ZEB2

Chr 2

zinc finger E-box binding homeobox 2

Also known as: HSPC082, SIP-1, SIP1, SMADIP1, ZFHX1B

NCBI Gene: 9839ENSG00000169554UniProt: O60315

The protein encoded by this gene is a member of the Zfh1 family of 2-handed zinc finger/homeodomain proteins. It is located in the nucleus and functions as a DNA-binding transcriptional repressor that interacts with activated SMADs. Mutations in this gene are associated with Hirschsprung disease/Mowat-Wilson syndrome. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jan 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMowat-Wilson syndrome

Clinical highlights

Gene-disease validity (ClinGen)
Mowat-Wilson syndrome · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
188
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.11
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — ZEB2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.11LOEUF
pLI 1.000
Z-score 6.03
OE 0.02 (0.01–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
3.94Z-score
OE missense 0.57 (0.52–0.62)
378 obs / 663.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.02 (0.01–0.11)
0≤0.351.4
Missense OE?0.57 (0.52–0.62)
0≤0.61.4
Synonymous OE?1.02
0≤1.21.6
LoF obs/exp: 1 / 44.3Missense obs/exp: 378 / 663.9Syn Z: -0.23

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ZEB2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients