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ZEB2

zinc finger E-box binding homeobox 2

The ZEB2 gene provides instructions for a protein vital for embryonic development, playing a key role in the formation of various organs and tissues before birth. The ZEB2 gene is essential for proper development, as it encodes a protein that functions as a transcription factor.

Chromosome 2q22.3 Autosomal dominant HGNC:14881 Tier C
ZEB2 2q22.3 p arm q arm 2

ZEB2 is located on the long (q) arm of chromosome 2, at band 2q22.3. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 2 in the library →

Overview

The ZEB2 gene, also known as zinc finger E-box binding homeobox 2, is crucial for early human development. It provides instructions for making a protein that acts as a transcription factor, controlling the expression of other genes involved in forming various organs and tissues.

Disruptions in the ZEB2 gene's function are associated with developmental disorders, such as Mowat-Wilson syndrome.

What the gene does

The protein encoded by the ZEB2 gene is a transcription factor, meaning it binds to specific DNA regions to regulate gene activity. This regulatory role is fundamental during foetal development, impacting the formation of numerous tissues and organs.

It is particularly important for neural crest development, a group of embryonic cells that give rise to parts of the nervous system, endocrine glands, pigment cells, and tissues in the heart, face, and skull. Beyond neural crest derivatives, the ZEB2 protein also influences the development of the digestive tract, skeletal muscles, and kidneys.

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Chromosome location

The ZEB2 gene is located on chromosome 2, specifically at position 2q22.3. This precise genomic location helps define its place within the human genome and its association with specific inherited conditions.

Protein structure

The ZEB2 protein, comprising 1214 amino acids, features several distinct domains. It includes a disordered region at amino acids 1-101 and multiple C2H2-type zinc finger domains: C2H2-type 1 (211-234), C2H2-type 2 (241-263), C2H2-type 3 (282-304), C2H2-type 4; atypical (310-334), C2H2-type 5; atypical (581-605), C2H2-type 6 (999-1021), C2H2-type 7 (1027-1049), and C2H2-type 8; atypical (1055-1076). Additionally, the protein contains a SMAD-MH2 binding domain (437-487) and an atypical Homeobox domain (644-703). Further disordered regions are found at 702-740, 771-810, 832-857, and 1117-1214.

Domain map · 1,214 amino acids
C2H2-type 1 (211–234)C2H2-type 2 (241–263)C2H2-type 3 (282–304)C2H2-type 4; atypical (310–334)C2H2-type 5; atypical (581–605)C2H2-type 6 (999–1021)C2H2-type 7 (1027–1049)C2H2-type 8; atypical (1055–1076)C2H2-type 1211–234C2H2-type 4; atypical310–334C2H2-type 5; atypical581–6051~6071,214
Zinc finger - zinc-binding structural motif
🧬 Explore 3D structure on AlphaFold
UniProt:O60315Length:1,214 aaStructure:AlphaFold

Key variants

Variants in the ZEB2 gene can lead to changes in the structure or function of the encoded protein, often affecting its ability to properly regulate gene expression during development. These genetic changes are typically identified through genetic testing.

1,607
Total variants catalogued in ClinVar
View all on ClinVar →
396 Pathogenic / Likely pathogenic 520 Uncertain significance 587 Benign / Likely benign 104 Conflicting or other

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1027C>T
single nucleotide variant
 p.Arg343Ter Pathogenic ★★☆☆ Mowat-Wilson syndrome
c.1052del
Deletion
 p.Gly351fs Pathogenic ★★☆☆ Mowat-Wilson syndrome
c.1102C>T
single nucleotide variant
 p.Gln368Ter Pathogenic ★★☆☆ not provided
c.1381C>T
single nucleotide variant
 p.Gln461Ter Pathogenic ★★☆☆ not provided
c.1387del
Deletion
 p.Val463fs Pathogenic ★★☆☆ Mowat-Wilson syndrome
c.1426dup
Duplication
 p.Met476fs Pathogenic ★★☆☆ Mowat-Wilson syndrome
c.1489C>T
single nucleotide variant
 p.Gln497Ter Pathogenic ★★☆☆ Mowat-Wilson syndrome
c.1541del
Deletion
 p.Pro514fs Pathogenic ★★☆☆ not provided
c.1843C>T
single nucleotide variant
 p.Gln615Ter Pathogenic ★★☆☆ Mowat-Wilson syndrome
c.1910C>A
single nucleotide variant
 p.Ser637Ter Pathogenic ★★☆☆ Mowat-Wilson syndrome

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the ZEB2 gene are primarily associated with Mowat-Wilson syndrome, an inherited condition affecting multiple body systems. This syndrome often involves developmental delay, intellectual disability, and characteristic facial features, among other issues.

