Non-Structural Nuclear Genes in Mitochondrial Disease

Last update: March 2012

Complex Assembly

Complex Name OMIM Function Chromosome Inheritance Clinical Phenotype References
I NDUFAF1(CIA30) 606934 Assembly 15q13.3 AR Cardioencephalomyopathy (26)
I NDUFAF2(B17.2L) 609653 Assembly 5q12.1 AR Early onset progressive encephalopathy (45)
I NDUFAF3 612911 Assembly 3p21.31 AR Neonatal encephalopathy (13)
I NDUFAF4(HRPAP20) 611776 Assembly 6q16.1 AR Infantile encephalopathy (23)
I C20orf7 612360 Assembly 20p12.1 AR LS (6,24)
I NUBPL 613621 Assembly 14q12 AR Encephalomyopathy (5)
I FOXRED1 613622 Unknown 11q24.2 AR LS (5)
I ACAD9 611103 Assembly and activity 3q26 AR Hypertrophic cardiopathy encephalopathy (7)
II SDHAF1 612848 Assembly 19q12-q13.2 AR Leukoencephalopathy (10)
II SDHAF2 613019 Assembly 11q12.2 AD Autosomal dominant paraganglioma type 2 (12)
III BCS1L 603647 Assembly 2q33 AR Encephalopathy, hepatic failure and tubulopathy, LS, GRACILE syndrome, Bjornstad Syndrome (28,59,60)
IV SURF1 185620 Assembly 9q34 AR LS (75,76)
IV SCO1 603644 Copper transport 17p13-p12 AR Neonatal hepatic failure and encephalopathy (70)
IV SCO2 604272 Copper transport 22q13 AR Neonatal Cardioencephalomyopathy (73)
IV COX10 602125 Heme A farnesyltransferase 17p12-p11.2 AR Neonatal tubulopathy and encephalopathy, LS, cardiomyopathy (55,70)
IV COX15 603646 Heme A synthesis 10q24 AR Early-onset hypertrophic cardiomyopathy, LS (52,56)
IV LRPPRC 220111 Assembly 2p21-p16 AR French-Canadian LS (57)
IV FASTKD2 612322 Role in apoptosis 2q33.3 AR Encephalomyopathy (19)
IV TACO1 612958 Translational activator of COX1 17q22-q24.2 AR LS (16)
V ATPAF2 608918 Assembly 17p11.2 AR Early-onset encephalopathy, Lactic acidosis (49)
V TMEM70 604273 Assembly 8q21.11 AR Neonatal encephalopathy, cardiomyopathy (18)

MtDNA Stability

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
POLG (PEOA1) 174763 Polymerase gamma mtDNA replication 15q25 AD-AR Alpers syndrome, AD-PEO and AR-PEO, male infertility, SANDO* syndrome, SCAE* (51,63,66)
POLG2 (PEOA4) 610131 catalytic subunit of DNA polymerase gamma 17q23-q24 AD AD-PEO (36)
ANT1 (PEOA2) 609283 ADenine nucleotide translocator isoform 1 4q35 AD AD-PEO, multiple mtDNA deletions (69)
MPV17 137960 regulation of mtDNA copy number 2p23-p21 AR Hepatocerebral MDDS (40)
C10ORF2 (PEOA3) 609286 Twinkle helicase 10q24 AD AD-PEO, SANDO syndrome (43,65)
TYMP (ECGF1) 603041 Thymidine phosphorylase 22q13.32-qter AR MNGIE, mtDNA depletion (72)
DGUOK 601465 Deoxyguanosine kinase Mitochondrial dNTP pool maintenance 2p13 AR Hepatocerebral mtDNA depletion syndrome (61)
RRM2B (PEOA5) 604712 ribonucleotide reductase M2 B dNTP pool 8q23.1 AR Encephalomyopathic Renal tubulopathy MNGIE, AD-PEO (14,15,25)
SUCLA2 603921 succinate-CoA ligase, ADP-forming, beta subunit 13q12.2-q13 AR Encephalomyopathy with methylmalonic aciduria (42)
SUCLG1 611224 succinate-CoA ligase, alpha subunit 2p11.2 AR Encephalomyopathy with methylmalonic aciduria (30)
TK2 188250 Thymidine kinase Mitochondrial dNTP pool maintenance 16q22 AR Myopathic mtDNA depletion (64)

Mitochondrial Import

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
DDP 304700 Protein import Xq22 X-linked Deafness-dystonia or Mohr-Tranebjaerg syndrome (81)
DNAJC19 608977 Protein import 3q26.3 AR Cardiomyopathy, ataxia (35)

Mitochondrial Protein Synthesis

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
EFG1 609060 Elongation factor G1; mitochondrial translation defect 3q25 AR Severe hepatoencephalopathy and lactic acidosis (48)
YARS2 610957 tyrosyl-tRNA synthetase 12p11.21 AR myopathy, lactic acidosis, and sideroblastic anemia-2 (8)
SARS2 612804 seryl-tRNA synthetase 19q13.2 AR Hyperuricemia, pulmonary hypertension, renal failure (3)
DARS2 611105 aspartyl-tRNA synthetase 1q25.1 AR Leukoencephalopathy and lactic acidosis (32)
RARS2 611523 ARginyl-tRNA synthetase 6q16.1 AR Pontocerebellar hypoplasia (27)
MRPS16 609204 Mitochondrial translation 10q22.1 AR neonatal lactic acidosis corpus callosum agenesis (50)
MRPS22 605810 Mitochondrial translation 3q23 AR cardiomyopathy, tubulopathy (31)
TSFM 604723 Mitochondrial translation elongation 12q13-q14 AR Encephalomyopathy, hypertrophic cardiomyopathy (39)
TUFM 602389 Mitochondrial translation elongation 16p11.2 AR leukodystrophy with micropolygyria (33)

