MZT1

Chr 13

mitotic spindle organizing protein 1

Also known as: C13orf37, MOZART1

The protein is required for recruitment and assembly of the gamma-tubulin ring complex at the centrosome, which regulates microtubule nucleation critical for centrosome duplication and spindle formation. Mutations cause autosomal recessive primary microcephaly with seizures, developmental delay, and intellectual disability. The gene shows low constraint to loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.71
Clinical SummaryMZT1
Population Constraint (gnomAD)
Low constraint (pLI 0.05) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.71LOEUF
pLI 0.046
Z-score 0.59
OE 0.64 (0.261.71)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.20Z-score
OE missense 0.92 (0.721.18)
44 obs / 47.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.64 (0.261.71)
00.351.4
Missense OE0.92 (0.721.18)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 2 / 3.1Missense obs/exp: 44 / 47.9Syn Z: 0.47
DN
0.7131th %ile
GOF
0.78top 25%
LOF
0.3549th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MZT1 · 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

No active trials found for this gene.

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Clinical Literature
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