Table 2.
Heterozygous mutations in genes involved in metabolisms
| Chromosome | Position | Wt seq. | MT seq | Quality | Mutation | Gene | Product | DNA changes | Protein changes | Read number | MT seq. Ratio | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| WT seq. | MT seq. | |||||||||||
| Glycolysis/Gluconeogenesis | ||||||||||||
| III | 456,890 | C | T | 327.19 | missense | AGOS_ACR056W | Phosphoglycerate mutase (AgGPM1) | c.374C > T | p.A125V | 28 | 12 | 0.300 |
| IV | 287,997 | T | C | 503.19 | missense | AGOS_ADL237C | 6-phosphofructo-2-kinase (AgPFK26) | c.1796A > G | p.D599G | 24 | 18 | 0.429 |
| IV | 1,362,124 | A | T | 725.19 | missense | AGOS_ADR368W | Pyruvate kinase (AgPYK1) | c.1040A > T | p.K347M | 21 | 23 | 0.523 |
| V | 242,262 | A | C | 708.19 | missense | AGOS_AEL208W | Alpha subunit of phosphofructokinase (AgPFK1) | c.2255A > C | p.K752T | 27 | 23 | 0.460 |
| V | 426,255 | C | T | 700.19 | missense | AGOS_AEL106W | Fructose-2,6-bisphosphatase (AgFBP26) | c.103C > T | p.R35W | 21 | 23 | 0.523 |
| VI | 96,950 | A | C | 1088.19 | missense | AGOS_AFL185W | Beta subunit of phosphofructokinase (AgPFK2) | c.1963A > C | p.N655H | 35 | 37 | 0.514 |
| VI | 97,509 | AT | A | 907.15 | frameshift | AGOS_AFL185W | Beta subunit of phosphofructokinase (AgPFK2) | c.2526Tdel | p.Phe842fs | 20 | 32 | 0.615 |
| TCA cycle | ||||||||||||
| I | 346,384 | G | A | 758.19 | missense | AGOS_AAR004C | Citrate synthase (AgCIT1) | c.68C > T | p.T23M | 18 | 25 | 0.581 |
| I | 634,291 | G | T | 991.19 | Nonsense | AGOS_AAR162C | Pyruvate carboxylase (AgPYC2) | c.3266c > A | p.S1089* | 31 | 33 | 0.514 |
| I | 634,669 | A | T | 836.19 | missense | AGOS_AAR162C | Pyruvate carboxylase (AgPYC2) | c.2888 T > A | p.L963Q | 21 | 26 | 0.553 |
| III | 238,489 | T | G | 729.19 | missense | AGOS_ACL065C | Iron-sulfur protein subunit of succinate dehydrogenase (AgSDH2) | c.697A > C | p.T233P | 25 | 23 | 0.479 |
| III | 238,962 | G | A | 1051.19 | missense | AGOS_ACL065C | Iron-sulfur protein subunit of succinate dehydrogenase (AgSDH2) | c.224C > T | p.T75M | 20 | 32 | 0.615 |
| III | 451,903 | G | A | 879.19 | missense | AGOS_ACR052W | Flavoprotein subunit of succinate dehydrogenase (AgSDH1)a | c.1132G > A | p.D378N | 17 | 27 | 0.614 |
| IV | 403,968 | C | T | 488.19 | missense | AGOS_ADL164C | Malate dehydrogenase (AgMDH2) | c.196G > A | p.A66T | 27 | 16 | 0.372 |
| IV | 644,214 | A | G | 568.19 | missense | AGOS_ADL032W | Aconitase (AgACO1) | c.1367A > G | p.D456G | 10 | 16 | 0.615 |
| V | 1,328,889 | C | A | 922.19 | missense | AGOS_AER374C | Subunit of the mitochondrial alpha-ketoglutarate dehydrogenase (AgKGD1) | c.1837G > T | p.D613Y | 27 | 27 | 0.5 |
| V | 1,328,948 | G | A | 711.19 | missense | AGOS_AER374C | Subunit of the mitochondrial alpha-ketoglutarate dehydrogenase (AgKGD1) | c.1778C > T | p.T593M | 25 | 23 | 0.479 |