Iron Homeostasis

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
FRDA 606829 Frataxin Trinuc. repeat 9q13 AR Friedreich ataxia, neuropathy, cardiomyopathy, diabetes (78,80)
ABCB7 301310 Iron transport Xq13.1-q13.3 X-linked X-linked sideroblastic anemia with ataxia (71)
GLRX5 205950 Iron-sulfur cluster biosynthesis 3p22.1 AR Sideroblastic anemia (11)
ISCU 255125 Iron-sulfur cluster biosynthesis 12q23.3 AR Myopathy, lactic acidosis, exercise intolerance (21)
BOLA3 613183 Iron-sulfur cluster biosynthesis 2p13.1 AR encephalomyopathy, cardiomyopathy (4)
NFU1 608100 Iron-sulfur cluster biosynthesis 2p13.3 AR lactic acidosismultiple respiratory chain deficiency (4)

Coenzyme Q10 biogenesis

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
COQ2 609825 CoQ10 deficiency 4q21-q22 AR Encephalomyopathy, nephropathy (38)
COQ4 612898 CoQ10 deficiency 9q34.13 AR Encephalomyopathy, mental retardation (2)
COQ9 612837 CoQ10 deficiency 16q13 AR Neonatal lactic acidosis Seizures, cardiomyopathy (9)
APTX 606350 CoQ10 deficiency 9p13.3 AR Cerebellar ataxia oculomotor apraxia (46)
PDSS1 607429 CoQ10 deficiency 10p12.1 AR Deafness, valvulopathy, mental retardation (29)
PDSS2 610564 CoQ10 deficiency 6q21 AR LS, nephrotic syndrome (37)
CABC1 606980 CoQ10 deficiency 1q42.2 AR Cerebellar ataxia, lactic acidosis (22)

Chaperone Function

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
SPG7 607259 Paraplegin ATPase protease 16q24.3 AR Spastic paraplegia (74)
HSPD1 118190 Mitochondrial chaperone 2q33.1 AR Spastic paraplegia, leukodystrophy (20)

Mitochondrial Integrity

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
OPA1 165500 Dynamin-related protein 3q28-q29 AD AD-Optic Atrophy
Multiple deletions
MFN2 609260 Mitofusin Mitochondrial fusion 1p36-p35 AD Charcot-Marie-Tooth Disease-2A2 (CMT2A2)
Multiple deletions
DLP1 603850 Mitochondrial and peroxisomal fission 12p11.21 AD Microcephaly, abnormal brain development, optic atrophy, lactic acidosis (34)
G4.5 (Tafazzin) 302060 Cardiolipin defect Xq28 X-linked Barth syndrome, X-linked dilated cardiomyopathy (77,79)
RMRP 250250 RNAse Mitochondrial RNA Processing 9p13-p12 AR Metaphyseal chondrodysplasia or Cartilage-hair hypoplasia (58,62)

Mitochondrial Metabolism

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
PDHA1 308930 Pyruvate dehydrogenase E1-α subunit Xp22.2-p22.1 X-linked LS (82)
ETHE1 602473 Ethylmalonic acid metabolism 19q13 AR Encephalopathy, ethylmalonic aciduria (41,53)
PUS1 600462 pseudouridine synthase 12q24.33 AR myopathy, lactic acidosis, and sideroblastic anemia (47)

Abbreviations LS: Leigh Syndrome; SANDO: Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoparesis; SCAE: Spinocerebellar Ataxia with Epilepsy; GRACILE syndrome: Growth Retardation, Amino aciduria, Cholestasis, Iron overload, Lactic acidosis, and Early death; MNGIE: Mitochondrial NeuroGastroIntestinal Encephalopathy; MDDS: Mitochondrial DNA Depletion Syndrome


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76. Zhu, Z., Yao, J., Johns, T., Fu, K., De Bie, I., Macmillan, C., Cuthbert, A. P., Newbold, R. F., Wang, J., Chevrette, M., Brown, G. K., Brown, R. M. and Shoubridge, E. A. (1998). "SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome". Nature Genetics 20(4):337-343.

77. D'Adamo, P., Fassone, L., Gedeon, A., Janssen, E. A., Bione, S., Bolhuis, P. A., Barth, P. G., Wilson, M., Haan, E., Orstavik, K. H., Patton, M. A., Green, A. J., Zammarchi, E., Donati, M. A. and Toniolo, D. (1997). "The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies". American Journal of Human Genetics 61(4):862-867.

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The original version of this table was posted in 2006, reproduced with permission from PRINCIPLES AND PRACTICE OF MEDICAL GENETICS, 5/e. © 2006 Elsevier Ltd.

Topic revision: r1 - 17 Nov 2015, UnknownUser
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