MPV17

mitochondrial inner membrane protein MPV17

Basic information

Region (hg38): 2:27309492-27325680

Links

ENSG00000115204 ∙ NCBI:4358 ∙ OMIM:137960 ∙ HGNC:7224 ∙ Uniprot:P39210 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial DNA depletion syndrome 6 (hepatocerebral type) (Strong), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR
• Charcot-Marie-Tooth disease, axonal, type 2EE (Strong), mode of inheritance: AR
• mitochondrial DNA depletion syndrome 6 (hepatocerebral type) (Strong), mode of inheritance: AR
• mitochondrial DNA depletion syndrome 6 (hepatocerebral type) (Supportive), mode of inheritance: AR
• mitochondrial DNA depletion syndrome 6 (hepatocerebral type) (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)	AR	Biochemical; Gastrointestinal; Oncologic	Glycemic control (eg, with cornstarch) has been shown to slow the progression of hepatic disease; Liver transplanation has been described, though the efficacy is unclear; Awareness of the possible risk of hepatocellular carcinoma may be beneficial	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic	16909392; 16582910; 18695062; 19520594; 19012992; 20074988; 21511859; 22508010; 22593919; 26437932; 30298599

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MPV17 gene.

• not_provided (271 variants)
• Mitochondrial_DNA_depletion_syndrome_6_(hepatocerebral_type) (81 variants)
• Charcot-Marie-Tooth_disease,_axonal,_type_2EE (60 variants)
• MPV17-related_disorder (20 variants)
• Inborn_genetic_diseases (17 variants)
• Mitochondrial_DNA_depletion_syndrome,_hepatocerebral_form (16 variants)
• Mitochondrial_DNA_depletion_syndrome_15_(hepatocerebral_type) (14 variants)
• Mitochondrial_DNA_depletion_syndrome (13 variants)
• not_specified (10 variants)
• MPV17-related_mitochondrial_DNA_maintenance_defect (2 variants)
• Mitochondrial_DNA_maintenance_disorder (1 variants)
• Mitochondrial_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MPV17 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002437.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	1	2	75	1	80
missense	4	19	65	5		93
nonsense	7	14	1			22
start loss		1				1
frameshift	16	11				27
splice donor/acceptor (+/-2bp)	4	19	2			25
Total	32	65	70	80	1

Highest pathogenic variant AF is 0.00009603958

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MPV17	protein_coding	protein_coding	ENST00000380044	7	16188

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.237	89	95.5	0.932	0.00000537	1110
Missense in Polyphen		17	25.218	0.67413		316
Synonymous	0.262	36	38.1	0.946	0.00000195	363
Loss of Function	-0.646	14	11.6	1.20	5.13e-7	132

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00111	0.00110
Ashkenazi Jewish	0.000302	0.000298
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000167	0.000167
Middle Eastern	0.00	0.00
South Asian	0.000163	0.000163
Other	0.000331	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in mitochondria homeostasis. May be involved in the metabolism of reactive oxygen species and control of oxidative phosphorylation and mitochondrial DNA (mtDNA) maintenance.
• Pathway: Peroxisome - Homo sapiens (human);Metabolism of proteins;Peroxisomal protein import (Consensus)

Intolerance Scores

• loftool: 0.402
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.261

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Zebrafish Information Network

• Gene name: mpv17
• Affected structure: iridophore
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: mitochondrial genome maintenance;protein targeting to peroxisome;glomerular basement membrane development;cellular response to reactive oxygen species;homeostatic process;inner ear development;regulation of reactive oxygen species metabolic process
• Cellular component: cytoplasm;mitochondrion;mitochondrial inner membrane;peroxisome;peroxisomal membrane;cytosol;integral component of membrane
• Molecular function: molecular_function