| VI | 810,404 | G | T | 482.19 | missense | AGOS_AFR207C | Subunit of succinate dehydrogenase (AgSDH3) | c.200C > A | p.S67Y | 20 | 18 | 0.473 |
| VI | 1,103,105 | G | A | 636.19 | missense | AGOS_AFR367W | Fumarate reductase (AgOSM1) | c.622G > A | p.A208T | 21 | 19 | 0.475 |
| VI | 1,585,840 | G | T | 635.19 | missense | AGOS_AFR629W | Aconitase (AgACO2) | c.1894G > T | p.D632Y | 36 | 24 | 0.400 |
| VII | 1,652,466 | A | G | 970.19 | missense | AGOS_AGR323C | E3-binding protein of pyruvate dehydrogenase (AgPDX1) a | c.677 T > C | p.L226P | 16 | 28 | 0.636 |
| VI | 681,082 | C | T | 624.19 | missense | AGOS_AFR134C | Alpha subunit of succinyl-CoA ligase (AgLSC1) | c.193G > A | p.A65T | 23 | 24 | 0.510 |
| Mitochondria | ||||||||||||
| II | 324,797 | A | G | 633.19 | missense | AGOS_ABL038W | Mitochondrial aspartate aminotransferase (AgAAT1) | c.224A > G | p.D75G | 20 | 19 | 0.487 |
| II | 325,256 | C | T | 487.19 | missense | AGOS_ABL038W | Mitochondrial aspartate aminotransferase (AgAAT1) | c.683C > T | p.T228M | 25 | 18 | 0.419 |
| IV | 532,772 | C | A | 1079.19 | missense | AGOS_ADL087W | Cytochrome b reductase (AgCBR1)a | c.155C > A | p.T52N | 25 | 34 | 0.576 |
| IV | 1,458,400 | G | T | 559.19 | missense | AGOS_ADR417W | Mitochondrial aldehyde dehydrogenase (AgALD4) | c.561G > T | p.W187C | 21 | 17 | 0.447 |
| V | 1,227,029 | G | A | 503.19 | missense | AGOS_AER321W | Mitochondrial D-lactate dehydrogenase (AgDLD1) a | c.190G > A | p.A64T | 11 | 15 | 0.577 |
| VI | 899,775 | G | A | 668.19 | missense | AGOS_AFR255W | Mitochondrial tRNA translation optimization 1 (MTO1) a | c.1423G > A | p.G475S | 27 | 22 | 0.449 |
| VI | 1,243,899 | C | T | 819.19 | missense | AGOS_AFR447C | NADH:ubiquinone oxidoreductase (AgNDI1) a | c.943G > A | p.V315M | 16 | 26 | 0.619 |
| VII | 1,441,269 | C | A | 874.19 | missense | AGOS_AGR196W | Glutathione-disulfide reductase (AgGLR1) a | c.1415C > A | p.S472Y | 27 | 28 | 0.509 |
| Riboflavin metabolism | ||||||||||||
| II | 194,781 | G | T | 733.19 | missense | AGOS_ABL109W | Riboflavin kinase (AgFMN1) | c.80G > T | p.S27I | 20 | 22 | 0.524 |
| IV | 182,017 | G | A | 687.19 | missense | AGOS_ADL296C | GTP cyclohydrolase II (AgRIB1) | c.230C > T | p.P77L | 23 | 23 | 0.500 |
| Glycine, serine, threonine metabolism | ||||||||||||
| I | 448,391 | G | A | 962.19 | missense | AGOS_AAR059C | Threonine synthase (AgTHR4) | c.685C > T | p.R229W | 19 | 29 | 0.604 |
| III | 125,457 | G | A | 821.19 | missense | AGOS_ACL130C | Phosphoserine phosphatase (AgSER2) | c.140C > T | p.A47V | 28 | 27 | 0.491 |
| III | 727,688 | C | T | 572.19 | missense | AGOS_ACR215C | Serine hydroxymethyltransferase (AgSHM2) | c.593G > A | p.R198Q | 24 | 20 | 0.455 |
| VII | 1,057,290 | T | C | 592.19 | missense | AGOS_AGR012C | Cystathionine beta-synthase (AgCYS4) | c.269A > G | p.K90R | 16 | 19 | 0.543 |
