GeneBe

ZEB1

protein-coding

zinc finger E-box binding homeobox 1, the group of Zinc fingers C2H2-type|ZF class homeoboxes and pseudogenes

Gene summary

This gene encodes a zinc finger transcription factor. The encoded protein likely plays a role in transcriptional repression of interleukin 2. Mutations in this gene have been associated with posterior polymorphous corneal dystrophy-3 and late-onset Fuchs endothelial corneal dystrophy. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2010]

Previous symbols:
  • TCF8
  • PPCD3

MANE transcript

NM_001174096.2

Inheritance

AD

ClinVar variants

P:35U:129B:38

Top phenotype

Corneal dystrophy, Fuchs endothelial 6; Corneal dystrophy, posterior polymorphous, 3

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr10:31,318,495-31,529,814

External References & Databases

Ensembl (ENSG00000148516)NCBI Gene (6935)OMIM (189909)HGNC:11642GenCCUniProt (P37275)AlphaFoldClinVar (ZEB1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~211.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

posterior polymorphous corneal dystrophy 3STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012200

Submitter: Labcorp Genetics (formerly Invitae)

corpus callosum, agenesis ofMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0009022

Submitter: PanelApp Australia

posterior polymorphous corneal dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020364

Submitter: Orphanet

Fuchs' endothelial dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0005321

Submitter: Orphanet

corneal dystrophy, Fuchs endothelial, 6LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013206

Submitter: G2P

posterior polymorphous corneal dystrophy 3DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0012200

Submitter: G2P

corneal dystrophy, Fuchs endothelial, 6STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013206

Submitter: PanelApp Australia

posterior polymorphous corneal dystrophy 3STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012200

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Corneal dystrophy, Fuchs endothelial 6; Corneal dystrophy, posterior polymorphous, 3AD

Manifestation: Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 12654361; 16252232; 20036349; 21067486; 22199242; 23599324; 23662738; 23807282; 26622166Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZEB1 variants in ClinVar

11 Conditions Cataloged
Inborn genetic diseasesTotal: 114
not providedTotal: 78
Corneal dystrophy, Fuchs endothelial, 6Total: 12
Posterior polymorphous corneal dystrophy 3Total: 11
ZEB1-related disorderTotal: 7
not specifiedTotal: 5
Corneal dystrophyTotal: 4
Posterior polymorphous corneal dystrophyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001174096.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
15
clinvar
7
clinvar
 23
missense
1
clinvar
126
clinvar
11
clinvar
5
clinvar
 143
nonsense
10
clinvar
2
clinvar
 12
start loss
1
clinvar
2
clinvar
 3
frameshift
11
clinvar
7
clinvar
2
clinvar
 20
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total23121292612202

Highest pathogenic variant AF is 0.000007435064

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 81 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001174096.2RefSeqNP_001167567.19MANE Select
ENST00000424869.6EnsemblENSP00000415961.29MANE Select
NM_001128128.3RefSeqNP_001121600.19Standard
NM_001174093.2RefSeqNP_001167564.18Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
zeb1aDanio rerio

Structure: intestine

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Prostate cancer - Homo sapiens (human)
  • MicroRNAs in cancer - Homo sapiens (human)
  • Transcriptional misregulation in cancer - Homo sapiens (human)
  • Diuretics Pathway, Pharmacodynamics
  • miR-targeted genes in leukocytes - TarBase

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • regulation of transcription by RNA polymerase II
  • immune response
  • pattern specification process
  • central nervous system development

Molecular Function

  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • DNA-binding transcription repressor activity, RNA polymerase II-specific
  • chromatin binding
  • DNA-binding transcription factor activity
  • transcription coactivator activity

Cellular Component

  • nucleus
  • nucleoplasm
  • transcription factor complex
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000361642
Coding exons
9
Length
211319
Individuals with no LoFs
125705
Homozygous LoFs
0
Heterozygous LoFs
7
Defined
125712
p
0.0000278
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.604655730.8110.00002897411
Missense (PolyPhen)161245.060.656983086
Synonymous0.7281982110.9360.00001102115
Loss of Function4.96741.40.1690.00000208574

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.0000550.000054rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1. Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5'-CANNTG-3'). Promotes tumorigenicity by repressing stemness-inhibiting microRNAs. {ECO:0000269|PubMed:19935649, ECO:0000269|PubMed:20175752, ECO:0000269|PubMed:20418909}.;
Disease
DISEASE: Corneal dystrophy, Fuchs endothelial, 6 (FECD6) [MIM:613270]: A corneal disease caused by loss of endothelium of the central cornea. It is characterized by focal wart-like guttata that arise from Descemet membrane and develop in the central cornea, epithelial blisters, reduced vision and pain. Descemet membrane is thickened by abnormal collagenous deposition. {ECO:0000269|PubMed:20036349, ECO:0000269|PubMed:23599324, ECO:0000269|PubMed:25190660}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.347

Intolerance Scores

LoFtool
0.445
RVIS EVS
0.56
RVIS percentile EVS
81.67

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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