theraseek Panel Gene List by Category

Transcription

1 theraseek Panel Gene List by Category Gene Pathway/Function Association ACAT1 Alpha-methylacetoacetic aciduria Amino acid metabolism Pathway DHTKD1 Charcot-Marie-Tooth disease 2Q, axonal/2-aminoadipic 2-oxoadipic aciduria Amino acid metabolism GAMT Cerebral creatine deficiency syndrome 2 Amino acid metabolism GATM Cerebral creatine deficiency syndrome 3 Amino acid metabolism SLC6A8 Cerebral creatine deficiency syndrome Amino acid metabolism GLRX None identified Antioxidant pathway Pathway GLRX2 None identified Antioxidant pathway Pathway GLRX5 3, pyridoxine-refractory sideroblastic anemia/childhood-onset spasticity with hyperglycinemia Antioxidant pathway Pathway GPX1 Hemolytic anemia Antioxidant pathway Pathway GSTK1 None identified Antioxidant pathway Pathway MSRA None identified Antioxidant pathway Pathway MSRB2 None identified Antioxidant pathway Pathway OXR1 None identified Antioxidant pathway Pathway PARK7 Autosomal recessive early-onset Parkinson disease Antioxidant pathway Pathway PINK1 Early onset Parkinson disease Antioxidant pathway Pathway PNKD Paroxysmal nonkinesigenic dyskinesia Antioxidant pathway PRDX1 None identified Antioxidant pathway Pathway PRDX2 None identified Antioxidant pathway Pathway PRDX3 None identified Antioxidant pathway Pathway PRDX5 None identified Antioxidant pathway Pathway PRDX6 None identified Antioxidant pathway Pathway TRAP1 Functional disease Antioxidant pathway Both ALDH3A2 Sjogren-Larsson syndrome Biopterin pathway Pathway DDAH1 None identified Biopterin pathway Pathway G6PD Favism/hemolytic anemia Biopterin pathway Both NOS3 Susceptibility to late-onset Alzheimer disease, coronary artery spasm, hypertension, ischemic stroke, pregnancyinduced hypertension, placental abruption/vascular functional disease (migraine, POTS, stroke-like episodes) Biopterin pathway Both PAH Phenylketonuria/hyperphenylalaninemia Biopterin pathway Both PTS BH4-deficient hyperphenylalaninemia A Biopterin pathway QDPR BH4-deficient hyperphenylalaninemia C Biopterin pathway SPR DOPA-responsive dystonia Biopterin pathway Both G6PC Glycogen storage disease type 1A Carbohydrate metabolism GK Glycerol kinase deficiency Carbohydrate metabolism Both GPI Nonspherocytic hemolytic anemia Carbohydrate metabolism HK1 Hereditary motor and sensor neuropathyy, Russe type/hemolytic anemia Carbohydrate metabolism HK3 None/PANS Carbohydrate metabolism LDHA Glycogen storage disease XI Carbohydrate metabolism PGAM2 Glycogen storage disease X Carbohydrate metabolism Courtagen Life Sciences Inc. 12 Gill Street Suite 3700 Woburn, MA Fax: MKT /2016