| VII | 1,446,998 | A | G | 720.19 | missense | AGOS_AGR200W | Threonine aldolase (AgGLY1) | c.1088A > G | p.Y363C | 14 | 20 | 0.588 |
| Branched-chain amino acid metabolism | ||||||||||||
| I | 305,862 | G | A | 960.19 | missense | AGOS_AAL021W | Small subunit of acetohydroxyacid synthase (AgILV6) | c.140G > A | p.S47N | 25 | 29 | 0.537 |
| I | 305,877 | G | A | 923.19 | missense | AGOS_AAL021W | Small subunit of acetohydroxyacid synthase (AgILV6) | c.155G > A | p.S52N | 28 | 30 | 0.517 |
| I | 306,395 | G | T | 711.19 | missense | AGOS_AAL021W | Small subunit of acetohydroxyacid synthase (AgILV6) | c.673G > T | p.G225C | 23 | 22 | 0.489 |
| II | 729,493 | G | A | 1028.19 | missense | AGOS_ABR174W | Branched-chain amino acid biosynthesis activator (AgLEU3) | c.704G > A | p.G235D | 23 | 33 | 0.589 |
| II | 730,278 | G | A | 915.19 | missense | AGOS_ABR174W | Branched-chain amino acid biosynthesis activator (AgLEU3) | c.1489G > A | p.A497T | 22 | 26 | 0.542 |
| VI | 12,855 | C | A | 543.19 | missense | AGOS_AFL229W | 2-isopropylmalate synthase (AgLEU4) | c.1051C > A | p.P351T | 26 | 19 | 0.422 |
| VII | 1,381,676 | C | T | 564.19 | missense | AGOS_AGR169W | 3-isopropylmalate dehydratase (LEU1) | c.226C > T | p.H76Y | 12 | 17 | 0.586 |
| VII | 1,382,933 | T | C | 745.19 | missense | AGOS_AGR169W | 3-isopropylmalate dehydratase (LEU1) | c.1483 T > C | p.S495P | 26 | 25 | 0.490 |
| Aromatic amino acid metabolism | ||||||||||||
| II | 206,627 | C | T | 580.19 | missense | AGOS_ABL102C | 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase (AgARO3) | c.935G > A | p.C312Y | 28 | 18 | 0.391 |
| II | 799,743 | C | A | 554.19 | missense | AGOS_ABR209W | Anthranilate synthase (AgTRP2) | c.982C > A | p.L328I | 15 | 16 | 0.516 |
| VI | 1,313,765 | T | A | 750.19 | missense | AGOS_AFR485C | Tryptophan synthase (AgTRP5) | c.1917A > T | p.Q639H | 33 | 29 | 0.468 |
| VI | 1,426,745 | G | T | 476.19 | missense | AGOS_AFR548C | Aromatic aminotransferase I (AgARO8) | c.544C > A | p.P182T | 29 | 16 | 0.356 |
| VII | 1,157,861 | G | A | 690.19 | missense | AGOS_AGR066W | Pentafunctional aromatic polypeptide (AgARO1) | c.3536G > A | p.R1179H | 22 | 21 | 0.488 |
| VII | 1,158,247 | G | A | 921.19 | missense | AGOS_AGR066W | Pentafunctional aromatic polypeptide (AgARO1) | c.3922G > A | p.G1308S | 29 | 31 | 0.517 |
| Sulfur amino acid metabolism | ||||||||||||
| I | 361,523 | G | A | 834.19 | missense | AGOS_AAR010W | Transcriptional activator of sulfur metabolism (AgMET28) | c.719G > A | p.R240Q | 28 | 25 | 0.472 |
| II | 259,309 | C | T | 578.19 | missense | AGOS_ABL077W | Beta subunit of sulfite reductase (AgMET5) a | c.3002C > T | p.A1001V | 25 | 19 | 0.432 |
| II | 804,448 | C | T | 685.19 | missense | AGOS_ABR212C | Cobalamin-independent methionine synthase (AgMET6) | c.499G > A | p.G167S | 25 | 23 | 0.479 |
