ZEB1

Chr 10AD

zinc finger E-box binding homeobox 1

Also known as: AREB6, BZP, DELTAEF1, FECD6, NIL2A, PPCD3, TCF8, ZFHEP

NCBI Gene: 6935ENSG00000148516UniProt: P37275

This zinc finger transcription factor acts as a transcriptional repressor, inhibiting interleukin-2 gene expression and regulating epithelial-mesenchymal transition and neuronal differentiation. Mutations cause autosomal dominant corneal dystrophies including Fuchs endothelial corneal dystrophy and posterior polymorphous corneal dystrophy. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Corneal dystrophy, Fuchs endothelial, 6MIM #613270
AD
Corneal dystrophy, posterior polymorphous, 3MIM #609141
AD
3
Active trials
316
Pubs (1 yr)
52
P/LP submissions
9%
P/LP missense
0.32
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical Summary— ZEB1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 130 VUS of 228 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.967
Z-score 4.96
OE 0.17 (0.10–0.32)
Highly constrained

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

Missense Constraint
1.60Z-score
OE missense 0.81 (0.75–0.88)
465 obs / 573.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.10–0.32)
0≤0.351.4
Missense OE0.81 (0.75–0.88)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 7 / 41.4Missense obs/exp: 465 / 573.1Syn Z: 0.73
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveZEB1-related corneal dystrophy, posterior polymorphousLOFAD
limitedZEB1-related corneal dystrophy Fuchs endothelialLOFAD
DN
0.2599th %ile
GOF
0.1999th %ile
LOF
0.80top 5%

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

LOFprediction above median · 40% of P/LP variants are LoF · LOEUF 0.32

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

228 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic12
VUS130
Likely Benign26
Benign18
Conflicting5
31
Pathogenic
12
Likely Pathogenic
130
VUS
26
Likely Benign
18
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
2
19
0
31
Likely Pathogenic
7
2
3
0
12
VUS
2
122
6
0
130
Likely Benign
0
7
5
14
26
Benign
0
5
5
8
18
Conflicting
—5
Total191383822222

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

View in ClinVar →

Protein Context — Lollipop Plot

ZEB1 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients