ZEB2

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

Basic information

Region (hg38): 2:144364364-144521057

Previous symbols: [ "ZFHX1B" ]

Links

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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 45.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_014795.4	NP_055610.1	9	yes	-
ENST00000627532.3	ENSP00000487174.1	9	yes	-
NM_001171653.2	NP_001165124.1	8	-	-
ENST00000303660.8	ENSP00000302501.4	9	-	-

Phenotypes

GenCC

Source: genCC

• Mowat-Wilson syndrome (Definitive), mode of inheritance: AD
• Mowat-Wilson syndrome (Definitive), mode of inheritance: AD
• Mowat-Wilson syndrome (Strong), 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 (1274 variants)
• not_provided (379 variants)
• Inborn_genetic_diseases (189 variants)
• not_specified (141 variants)
• ZEB2-related_disorder (50 variants)
• See_cases (5 variants)
• Neurodevelopmental_disorder (3 variants)
• Intellectual_disability (3 variants)
• Marfanoid_habitus_and_intellectual_disability (2 variants)
• Cleft_lip/palate (1 variants)
• Hirschsprung_disease-intellectual_disability_syndrome,_late_infantile (1 variants)
• Neurodevelopmental_delay (1 variants)
• Lennox-Gastaut_syndrome (1 variants)
• Abnormal_brain_morphology (1 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Fetal_akinesia_deformation_sequence_1 (1 variants)
• Megacolon (1 variants)
• Aganglionic_megacolon (1 variants)
• Smith-Magenis_Syndrome-like (1 variants)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus_syndrome_1 (1 variants)
• Arthrogryposis_multiplex_congenita (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. These statistics are base on transcript: NM_014795.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	325	5	338
missense	20	30	483	165	46	744
nonsense	93	14	3			110
start loss			2			2
frameshift	198	28	6			232
splice donor/acceptor (+/-2bp)	12	9	2			23
Total	323	81	504	490	51

Highest pathogenic variant AF is 0.0000020521632

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
		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

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

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