Inheritance pattern

Conditions caused by pathogenic ZEB2 variants typically follow autosomal dominant inheritance.

♀ Affected parent 1 altered copy ♂ Unaffected parent 2 typical copies Affected Unaffected Unaffected Affected Affected Carrier Unaffected Circles = females · Squares = males

Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.

UK clinical status

The ZEB2 gene is included in several NHS Genomic Medicine Service approved panels, indicating its clinical relevance in the UK. It is reviewed in panels for Clefting, DDG2P (Developmental Disorders Genotype-Phenotype Database), Early onset or syndromic epilepsy, Familial Hirschsprung Disease, Foetal anomalies (R21), Intellectual disability, Paediatric pseudo-obstruction syndrome (R438), Rare syndromic craniosynostosis or isolated multisuture synostosis (R100), Severe microcephaly (R88), and Structural eye disease (R36).

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Fetal anomalies · R21 NHS GMS → Paediatric pseudo-obstruction syndrome · R438 NHS GMS → Rare syndromic craniosynostosis or isolated multisuture synostosis · R100 NHS GMS → Severe microcephaly · R88 NHS GMS → Structural eye disease · R36 NHS GMS → Clefting NHS GMS → DDG2P NHS GMS → Early onset or syndromic epilepsy NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary function of the ZEB2 gene?

The ZEB2 gene produces a protein that acts as a transcription factor, controlling the activity of other genes essential for the formation of various organs and tissues during embryonic development.

What condition is most commonly associated with variants in the ZEB2 gene?

Variants in the ZEB2 gene are most commonly associated with Mowat-Wilson syndrome, a genetic disorder characterised by developmental delays, intellectual disability, and distinct facial features.

How does the ZEB2 protein affect foetal development?

The ZEB2 protein is crucial for the proper development of the neural crest, which forms many parts of the nervous system and other body structures, and also influences the formation of the digestive tract, muscles, and kidneys.

References

  1. Yamada Y, Nomura N, Yamada K. The spectrum of ZEB2 mutations causing the Mowat-Wilson syndrome in Japanese populations. American journal of medical genetics. Part A. 2014. PMID: 24715670
  2. Saunders CJ, Zhao W, Ardinger HH. Comprehensive ZEB2 gene analysis for Mowat-Wilson syndrome in a North American cohort: a suggested approach to molecular diagnostics. American journal of medical genetics. Part A. 2009. PMID: 19842203
  3. Dastot-Le Moal F, Wilson M, Mowat D. ZFHX1B mutations in patients with Mowat-Wilson syndrome. Human mutation. 2007. PMID: 17203459
  4. Garavelli L, Mainardi PC. Mowat-Wilson syndrome. Orphanet journal of rare diseases. 2007. PMID: 17958891
  5. Zweier C, Thiel CT, Dufke A. Clinical and mutational spectrum of Mowat-Wilson syndrome. European journal of medical genetics. 2005. PMID: 16053902
  6. Bassez G, Camand OJ, Cacheux V. Pleiotropic and diverse expression of ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the "Mowat-Wilson" syndrome. Neurobiology of disease. 2004. PMID: 15006694
  7. Ishihara N, Yamada K, Yamada Y. Clinical and molecular analysis of Mowat-Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22-q24.1. Journal of medical genetics. 2004. PMID: 15121779
  8. Mowat DR, Wilson MJ, Goossens M. Mowat-Wilson syndrome. Journal of medical genetics. 2003. PMID: 12746390
  9. Adam MP, Bick S, Mirzaa GM. Classic Mowat-Wilson Syndrome. 1993. PMID: 20301585
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 27 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .