MSTO1

Chr 1ADAR

misato mitochondrial distribution and morphology regulator 1

Also known as: LST005, MMYAT, MST

NCBI Gene: 55154 ENSG00000125459 UniProt: Q9BUK6 OMIM: 617619

The MSTO1 protein regulates mitochondrial distribution and morphology and is required for mitochondrial fusion and network formation. Mutations cause myopathy and ataxia affecting muscle and cerebellar systems, with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene shows minimal constraint against loss-of-function variants (LOEUF 1.076), indicating tolerance to heterozygous loss.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Involved in mitochondrion distribution; mitochondrion organization; and positive regulation of mitochondrial fusion. Located in mitochondrial outer membrane. Is active in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Myopathy, mitochondrial, and ataxiaMIM #617675

ADAR

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · AR · ClinGen 2023

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.08

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.000

Z-score 1.27

OE 0.72 (0.49–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.02Z-score

OE missense 1.00 (0.91–1.11)

262 obs / 261.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.72 (0.49–1.08)

0≤0.351.4

Missense OE?1.00 (0.91–1.11)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 17 / 23.7Missense obs/exp: 262 / 261.0Syn Z: -0.45

Background carrier burden — how many people carry a rare variant somewhere in MSTO1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 74

442 rare PASS variants

Rare truncating (LoF)

1 in 1,900

56 rare PASS variants

Rare synonymous (reference)

1 in 260

156 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MSTO1. 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 140	1 in 2,900
South Asian	~43k	1 in 71	1 in 2,100
Remaining (unassigned)	~30k	1 in 53	1 in 870
European (Finnish)	~27k	1 in 710	≈ 1 in 27,000
Admixed American	~22k	1 in 65	1 in 780
African / African American	~21k	1 in 93	1 in 1,500
East Asian	~20k	1 in 84	1 in 1,000
Ashkenazi Jewish	~13k	1 in 1,200	none seen
Middle Eastern	~2,884	1 in 140	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): 7 of 14 coding exons well covered in gnomAD exomes; exons 1, 2, 3, 6, 14 poorly covered; exons 5, 7 marginal. Genomes: 6 of 14 (exons 1, 2, 3, 4, 5 and 3 more below).? see exons ↓