MZT1

Chr 13

mitotic spindle organizing protein 1

Also known as: C13orf37, MOZART1

NCBI Gene: 440145 ENSG00000204899 UniProt: Q08AG7

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.

ResearchSummary from RefSeq, UniProt

Involved in gamma-tubulin complex localization. Located in centrosome and spindle. Part of gamma-tubulin ring complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.71

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.71LOEUF

pLI 0.046

Z-score 0.59

OE 0.64 (0.26–1.71)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.20Z-score

OE missense 0.92 (0.72–1.18)

44 obs / 47.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.26–1.71)

0≤0.351.4

Missense OE?0.92 (0.72–1.18)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 2 / 3.1Missense obs/exp: 44 / 47.9Syn Z: 0.47

Background carrier burden — how many people carry a rare variant somewhere in MZT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 780

104 rare PASS variants

Rare truncating (LoF)

1 in 8,200

23 rare PASS variants

Rare synonymous (reference)

1 in 570

41 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MZT1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 880	1 in 12,000
South Asian	~43k	1 in 1,300	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 790	1 in 4,200
European (Finnish)	~27k	≈ 1 in 13,000	≈ 1 in 26,000
Admixed American	~22k	1 in 670	≈ 1 in 20,000
African / African American	~21k	1 in 440	≈ 1 in 4,900
East Asian	~20k	1 in 860	none seen
Ashkenazi Jewish	~13k	1 in 640	≈ 1 in 13,000
Middle Eastern	~2,881	≈ 1 in 700	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 3 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 3.? see exons ↓