign1

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0	0
Likely Pathogenic	1	0	0	1
VUS	0	54	0	54
Likely Benign	0	0	1	1
Benign	0	0	0	0
Total	1	54	1	56

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap ZYG11B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →