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…

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, axonal, type 2EEMIM #618400

Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)MIM #256810

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · AR · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.79

LOEUF

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in MPV17?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

413 rare PASS variants

Rare truncating (LoF)

1 in 770

102 rare PASS variants

Rare synonymous (reference)

1 in 360

93 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MPV17. 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 270	1 in 2,200
South Asian	~43k	1 in 150	1 in 550
Remaining (unassigned)	~30k	1 in 110	1 in 370
European (Finnish)	~27k	1 in 430	≈ 1 in 27,000
Admixed American	~22k	1 in 120	1 in 560
African / African American	~21k	1 in 120	1 in 400
East Asian	~20k	1 in 120	1 in 570
Ashkenazi Jewish	~13k	1 in 430	1 in 1,300
Middle Eastern	~2,884	1 in 120	≈ 1 in 930

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): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