ZEB1

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

Basic information

Region (hg38): 10:31318494-31529814

Previous symbols: [ "TCF8", "PPCD3" ]

Links

ENSG00000148516 ∙ NCBI:6935 ∙ OMIM:189909 ∙ HGNC:11642 ∙ Uniprot:P37275 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the ZEB1 gene.

• not provided (46 variants)
• Inborn genetic diseases (31 variants)
• Corneal dystrophy, Fuchs endothelial, 6 (5 variants)
• Corneal dystrophy (3 variants)
• Posterior polymorphous corneal dystrophy 3;Corneal dystrophy, Fuchs endothelial, 6 (2 variants)
• not specified (2 variants)
• Polymorphous corneal dystrophy;Visual loss;Glaucoma (1 variants)
• Posterior polymorphous corneal dystrophy 3 (1 variants)
• Posterior polymorphous corneal dystrophy 1 (1 variants)
• Polymorphous corneal dystrophy (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	4	11
missense			36	4	5	45
nonsense	3	1				4
start loss	1					1
frameshift	6	5	1			12
inframe indel				1	2	3
splice donor/acceptor (+/-2bp)		1				1
splice region			1	1		2
non coding					2	2
Total	10	7	37	12	13

Highest pathogenic variant AF is 0.00000657

Variants in ZEB1

This is a list of pathogenic ClinVar variants found in the ZEB1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-31319235-A-C		Posterior polymorphous corneal dystrophy 3	Pathogenic (Jan 23, 2023)
10-31319237-G-A		Corneal dystrophy, Fuchs endothelial, 6;Posterior polymorphous corneal dystrophy 3	Pathogenic (Apr 20, 2016)
10-31461077-AGAT-A			Benign (Jan 18, 2024)
10-31461116-T-C			Likely benign (Sep 20, 2022)
10-31461136-G-C			Uncertain significance (Sep 20, 2022)
10-31461160-T-G		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
10-31461170-C-T			Benign (Jan 12, 2024)
10-31461187-G-A		Inborn genetic diseases	Uncertain significance (Sep 14, 2023)
10-31461198-G-A		Inborn genetic diseases	Uncertain significance (Feb 13, 2024)
10-31461211-A-C		Corneal dystrophy, Fuchs endothelial, 6 • not specified • ZEB1-related disorder	Benign/Likely benign (Dec 24, 2023)
10-31461220-A-G			Benign (Apr 01, 2022)
10-31495857-C-T			Likely benign (Jan 05, 2024)
10-31502356-G-A		Inborn genetic diseases	Uncertain significance (Nov 27, 2023)
10-31502365-G-C		Inborn genetic diseases	Uncertain significance (Mar 04, 2024)
10-31502384-A-G		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
10-31502425-C-T			Pathogenic (Aug 31, 2022)
10-31502453-C-T		Inborn genetic diseases	Uncertain significance (Jun 28, 2023)
10-31502492-G-T		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
10-31502506-AAT-A			Pathogenic (Apr 14, 2023)
10-31510680-A-G			Likely benign (Jun 04, 2018)
10-31510691-CA-C		Corneal dystrophy, Fuchs endothelial, 6	Likely pathogenic (Oct 16, 2018)
10-31510766-G-A		Inborn genetic diseases	Uncertain significance (Mar 29, 2022)
10-31510794-T-C			Benign (Oct 08, 2023)
10-31510810-T-G		Inborn genetic diseases	Uncertain significance (Apr 25, 2023)
10-31510810-T-TA		Polymorphous corneal dystrophy	Likely pathogenic (Nov 17, 2020)

GnomAD

Source: gnomAD

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: 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.
• 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