2 Gene Pathway/Function Association PGK1 Phosphoglycerate kinase 1 deficiency Carbohydrate metabolism PKLR Pyruvate kinase deficiency Carbohydrate metabolism SLC16A1 Erythrocyte lactate transporter defect/familial hyperinsulinemic hypoglycemia/monocarboxylate transporter 1 deficiency Carbohydrate metabolism SLC2A1 GLUT1 deficiency syndrome 1 and 2/stomatin-deficient cryohydrocytosis with neurologic defects/dystonia/susceptibility to generalized epilepsy Carbohydrate metabolism SLC22A5 Systemic primary carnitine deficiency Carnitine metabolism Pathway TMLHE Epsilon-trimethyllysine hydroxylase deficiency Carnitine metabolism Both GNAS Pseudohypoparathyroidism (Ia, Ib, Ic)/pseudopseudohypoparathyroidism/progressive osseous heteroplasia Cell signaling pathway TSC1 Tuberous sclerosis/focal cortical dysplasia, Taylor balloon cell type Cell signaling pathway TSC2 Tuberous sclerosis Cell signaling pathway ADCK3 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway APTX Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia Coenzyme q10/nadph pathway Pathway COQ10B None identified Coenzyme q10/nadph pathway Pathway COQ2 Primary Coenzyme Q10 deficiency/susceptibility to multiple system atrophy Coenzyme q10/nadph pathway Pathway COQ3 None identified Coenzyme q10/nadph pathway Pathway COQ4 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway COQ5 None identified Coenzyme q10/nadph pathway Pathway COQ6 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway COQ7 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway COQ9 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway CYBA Chronic granulomatous disease Coenzyme q10/nadph pathway CYBB Chronic granulomatous disease Coenzyme q10/nadph pathway PDSS1 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway PDSS2 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway ATP7A Menkes disease/occipital horn disease/x-linked distal Spinal muscular atrophy Cofactor or metal disorder BTD Biotinidase deficiency Cofactor or metal disorder Pathway GIF Intrinsic factor deficiency Cofactor or metal disorder Both TPK1 Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) Cofactor or metal disorder Pathway VDR Vitamin D-resistant rickets type IIA Cofactor or metal disorder Both ANK2 Cardiac arrhythmia, ankyrin-b-related/long QT syndrome/autism/functional disease candidate Cytoskeleton/extracellular matrix DMD Duchenne muscular dystrophy/becker muscular dystrophy/dilated cardiomyopathy Cytoskeleton/extracellular matrix ELN Cutis laxa/supravalvar aortic stenosis Cytoskeleton/extracellular matrix FLNA Otopalatodigital syndrome types I and II, congenital short bowel syndrome, X-linked cardiac valvular dysplasia, Melnick- Needles, frontometaphyseal dysplasia, periventricular heterotopia, FG syndrome 2 Cytoskeleton/extracellular matrix SPAST Autosomal dominant spastic paraplegia Cytoskeleton/extracellular matrix CYP27A1 Cerebrotendinous xanthomatosis Drug metabolism/detoxification Pathway CYP27B1 Vitamin D dependent rickets type I Drug metabolism/detoxification Pathway ACADM MCAD Fatty acid oxidation/metabolism ACADVL VLCAD Fatty acid oxidation/metabolism ACSF3 Combined malonic and methylmalonic aciduria Fatty acid oxidation/metabolism CPT1A Hepatic CPT deficiency 1A Fatty acid oxidation/metabolism CPT2 CPT2 deficiency (hepatic/lethal neonatal/myopathy/susceptibiltiy to acute infection-induced encephalopathy) Fatty acid oxidation/metabolism ETFA Glutaric acidemia IIA Fatty acid oxidation/metabolism ETFB Glutaric acidemia IIB Fatty acid oxidation/metabolism ETFDH Glutaric acidemia IIC Fatty acid oxidation/metabolism PANK2 HARP syndrome/neurodegeneration with brain iron accumulation Fatty acid oxidation/metabolism Pathway ALDH1L1 None identified Folate pathway Pathway ALDH1L2 None identified Folate pathway Pathway Page 2 of 14