| III | 259,886 | C | A | 1053.19 | missense | AGOS_ACL059C | Peroxisomal cystathionine beta-lyase (AgSTR3) | c.1210G > T | p.V404L | 16 | 32 | 0.667 |
| III | 585,577 | C | A | 547.19 | missense | AGOS_ACR134W | Folylpolyglutamate synthetase (AgMET7) | c.1135C > A | p.L379M | 25 | 17 | 0.405 |
| IV | 646,485 | G | A | 838.19 | missense | AGOS_ADL031W | O-acetyl homoserine-O-acetyl serine sulfhydrylase (AgMET17) | c.302G > A | p.G101D | 23 | 26 | 0.531 |
| V | 1,338,633 | G | A | 974.19 | missense | AGOS_AER377C | Component of cytosolic iron-sulfur protein assembly machinery (AgMET18) | c.1061C > T | p.T354I | 28 | 31 | 0.525 |
| VI | 1,699,984 | C | A | 936.19 | missense | AGOS_AFR682C | L-homoserine-O-acetyltransferase (AgMET2) | c.1045G > T | p.A349S | 20 | 32 | 0.615 |
| VI | 1,720,007 | C | T | 393.19 | missense | AGOS_AFR692C | S-adenosylmethionine synthetase (AgSAM2) | c.731G > A | p.G244D | 30 | 13 | 0.302 |
| VII | 1,511,391 | C | A | 892.19 | missense | AGOS_AGR237C | Alpha subunit of assimilatory sulfite reductase (AgMET10) | c.2268G > T | p.E756D | 22 | 28 | 0.560 |
| VII | 1,512,792 | C | A | 606.19 | missense | AGOS_AGR237C | Alpha subunit of assimilatory sulfite reductase (AgMET10) | c.867G > T | p.E289D | 27 | 22 | 0.449 |
| VII | 1,685,571 | G | A | 715.19 | missense | AGOS_AGR343W | Component of cytosolic iron-sulfur protein assembly (CIA) machinery | c.563G > A | p.R188H | 24 | 21 | 0.467 |
| Other amino acid metabolism | ||||||||||||
| III | 169,882 | C | T | 367.19 | missense | AGOS_ACL096W | Proline utilization transactivator (AgPUT3) | c.382C > T | p.R128W | 26 | 14 | 0.350 |
| IV | 98,235 | C | A | 727.19 | missense | AGOS_ADL346W | Alpha-aminoadipate reductase (AgLYS2) | c.1648C > A | p.L550M | 27 | 23 | 0.460 |
| VI | 1,397,559 | C | A | 864.19 | missense | AGOS_AFR534W | Small subunit of carbamoyl phosphate synthetase (AgCPA1) | c.976C > A | p.P326T | 29 | 25 | 0.463 |
| VII | 389,521 | C | A | 724.19 | missense | AGOS_AGL165W | Proline oxidase (AgPUT1) a | c.104C > A | p.T35K | 28 | 24 | 0.462 |
| VII | 1,708,538 | T | G | 528.19 | missense | AGOS_AGR357W | Asparaginase (AgASP1) | c.311 T > G | p.I104R | 19 | 17 | 0.472 |
| Purine, pyrimidine nulceotide metabolism | ||||||||||||
| I | 558,677 | G | A | 532.19 | missense | AGOS_AAR120C | Phosphoribosyl-glycinamide transformylase (AgADE8) | c.218C > T | p.T73I | 16 | 16 | 0.500 |
| II | 269,595 | C | A | 593.19 | missense | AGOS_ABL070C | Xanthine-guanine phosphoribosyl transferase (AgXPT1) | c.232G > T | p.D78Y | 29 | 22 | 0.431 |
| II | 784,947 | G | A | 618.19 | missense | AGOS_ABR204C | AMP deaminase (AgAMD1) | c.1553C > T | p.T518I | 38 | 21 | 0.356 |
| III | 132,857 | C | A | 773.19 | missense | AGOS_ACL121C | Trifunctional C1-tetrahydrofolate synthase (AgADE3) | c.2067G > T | p.R689S | 21 | 25 | 0.543 |
