ZYG11B

Chr 1

zyg-11 family member B, cell cycle regulator

Also known as: ZYG11

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.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.25
Clinical SummaryZYG11B
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
10 unique Pathogenic / Likely Pathogenic· 58 VUS of 99 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.25LOEUF
pLI 0.998
Z-score 4.97
OE 0.11 (0.050.25)
Highly constrained

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

Missense Constraint
3.98Z-score
OE missense 0.44 (0.390.50)
176 obs / 400.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.11 (0.050.25)
00.351.4
Missense OE0.44 (0.390.50)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 4 / 36.3Missense obs/exp: 176 / 400.3Syn Z: -0.97

ClinVar Variant Classifications

99 submitted variants in ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic4
VUS58
Likely Benign3
6
Pathogenic
4
Likely Pathogenic
58
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
1
0
3
0
4
VUS
0
54
4
0
58
Likely Benign
0
0
3
0
3
Benign
0
0
0
0
0
Total15416071

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

View in ClinVar →

Protein Context — Lollipop Plot

ZYG11B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