ZEB1
zinc finger E-box binding homeobox 1, the group of Zinc fingers C2H2-type|ZF class homeoboxes and pseudogenes
Basic information
Region (hg38): 10:31318495-31529814
Previous symbols: [ "TCF8", "PPCD3" ]
Links
Phenotypes
GenCC
Source:
- corneal dystrophy, Fuchs endothelial, 6 (Limited), mode of inheritance: AD
- posterior polymorphous corneal dystrophy 3 (Definitive), mode of inheritance: AD
- posterior polymorphous corneal dystrophy (Supportive), mode of inheritance: AD
- Fuchs' endothelial dystrophy (Supportive), mode of inheritance: AD
- posterior polymorphous corneal dystrophy 3 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Corneal dystrophy, Fuchs endothelial 6; Corneal dystrophy, posterior polymorphous, 3 | AD | General | 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 | Ophthalmologic | 12654361; 16252232; 20036349; 21067486; 22199242; 23599324; 23662738; 23807282; 26622166 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (103 variants)
- not_provided (69 variants)
- Corneal_dystrophy,_Fuchs_endothelial,_6 (11 variants)
- Posterior_polymorphous_corneal_dystrophy_3 (10 variants)
- ZEB1-related_disorder (7 variants)
- not_specified (5 variants)
- Corneal_dystrophy (3 variants)
- Posterior_polymorphous_corneal_dystrophy (2 variants)
- Glaucoma (1 variants)
- Visual_loss (1 variants)
- Posterior_polymorphous_corneal_dystrophy_1 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZEB1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001174096.2. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 14 | 21 | ||||
| missense | 112 | 10 | 128 | |||
| nonsense | 9 | |||||
| start loss | 1 | 2 | 3 | |||
| frameshift | 17 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 19 | 10 | 114 | 24 | 12 |
Highest pathogenic variant AF is 0.00000743506
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ZEB1 | protein_coding | protein_coding | ENST00000361642 | 9 | 211319 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.967 | 0.0334 | 125705 | 0 | 7 | 125712 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.60 | 465 | 573 | 0.811 | 0.0000289 | 7411 |
| Missense in Polyphen | 161 | 245.06 | 0.65698 | 3086 | ||
| Synonymous | 0.728 | 198 | 211 | 0.936 | 0.0000110 | 2115 |
| Loss of Function | 4.96 | 7 | 41.4 | 0.169 | 0.00000208 | 574 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.0000994 | 0.0000993 |
| East Asian | 0.0000545 | 0.0000544 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.0000545 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- 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.;
- Pathway
- 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;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Hypoxia-mediated EMT and Stemness;TGF-beta Signaling Pathway;Pathways in clear cell renal cell carcinoma;Interleukin-4 and 13 signaling;EMT transition in Colorectal Cancer;Hypertrophy Model;sumoylation as a mechanism to modulate ctbp-dependent gene responses;TGF_beta_Receptor;Integrin-linked kinase signaling
(Consensus)
Recessive Scores
- pRec
- 0.347
Intolerance Scores
- loftool
- 0.445
- rvis_EVS
- 0.56
- rvis_percentile_EVS
- 81.67
Haploinsufficiency Scores
- pHI
- 0.482
- hipred
- Y
- hipred_score
- 0.851
- ghis
- 0.522
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Zeb1
- Phenotype
- vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; pigmentation phenotype; neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; reproductive system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; taste/olfaction phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- zeb1a
- Affected structure
- intestine
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- 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;cell population proliferation;negative regulation of cell population proliferation;regulation of mesenchymal cell proliferation;regulation of transforming growth factor beta receptor signaling pathway;cytokine-mediated signaling pathway;regulation of T cell differentiation in thymus;negative regulation of endothelial cell differentiation;positive regulation of neuron differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;embryonic camera-type eye morphogenesis;embryonic skeletal system morphogenesis;semicircular canal morphogenesis;regulation of smooth muscle cell differentiation;cartilage development;cellular response to amino acid stimulus;cochlea morphogenesis
- Cellular component
- nucleus;nucleoplasm;transcription factor complex;cytosol
- 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;transcription corepressor activity;protein binding;transcription factor binding;zinc ion binding;E-box binding