| III | 214,069 | A | T | 441.19 | missense | AGOS_ACL077C | Ribose-5-phosphate isomerase (AgRKI1) | c.17 T > A | p.I6N | 29 | 17 | 0.370 |
| III | 636,192 | A | T | 711.19 | missense | AGOS_ACR160C | Nicotinate phosphoribosyltransferase (AgNPT1) | c.84 T > A | p.N28K | 26 | 24 | 0.480 |
| III | 654,234 | C | T | 690.19 | missense | AGOS_ACR170C | Uridylate kinase (AgURA6) | c.152G > A | p.R51H | 14 | 21 | 0.600 |
| III | 715,325 | G | T | 697.19 | missense | AGOS_ACR210C | Phosphoribosylaminoimidazole carboxylase (AgADE2) | C.926C > A | p.A309D | 23 | 21 | 0.477 |
| III | 832,220 | C | T | 957.19 | missense | AGOS_ACR263C | Bifunctional carbamoylphosphate synthetase/aspartate transcarbamylase (AgURA2) | c.2275G > A | p.E759K | 19 | 31 | 0.620 |
| III | 832,428 | C | T | 745.19 | missense | AGOS_ACR263C | Bifunctional carbamoylphosphate synthetase/aspartate transcarbamylase (AgURA2) | c.2067G > A | p.M689I | 27 | 23 | 0.460 |
| IV | 580,072 | G | T | 461.19 | missense | AGOS_ADL057W | Large subunit of ribonucleotide reductase (AgRNR1) | c.2520G > T | p.K840N | 16 | 15 | 0.483 |
| V | 792,520 | T | C | 1069.19 | missense | AGOS_AER083C | 5-phospho-ribosyl-1-pyrophosphate synthetase (AgPRS1) | c.488A > G | p.Q163R | 24 | 33 | 0.578 |
| VI | 896,312 | A | T | 502.19 | missense | AGOS_AFR254C | Aminoimidazole ribotide synthetase and glycinamide ribotide synthetase (AgADE5,7) | c.1654 T > A | p.L552I | 20 | 15 | 0.428 |
| VI | 978,821 | C | A | 584.19 | missense | AGOS_AFR297W | Myb-related transcription factor (AgBAS1) | c.905C > A | p.P302H | 23 | 20 | 0.465 |
| VII | 108,330 | G | A | 674.19 | missense | AGOS_AGL320C | CTP synthase (AgURA7) | c.1361C > T | p.T454I | 23 | 25 | 0.521 |
| VII | 430,379 | G | A | 703.19 | missense | AGOS_AGL146W | GTP cyclohydrolase (AgURC1) | c.1247G > A | p.G416D | 27 | 21 | 0.438 |
| VII | 1,072,826 | T | C | 377.19 | missense | AGOS_AGR022C | Nicotinic acid mononucleotide adenylyltransferase (AgNMA1) | c.814A > G | p.T272A | 26 | 13 | 0.333 |
| Fatty acid metabolism | ||||||||||||
| I | 564,702 | G | A | 769.19 | missense | AGOS_AAR124C | Carnitine acetyl-CoA transferase (AgCAT2) | c.1736C > T | p.S579F | 19 | 23 | 0.548 |
| IV | 1,430,996 | G | A | 829.19 | missense | AGOS_ADR403C | Oleate-activated transcription factor (AgOAF1 or AgPIP2) | c.1405C > T | p.R469C | 22 | 26 | 0.542 |
| IV | 1,436,329 | G | T | 757.19 | missense | AGOS_ADR405C | Oleate-activated transcription factor (AgOAF1 or AgPIP2) | c.2170C > A | p.L724I | 35 | 28 | 0.444 |
| IV | 1,437,793 | G | A | 800.19 | stop_gained | AGOS_ADR405C | Oleate-activated transcription factor (AgOAF1 or AgPIP2) | c.706C > T | p.Q236* | 30 | 25 | 0.455 |
| IV | 1,443,883 | T | A | 729.19 | nonsense | AGOS_ADR408W | Acetyl-coA synthetase (AgACS1) | c.1128 T > A | p.Tyr376* | 21 | 23 | 0.523 |
