ZMIZ1

Chr 10AD

zinc finger MIZ-type containing 1

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

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomaliesMIM #618659
AD
0
Active trials
28
Pubs (1 yr)
68
P/LP submissions
12%
P/LP missense
0.25
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical SummaryZMIZ1
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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
51 unique Pathogenic / Likely Pathogenic· 195 VUS of 449 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.25LOEUF
pLI 0.999
Z-score 5.79
OE 0.13 (0.070.25)
Highly constrained

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

Missense Constraint
3.39Z-score
OE missense 0.64 (0.590.69)
447 obs / 699.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.13 (0.070.25)
00.351.4
Missense OE0.64 (0.590.69)
00.61.4
Synonymous OE1.05
01.21.6
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 · 47% 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

449 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic27
VUS195
Likely Benign151
Benign24
Conflicting7
24
Pathogenic
27
Likely Pathogenic
195
VUS
151
Likely Benign
24
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
2
15
0
24
Likely Pathogenic
17
4
5
1
27
VUS
3
170
18
4
195
Likely Benign
0
18
46
87
151
Benign
0
13
7
4
24
Conflicting
7
Total272079196428

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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