. 2015 Aug 5;16(8):18054–18076. doi: 10.3390/ijms160818054

Table 1.

Genes involved in disorders featuring mitochondrial DNA instability.

Pathway	Gene	Locus	Encoded Protein	Transmission	Onset	mtDNA Defects	Tissues Mainly Affected	Clinical Phenotypes
mtDNA replication	POLG	15q25	DNA polymerase gamma, catalytic subunit	AD, AR	Adult	dels	muscle	PEO, MM
				AR	Infantile	depl	liver	MDS, ME, AS
				AR	Adult	depl	cerebellum	MIRAS
	POLG2	17q	DNA polymerase gamma, accessory subunit	AD	Adult	dels	muscle	PEO
	PEO1	10q24	Twinkle	AD	Adult	dels	muscle	PEO
				AR	Infantile	depl	liver	MDS
				AR	Infantile	depl	brain	IOSCA, ME
mtDNA repair	DNA2	10q21.3–q22.1	DNA replication helicase/nuclease 2	AD	Adult	dels	muscle	PEO, MM
mtDNA repair	MGME1	20p11.23	Mitochondrial genome maintenance exonuclease 1	AR	Adult	dels/depl	muscle	PEO, MM
dNTPs pools maintenance	SLC25A4	4q35	Adenine nucleotide translocator	AD	Adult	dels	muscle	PEO
	TYMP	22q13	Thymidine phosphorylase	AR	Late childhood Adolescence	dels/depl	muscle	MNGIE
	TK2	16q22–q23.1	Thymidine kinase 2	AR	Early childhood	depl	muscle	MDS
	TK2	16q22–q23.1	Thymidine kinase 2	AR	Adult	dels	muscle	PEO, MM
	DGUOK	2p13	Deoxyguanosine kinase	AR	Neonatal Infantile	depl	liver/muscle	MDS
	DGUOK	2p13	Deoxyguanosine kinase	AR	Adult	dels	muscle	PEO
	RRM2B	8q23.1	Ribonucleotide reductase M2 B	AR	Infantile	depl	muscle	MDS
				AR	Adult	depl	muscle	MNGIE
				AD	Adult	dels	muscle	PEO
	SUCLA2	13q12.2–q13.1	Succinyl-CoA ligase, beta subunit	AR	Early childhood	depl	muscle	MDS
	SUCLG1	2p11.2	Succinyl-CoA ligase, alpha subunit	AR	Neonatal Infantile	depl	muscle/liver	MDS
	ABAT	16p13.2	4-aminobutyrate aminotransferase	AR	Infantile	depl	brain/muscle	MDS
Mitochondrial dynamics	OPA1	3q28–q29	Mitochondrial dynamin-like GTPase	AD	Adult	dels	muscle	OA plus
	MFN2	1p36.22	Mitofusin 2	AR	Adult	dels	muscle	OA plus
	MPV17	2p23.2	Mpv17 mitochondrial inner membrane protein	AR	Neonatal Infantile	depl	liver	MDS
	MPV17	2p23.2	Mpv17 mitochondrial inner membrane protein	AR	Adult	dels	brain	ME
	FBXL4	6q16.1	F-box and leucine-rich repeat (LRR) protein	AR	Neonatal Infantile	depl	brain/muscle	ME/

Abbreviations: mitochondrial DNA (mtDNA), autosomal dominant (AD), autosomal recessive (AR), multiple mtDNA deletions (dels), mtDNA depletion (depl), progressive external ophthalmoplegia (PEO), mitochondrial myopathy (MM), mtDNA depletion syndrome (MDS), Alpers’ syndrome (AS), mitochondrial recessive ataxia syndrome (MIRAS), mitochondrial encephalopathy (ME), optic atrophy (OA), mitochondrial neurogastrointestinal encephalopathy (MNGIE), infantile-onset spinocerebellar ataxia (IOSCA).