| V | 794,683 | T | C | 631.19 | missense | AGOS_AER085C | Beta subunit of fatty acid synthetase (AgFAS1) a | c.5837A > G | p.K1946R | 23 | 19 | 0.452 |
| V | 797,843 | T | G | 419.19 | missense | AGOS_AER085C | Beta subunit of fatty acid synthetase (AgFAS1) a | c.2677A > C | p.K893Q | 38 | 15 | 0.283 |
| V | 797,858 | C | A | 1299.19 | missense | AGOS_AER085C | Beta subunit of fatty acid synthetase (AgFAS1) a | c.2662G > T | p.D888Y | 14 | 38 | 0.731 |
| VI | 172,719 | A | T | 746.19 | missense | AGOS_AFL138W | Alpha subunit of fatty acid synthetase (AgFAS2) | c.7A > T | p.M3L | 19 | 26 | 0.578 |
| VI | 175,856 | C | A | 656.19 | missense | AGOS_AFL138W | Alpha subunit of fatty acid synthetase (AgFAS2) | c.3144C > A | p.F1048L | 21 | 21 | 0.500 |
| VI | 1,507,650 | T | A | 742.19 | missense | AGOS_AFR592W | 1-acyl-sn-glycerol-3-phosphate acyltransferase (AgSLC1) | c.832A > T | p.L278M | 21 | 22 | 0.512 |
| VII | 421,657 | G | T | 728.19 | missense | AGOS_AGL148C | Acetyl-coA synthetase (AgACS2) | c.772C > A | p.Q258K | 24 | 24 | 0.500 |
| VII | 422,089 | C | T | 804.19 | missense | AGOS_AGL148C | Acetyl-coA synthetase (AgACS2) | c.340G > A | p.A114T | 25 | 26 | 0.510 |
| VII | 913,244 | C | A | 553.19 | missense | AGOS_AGL060W | 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase (AgFOX2) | c.814C > A | p.P272T | 25 | 17 | 0.405 |
| Heme biosynthesis | ||||||||||||
| I | 380,486 | A | C | 573.19 | missense | AGOS_AAR021W | Protoporphyrinogen oxidase (AgHEM14) a | c.617A > C | p.E206A | 30 | 21 | 0.412 |
| II | 203,080 | T | C | 1002.19 | missense | AGOS_ABL104C | 5-aminolevulinate synthase (AgHEM1) | c.1397A > G | p.E466G | 18 | 31 | 0.633 |
| V | 1,281,270 | T | A | 552.19 | nonsense | AGOS_AER351W | Uroporphyrinogen-III synthase (AgHEM4) | c.762 T > A | p.Y254* | 19 | 20 | 0.513 |
| VII | 1,608,654 | A | AG | 453.15 | frameshift | AGOS_AGR298C | S-adenosyl-L-methionine uroporphyrinogen III transmethylase (AgMET1) | c.1412dupC | p.A472fs | 19 | 19 | 0.500 |
| Other flavoprotein | ||||||||||||
| III | 660,436 | G | T | 853.19 | missense | AGOS_ACR175W | Sulfhydryl oxidase (AgERV2) a | c.441G > T | p.W147C | 28 | 28 | 0.500 |
| IV | 94,090 | G | A | 485.19 | missense | AGOS_ADL348W | Endoplasmic oxidoreductin1 (AgERO1) a | c.386G > A | p.S129N | 20 | 18 | 0.474 |
| Folate metabolism | ||||||||||||
| VII | 1,665,459 | G | A | 658.19 | missense | AGOS_AGR330W | Aminodeoxychorismate lyase (AgABZ2) | c.208G > A | p.V70M | 29 | 23 | 0.442 |
| VII | 1,674,504 | C | A | 813.19 | missense | AGOS_AGR335C | GTP-cyclohydrolase I (AgFOL2) | c.343G > T | p.D115Y | 30 | 25 | 0.455 |
These heterozygous mutations are a subset among all 1382 heterozygous mutations which are shown in Table S2
aFlavoproteins
*Translation stops here