MPV17

Chr 2AR

mitochondrial inner membrane protein MPV17

Also known as: CMT2EE, MTDPS6, SYM1

NCBI Gene: 4358ENSG00000115204UniProt: P39210

This gene encodes a mitochondrial inner membrane protein that is implicated in the metabolism of reactive oxygen species. Mutations in this gene have been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDDS). [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, axonal, type 2EEMIM #618400
AR
Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)MIM #256810
AR
402
ClinVar variants
18
Pathogenic / LP
0.00
pLI score
9
Active trials
Clinical Summary— MPV17
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 32 VUS of 402 total submissions
💊
Clinical Trials
9 active or recruiting trials — potential therapeutic options may be available

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.
1.79LOEUF
pLI 0.000
Z-score -0.65
OE 1.20 (0.79–1.79)
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.
0.24Z-score
OE missense 0.93 (0.78–1.11)
89 obs / 95.5 exp
Tolerant

Mild missense constraint

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.1.20 (0.79–1.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.78–1.11)
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.0.95
0≤1.21.6
LoF obs/exp: 14 / 11.6Missense obs/exp: 89 / 95.5Syn Z: 0.26

ClinVar Variant Classifications

402 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic10
VUS32
Likely Benign42
8
Pathogenic
10
Likely Pathogenic
32
VUS
42
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
5
0
8
Likely Pathogenic
6
2
2
0
10
VUS
0
25
7
0
32
Likely Benign
0
0
33
9
42
Benign
0
0
0
0
0
Total92747992

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

View in ClinVar →

Protein Context — Lollipop Plot

MPV17 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MPV17-related mitochondrial DNA depletion syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Charcot-Marie-Tooth disease, axonal, type 2EE

MIM #618400

Molecular basis of disorder known

Autosomal recessive

Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)

MIM #256810

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mitochondrial DNA maintenance defects.
El-Hattab AW et al.·Biochim Biophys Acta Mol Basis Dis
2017Review
Genetic landscape of pediatric acute liver failure of indeterminate origin.
Lenz D et al.·Hepatology
2024
Primary mitochondrial diseases.
Pizzamiglio C et al.·Handb Clin Neurol
2024Review
The role of the Mpv17 protein mutations of which cause mitochondrial DNA depletion syndrome (MDDS): lessons from homologs in different species.
Löllgen S et al.·Biol Chem
2015Review
MPV17-related mitochondrial DNA maintenance defect: New cases and review of clinical, biochemical, and molecular aspects.
El-Hattab AW et al.·Hum Mutat
2018Review
Mitochondrial syndromes with leukoencephalopathies.
Wong LJ·Semin Neurol
2012Review
Novel Variants in MPV17, PRX, GJB1, and SACS Cause Charcot-Marie-Tooth and Spastic Ataxia of Charlevoix-Saguenay Type Diseases.
Zaman Q et al.·Genes (Basel)
2023
Mitochondrial DNA homeostasis impairment and dopaminergic dysfunction: A trembling balance.
Manini A et al.·Ageing Res Rev
2022Review
MPV17 does not control cancer cell proliferation.
Canonne M et al.·PLoS One
2020
Genome-Wide and Rare Variant Association Studies of Amblyopia in the All of Us Research Program.
Lee KAV et al.·Ophthalmology
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Retrospective observational study of the magnetic resonance imaging features of MPV17-related mitochondrial DNA depletion syndrome.
O'Hagan S et al.·Pediatr Radiol
2025🔓 Open Access
Mutation of mpv17 results in loss of iridophores due to mitochondrial dysfunction in tilapia.
Xu J et al.·J Hered
2025
Establishment of a human induced pluripotent stem cell (iPSC) line (JUCTCi018-A) from a patient with Charcot-Marie-Tooth disease type 2EE (CMT2EE) due to a homozygous c.122G > A p.(Arg41Gln) mutation in the MPV17 gene.
A Ababneh N et al.·Stem Cell Res
2024
MPV17 Prevents Myocardial Ferroptosis and Ischemic Cardiac Injury through Maintaining SLC25A10-Mediated Mitochondrial Glutathione Import.
Xu T et al.·Int J Mol Sci
2024🔓 Open Access
Liver transplantation for mitochondrial DNA depletion syndrome caused by MPV17 deficiency: a case report and literature review.
Wei LY et al.·Front Surg
2024🔓 Open AccessReview
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Focal Segmental GlomerulosclerosisNephrotic SyndromeEnd Stage Renal Disease

Genetic Causes of FSGS, Nephrotic Syndrome, or Kidney Failure

ACTIVE NOT RECRUITING
NCT02194582Beth Israel Deaconess Medical CenterStarted 1996-06
Transplant ComplicationKidney TransplantLiver Transplant

"A Privacy-protecting Environment for Child Transplants Health Related and Genomic Data Integration in the European Reference Network"

NOT YET RECRUITING
NCT07194057Instituto de Investigación Hospital Universitario La PazStarted 2025-09-30
Whole genome sequencingPolygenic Risk Score CalculationMethylome and episignatures
Nephrotic SyndromeFocal Segmental GlomerulosclerosisAPOL1 Associated Kidney Disease

Predictive Determinants of Nephrotic Syndrome Remission in Patients With At-risk Polymorphism of APOL1

NOT YET RECRUITING
NCT06443034Assistance Publique - Hôpitaux de ParisStarted 2024-06-30
Focal Segmental Glomerulosclerosis

A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)

RECRUITING
NCT07220083Phase PHASE3Boehringer IngelheimStarted 2026-02-16
BI 764198Placebo
ANCA Associated VasculitisExtramembranous GlomerulopathyNephrotic Syndrome, Minimal Change

Epithelial Dysmetabolism and Renal Fibrosis in ANCA Vasculitis

NOT YET RECRUITING
NCT07010250Assistance Publique - Hôpitaux de ParisStarted 2025-06-02
Nephrotic Syndrome

INSIGHT (Insight Into Nephrotic Syndrome)

RECRUITING
NCT01605266The Hospital for Sick ChildrenStarted 2011-01
Adenine Phosphoribosyltransferase DeficiencyAH AmyloidosisAHL Amyloidosis

National Registry of Rare Kidney Diseases

RECRUITING
NCT06065852UK Kidney AssociationStarted 2009-11-06
Mitochondrial DiseasesMitochondrial EncephalomyopathyMitochondrial Encephalopathy

Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome

RECRUITING
NCT04802707Phase PHASE2Kenneth Myers, MDStarted 2021-10-18
deoxycytidine and deoxythymidine
HIV NephropathyKidney InjuryKidney Diseases

Genetic Determinants of Kidney Disease in People of African Ancestry With HIV

ACTIVE NOT RECRUITING
NCT05685810King's College Hospital NHS TrustStarted 2018-05-01

External Resources

Links to major genomics databases and tools