ZEB2 Gene (Zinc Finger E-Box Binding Homeobox 2)
Transcriptional repressor involved in epithelial-mesenchymal transition, neural crest development, and Mowat-Wilson syndrome
Gene Information Card
| Symbol | ZEB2 |
|---|---|
| Full Name | Zinc Finger E-Box Binding Homeobox 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q22.3 |
| NCBI Gene ID | 9839 ncbi.nlm.nih.gov/gene/9839 |
| Ensembl ID | ENSG00000169554 |
| UniProt ID | O60315 |
| OMIM ID | 605802 |
| HGNC ID | 14881 |
| Aliases | ZFHX1B, SIP1, SMADIP1, HSPC082, KIAA0569 |
Description
ZEB2 (Zinc Finger E-Box Binding Homeobox 2) encodes a transcriptional repressor that binds to E-box sequences and interacts with SMAD proteins. It plays a critical role in epithelial-mesenchymal transition (EMT), neural crest development, and neurogenesis. Heterozygous loss-of-function mutations cause Mowat-Wilson syndrome, characterized by intellectual disability, distinctive facial features, and Hirschsprung disease. ZEB2 is also implicated in cancer metastasis and fibrosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mowat-Wilson syndrome | Heterozygous loss-of-function mutations (nonsense, frameshift, deletions) lead to haploinsufficiency of ZEB2, disrupting neural crest and brain development. | OMIM #235730; ClinVar; PMID: 11528396 |
| Hirschsprung disease | ZEB2 mutations impair enteric neural crest cell migration and differentiation, causing aganglionosis of the distal colon. | OMIM #235730; PMID: 11528396 |
| Colorectal cancer | ZEB2 overexpression promotes EMT and metastasis by repressing E-cadherin expression. | COSMIC; PMID: 17934462 |
| Breast cancer | ZEB2 upregulation correlates with invasive phenotype and poor prognosis via EMT induction. | COSMIC; PMID: 20010872 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 4.2 | Low |
| Kidney | 7.8 | Low |
| Placenta | 9.4 | Low |
| Skeletal muscle | 3.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney; moderate expression |
| HeLa | 8.7 | Cervical carcinoma; low expression |
| MCF7 | 5.4 | Breast cancer; low expression |
| SH-SY5Y | 22.1 | Neuroblastoma; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2083C>T (p.Arg695*) | Nonsense | ~30% of Mowat-Wilson syndrome cases | Loss of function; premature truncation |
| c.2761delC (p.Leu921Trpfs*12) | Frameshift deletion | ~10% of Mowat-Wilson syndrome cases | Loss of function; frameshift and truncation |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein translation |
| Whole gene deletion | Copy number loss | ~5% of Mowat-Wilson syndrome cases | Loss of function; haploinsufficiency |
Mutation functional classification
Loss of Function (LOF)
Majority of ZEB2 mutations in Mowat-Wilson syndrome are loss-of-function (nonsense, frameshift, deletions) leading to haploinsufficiency.
Gain of Function (GOF)
Not reported in germline; overexpression in cancer is considered oncogenic but not due to activating mutations.
Dominant Negative (DN)
Not described for ZEB2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Epithelial-to-mesenchymal transition (EMT) – ZEB2 represses CDH1 (E-cadherin) expression
• TGF-beta signaling pathway – ZEB2 interacts with SMAD proteins
• Neural crest differentiation – ZEB2 regulates SOX10 and other neural crest genes
Protein Summary
ZEB2 is a 1214-amino acid protein containing two zinc finger clusters and a homeodomain. It functions as a transcriptional repressor by binding to E-box sequences (CACCTG) in target gene promoters. ZEB2 interacts with SMAD proteins (SMAD1, SMAD2, SMAD3) and recruits co-repressors such as CtBP. It is a master regulator of EMT, repressing epithelial markers (e.g., E-cadherin) and activating mesenchymal genes. In development, ZEB2 is essential for neural crest cell migration, brain development, and enteric nervous system formation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZEB2 Knockout HEK293 Cell Line | EDJ-KQ6772 | Human | 9839 | Details Get a Quote |
| ZEB2 Knockout A-549 Cell Line | EDJ-KQ31222 | Human | 9839 | Details Get a Quote |
| ZEB2 Knockout HeLa Cell Line | EDJ-KQ31223 | Human | 9839 | Details Get a Quote |
| ZEB2 Knockout HCT 116 Cell Line | EDJ-KQ72202 | Human | 9839 | Details Get a Quote |
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