ZEB2

zinc finger E-box binding homeobox 2, the group of ZF class homeoboxes and pseudogenes|Zinc fingers C2H2-type

Basic information

Region (hg38): 2:144364363-144521057

Previous symbols: [ "ZFHX1B" ]

Links

ENSG00000169554 ∙ NCBI:9839 ∙ OMIM:605802 ∙ HGNC:14881 ∙ Uniprot:O60315 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Mowat-Wilson syndrome (Definitive), mode of inheritance: AD
• Mowat-Wilson syndrome (Strong), mode of inheritance: AD
• Mowat-Wilson syndrome (Definitive), mode of inheritance: AD
• Mowat-Wilson syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mowat-Wilson syndrome	AD	General	The condition can include Hirschsprung disease, among other multi-systemic manifestations; 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	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	9719364; 11448942; 11279515; 14679597; 15121779; 16088920; 16688751; 16532472; 17203459; 19215041;20301585; 21343952; 21497296; 22246645; 22486326; 23322667; 23427518; 23466526; 23523603; 24029077; 24715670; 27831545

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZEB2 gene.

• Mowat-Wilson syndrome (918 variants)
• not provided (309 variants)
• not specified (132 variants)
• Inborn genetic diseases (127 variants)
• ZEB2-related condition (14 variants)
• See cases (4 variants)
• Neurodevelopmental disorder (3 variants)
• Intellectual disability (2 variants)
• Marfanoid habitus and intellectual disability (2 variants)
• Abnormal brain morphology (1 variants)
• Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
• Neurodevelopmental delay (1 variants)
• Abnormality of the nervous system (1 variants)
• Lennox-Gastaut syndrome (1 variants)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (1 variants)
• Smith-Magenis Syndrome-like (1 variants)
• Hirschsprung disease-intellectual disability syndrome, late infantile (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZEB2 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			6	236	5	247
missense	4	20	326	81	30	461
nonsense	76	9	1			86
start loss				1		1
frameshift	139	17	1			157
inframe indel		1	8	1		10
splice donor/acceptor (+/-2bp)	9	4				13
splice region	1		11	15	5	32
non coding		1	21	56	23	101
Total	228	52	363	375	58

Variants in ZEB2

This is a list of pathogenic ClinVar variants found in the ZEB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-144384605-CT-C		Mowat-Wilson syndrome	Benign (Jun 14, 2016)
2-144384605-C-CT		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144384605-C-CTT		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144386925-G-GC		Mowat-Wilson syndrome	Conflicting classifications of pathogenicity (Dec 01, 2022)
2-144386933-C-A			Benign (Jul 01, 2023)
2-144386934-AC-A		Mowat-Wilson syndrome	Likely benign (Jun 14, 2016)
2-144387045-GTA-G		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144387045-G-GTA		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144387045-G-GTATA		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144387045-G-GTATATA		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144387054-T-TAC		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144387062-T-TAC		Mowat-Wilson syndrome	Conflicting classifications of pathogenicity (Mar 01, 2023)
2-144387064-C-T			Likely benign (Mar 01, 2023)
2-144387459-A-G			Likely benign (May 01, 2023)
2-144387466-TA-T		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144387505-CT-C		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144387654-C-CT		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144388331-GCTCTT-G		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144388890-GA-G		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144388890-G-GA		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144388936-GA-G		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144388936-G-GA		Mowat-Wilson syndrome	Uncertain significance (Jun 14, 2016)
2-144389415-G-GA		Mowat-Wilson syndrome	Likely benign (Jun 14, 2016)
2-144389445-A-C		not specified	Likely benign (Jul 01, 2016)
2-144389456-T-C		Mowat-Wilson syndrome • Inborn genetic diseases	Benign/Likely benign (Dec 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZEB2	protein_coding	protein_coding	ENST00000558170	9	140500

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.99e-7	124846	0	1	124847	0.00000400

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.94	378	664	0.569	0.0000377	8112
Missense in Polyphen		73	211.53	0.34511		2608
Synonymous	-0.233	264	259	1.02	0.0000165	2239
Loss of Function	6.03	1	44.3	0.0226	0.00000251	583

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional inhibitor that binds to DNA sequence 5'- CACCT-3' in different promoters. Represses transcription of E- cadherin. {ECO:0000269|PubMed:16061479}.
• Disease: DISEASE: Mowat-Wilson syndrome (MOWS) [MIM:235730]: A complex developmental disorder characterized by mental retardation, delayed motor development, epilepsy, microcephaly and a wide spectrum of clinically heterogeneous features suggestive of neurocristopathies at the cephalic, cardiac, and vagal levels. Affected patients show an easily recognizable facial appearance with deep set eyes and hypertelorism, medially divergent, broad eyebrows, prominent columella, pointed chin and uplifted, notched ear lobes. Some patients manifest Hirschsprung disease. {ECO:0000269|PubMed:11448942, ECO:0000269|PubMed:12451214, ECO:0000269|PubMed:15384097, ECO:0000269|PubMed:16688751}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: MicroRNAs in cancer - Homo sapiens (human);TGF-beta Signaling Pathway;EMT transition in Colorectal Cancer;TGF-beta Receptor Signaling;TGF_beta_Receptor (Consensus)

Recessive Scores

• pRec: 0.223

Intolerance Scores

• loftool: 0.0187
• rvis_EVS: -0.91
• rvis_percentile_EVS: 10.03

Haploinsufficiency Scores

• pHI: 0.894
• hipred: Y
• hipred_score: 0.825
• ghis: 0.550

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.960

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Zeb2
• 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); growth/size/body region phenotype; craniofacial phenotype; cellular phenotype; embryo phenotype; 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); reproductive system phenotype; pigmentation 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); vision/eye phenotype

Zebrafish Information Network

• Gene name: zeb2b
• Affected structure: intrahepatic bile duct
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;neural crest cell migration;somitogenesis;neural tube closure;nervous system development;corpus callosum morphogenesis;hippocampus development;cell proliferation in forebrain;corticospinal tract morphogenesis;positive regulation of Wnt signaling pathway;positive regulation of JUN kinase activity;positive regulation of melanocyte differentiation;positive regulation of transcription by RNA polymerase II;positive regulation of melanin biosynthetic process;developmental pigmentation;collateral sprouting;positive regulation of axonogenesis;mammillary axonal complex development;melanocyte migration;positive regulation of lens fiber cell differentiation;regulation of melanosome organization
• Cellular component: nuclear chromatin;nucleus;nucleolus;cytosol
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding;phosphatase regulator activity;sequence-specific DNA binding;metal ion binding;R-SMAD binding