MSTO1

Chr 1ADAR

misato mitochondrial distribution and morphology regulator 1

Also known as: LST005, MMYAT, MST

NCBI Gene: 55154ENSG00000125459UniProt: Q9BUK6

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]

Primary Disease Associations & Inheritance

Myopathy, mitochondrial, and ataxiaMIM #617675
ADAR
260
ClinVar variants
36
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MSTO1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 146 VUS of 260 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.02Z-score
OE missense 1.00 (0.91–1.11)
262 obs / 261.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.72 (0.49–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.91–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 17 / 23.7Missense obs/exp: 262 / 261.0Syn Z: -0.45

ClinVar Variant Classifications

260 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic14
VUS146
Likely Benign47
Benign18
Conflicting11
22
Pathogenic
14
Likely Pathogenic
146
VUS
47
Likely Benign
18
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
18
0
22
Likely Pathogenic
3
6
5
0
14
VUS
3
121
21
1
146
Likely Benign
0
13
13
21
47
Benign
0
7
10
1
18
Conflicting
—11
Total91486723258

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

View in ClinVar →

Protein Context — Lollipop Plot

MSTO1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Myopathy, mitochondrial, and ataxia

MIM #617675

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic overlap between ALS and other neurodegenerative or neuromuscular disorders.
Olsen CG et al.·Amyotroph Lateral Scler Frontotemporal Degener
2024
MSTO1-related mitochondrial myopathy and ataxia syndrome: Case series and literature review.
Sharma R et al.·Neuromuscul Disord
2026Review
Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia.
Nasca A et al.·Hum Mutat
2017
Autosomal recessive pathogenic MSTO1 variants in hereditary optic atrophy.
Gerber S et al.·EMBO Mol Med
2023
A novel case of MSTO1 gene related congenital muscular dystrophy with progressive neurological involvement.
Ardicli D et al.·Neuromuscul Disord
2019Case report
MSTO1 mutations cause mtDNA depletion, manifesting as muscular dystrophy with cerebellar involvement.
Donkervoort S et al.·Acta Neuropathol
2019
Novel biallelic variants in MSTO1 associated with mitochondrial myopathy.
Schultz-Rogers L et al.·Cold Spring Harb Mol Case Stud
2019Case report
Mitochondrial dynamics: Biological roles, molecular machinery, and related diseases.
El-Hattab AW et al.·Mol Genet Metab
2018Review
Whole-exome sequencing identifies rare compound heterozygous mutations in the MSTO1 gene associated with cerebellar ataxia and myopathy.
Li K et al.·Eur J Med Genet
2020
A novel homozygous MSTO1 mutation in Ashkenazi Jewish siblings with ataxia and myopathy.
Nasca A et al.·J Hum Genet
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools