MPV17

Chr 2AR

mitochondrial inner membrane protein MPV17

Also known as: CMT2EE, MTDPS6, SYM1

NCBI Gene: 4358 ENSG00000115204 UniProt: P39210 OMIM: 137960

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.792 OMIM phenotypes

Clinical Summary— MPV17

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

98 unique Pathogenic / Likely Pathogenic· 93 VUS of 385 total submissions

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Clinical Trials

8 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MPV17

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.24Z-score

OE missense 0.93 (0.78–1.11)

89 obs / 95.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.20 (0.79–1.79)

0≤0.351.4

Missense OE?0.93 (0.78–1.11)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

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

This gene — mechanism propensity

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

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

385 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36

Likely Pathogenic62

VUS93

Likely Benign157

Benign5

Conflicting24

Pathogenic

Likely Pathogenic

VUS

157

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	25	3	8	0	36
Likely Pathogenic	47	12	2	1	62
VUS	1	65	26	1	93
Likely Benign	0	1	86	70	157
Benign	0	0	3	2	5
Conflicting	—				24
Total	73	81	125	74	377

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap MPV17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →