MPV17

Chr 2AR

mitochondrial inner membrane protein MPV17

Also known as: CMT2EE, MTDPS6, SYM1

This protein localizes to the mitochondrial inner membrane and functions in reactive oxygen species metabolism. Mutations cause mitochondrial DNA depletion syndrome 6 (hepatocerebral type) and Charcot-Marie-Tooth disease type 2EE through an autosomal recessive inheritance pattern. The pathogenic mechanism involves gain-of-function effects that disrupt normal mitochondrial function.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.792 OMIM phenotypes
Clinical SummaryMPV17
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
9 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.79LOEUF
pLI 0.000
Z-score -0.65
OE 1.20 (0.791.79)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.24Z-score
OE missense 0.93 (0.781.11)
89 obs / 95.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.20 (0.791.79)
00.351.4
Missense OE0.93 (0.781.11)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 14 / 11.6Missense obs/exp: 89 / 95.5Syn Z: 0.26
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMPV17-related mitochondrial DNA depletion syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7228th %ile
GOF
0.7126th %ile
LOF
0.3550th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
Mitochondrial DiseasesMitochondrial EncephalomyopathyMitochondrial Encephalopathy

Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome

RECRUITING
NCT04802707Phase PHASE2Kenneth Myers, MDStarted 2021-10-18
deoxycytidine and deoxythymidine
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
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
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
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
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
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
Clinical Literature
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