ZMIZ1

Chr 10AD

zinc finger MIZ-type containing 1

Also known as: MIZ, NEDDFSA, RAI17, TRAFIP10, ZIMP10

NCBI Gene: 57178ENSG00000108175UniProt: Q9ULJ6OMIM: 607159

This protein acts as a transcriptional coactivator that regulates multiple signaling pathways including androgen receptor, TGF-beta/SMAD, and NOTCH1, and is involved in pyramidal neuron positioning during cerebral cortex development. Mutations cause neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.251 OMIM phenotype
Clinical Summary— ZMIZ1
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 204 VUS of 400 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.25LOEUF
pLI 0.999
Z-score 5.79
OE 0.13 (0.07–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.39Z-score
OE missense 0.64 (0.59–0.69)
447 obs / 699.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.13 (0.07–0.25)
0≤0.351.4
Missense OE0.64 (0.59–0.69)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 7 / 52.1Missense obs/exp: 447 / 699.1Syn Z: -0.68
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongZMIZ1-related syndromic neurodevelopmental disorderLOFAD
DN
0.3495th %ile
GOF
0.15100th %ile
LOF
0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 85% of P/LP variants are LoF · LOEUF 0.25

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic10
VUS204
Likely Benign138
Benign13
Conflicting4
10
Pathogenic
10
Likely Pathogenic
204
VUS
138
Likely Benign
13
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
0
0
10
Likely Pathogenic
8
1
1
0
10
VUS
2
192
10
0
204
Likely Benign
0
19
42
77
138
Benign
0
11
2
0
13
Conflicting
—4
Total192245577379

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ZMIZ1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Penetrance, variable expressivity and monogenic neurodevelopmental disorders.
de Masfrand S et al.·Eur J Med Genet
2024
Genome-wide association analysis identifies ancestry-specific genetic variation associated with acute response to metformin and glipizide in SUGAR-MGH.
Li JH et al.·Diabetologia
2023
Unraveling the Link between Air Pollution and Psoriasis Subtypes: Genetic Architecture of Epigenetic Insights and Mediating Cytokines.
Leng RX et al.·Environ Sci Technol
2025
Compound Heterozygote of Point Mutation and Chromosomal Microdeletion Involving OTUD6B Coinciding with ZMIZ1 Variant in Syndromic Intellectual Disability.
Phetthong T et al.·Genes (Basel)
2021
The effects of air and transportation noise pollution-related altered blood gene expression, DNA methylation, and protein abundance levels on gastrointestinal diseases risk.
Zhan ZQ et al.·Sci Total Environ
2024
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
ZMIZ1 promotes PAX6 ubiquitination through SMAD3 to drive the malignant progression of acute myeloid leukemia.
Zhou L et al.·Mol Cell Probes
2026
[A fetus with Neurodevelopmental disorders with deformed facial features and distal skeletal abnormalities due to a rare variant of ZMIZ1 gene and literature review].
Zou J et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2026Review
Loss of Zmiz1 in Mice Leads to Impaired Cortical Development and Autistic-Like Behaviors.
K C R et al.·Biol Psychiatry
2026
Genetic and functional analysis of ZMIZ1 in neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies (NEDDFSA): insights from muscle cells and signaling pathways.
Li S et al.·Pediatr Res
2025Functional
Transcriptional coregulator ZMIZ1 modulates estrogen responses that are essential for healthy endometrial function.
Hewitt SC et al.·J Clin Invest
2025Open Access
Top 5 resultsSearch Europe PMC ↗

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