3 Gene Pathway/Function Association DHFR Megaloblastic anemia Folate pathway Pathway FOLR1 Neurodegeneration due to cerebral folate transport deficiency Folate pathway Both FOLR2 None identified Folate pathway Pathway FPGS None identified Folate pathway Pathway FTCD Glutamate formiminotransferase deficiency Folate pathway Pathway MTHFD1 Susceptibility to abruptio placentae and folate-sensitive neural tube defects Folate pathway Pathway MTHFD1L None identified Folate pathway Pathway MTHFD2L None identified Folate pathway Pathway MTHFR Homocystinuria/susceptibility to thromboembolism, vascular disease, neural tube defects, schizophrenia Folate pathway Pathway MTHFS None identified Folate pathway Pathway MTR Homocystinuria-megaloblastic anemia, cblg complementation type/susceptibility to folate-sensitive neural tube defects Folate pathway Pathway MTRR Homocystinuria-megaloblastic anemia, cbl E type/susceptibility to folate-sensitive neural tube defects Folate pathway Pathway SHMT1 None identified Folate pathway Pathway SHMT2 None identified Folate pathway Pathway SLC19A1 None identified Folate pathway Pathway SLC25A32 Exercise intolerance, riboflavin-responsive Folate pathway Pathway SLC46A1 Hereditary folate malabsorption Folate pathway Pathway DPAGT1 Congenital disorder of glycosylation, type Ij/congenital myasthenic syndrome Glycosylation FKRP Muscular dystrophy-dystroglycanopathy 5 types A, B, C Glycosylation GMPPB Muscular dystrophy-dystroglycanopathy 14 (type A, B, C) Glycosylation MPI Congenital disorder of glycosylation, type Ib Glycosylation PGM1 Congenital disorder of glycosylation, type It Glycosylation PMM2 Congenital disorder of glycosylation, type Ia Glycosylation POMGNT1 Muscular dystrophy-dystroglycanopathy 3 type A, B, C Glycosylation CPOX Coproporphyria/harderoporphyria Heme synthesis PPOX Porphyria variegata Heme synthesis NLRX1 None/PANS Immune response CACNA1A Episodic ataxia/familial hemiplegic migraine/fhm with progressive cerebellar ataxia/spinocerebellar ataxia CACNA1S Hypokalemic periodic paralysis/susceptibility to malignant hypertermia, thyrotoxic periodic paralysis CLCN5 Dent disease/hypophosphatemic rickets/nephrolithiasis type I/proteinuria with hypercalciuric nephrocalcinosis CLCN7 Autosomal dominant/autosomal recessive osteopetrosis CLCNKB Bartter syndrome KCNA1 Episodic ataxia/myokymia syndrome KCNJ2 Andersen syndrome/familial atrial fibrillation/short QT syndrome RYR1 Central core disease/king-denborough syndrome/minicore myopathy with external ophthalmoplegia/euromuscular disease, congenital, with uniform type 1 fiber/malignant hyperthermia susceptibility RYR2 Arrhythmogenic right ventricular dysplasia/catecholaminergic polymorphic ventricular tachycardia/cyclic vomiting syndrome SCN1A Dravet syndrome/generalized epilepsy with febrile seizures plus type 2/familial febrile seizures/familial hemiplegic migraine SCN2A Early infantile epileptic encephalopathy/benign familial infantile seizures SCN4A Hyperkalemic periodic paralysis type 2/hypokalemic periodic paralysis type 2/congenital myasthenic syndrome/atypical acetazolamide-responsive myotonia congenita/paramyotonia congenita SCN5A Familial atrial fibrillation/brugada syndrome/dilated cardiomyopathy/heart block, progressive or non-progressive/long QT syndrome/sick sinus syndrome/familial ventricular fibrillation/susceptibility to SIDS/cyclic vomiting syndrome and functional disease WFS1 Wolfram syndrome/wolfram-like syndrome/autosomal dominant deafness/cataract/association with non-insulin dependent diabetes mellitus Page 3 of 14

4 Gene Pathway/Function Association ATP8B1 Benign familial/progressive/preganacy intrahepatic cholestasis Lipid metabolism/transport DHCR7 Smith-Lemli-Optiz syndrome Lipid metabolism/transport PPT1 Neuronal ceroid lipofuscinosis Lysosomal protein ARSA Metachromatic leukodystrophy Lysosomal protein/enzyme CLN3 Neuronal ceroid lipofuscinosis Lysosomal protein/enzyme CLN6 Neuronal ceroid lipofuscinosis/kufs type (adult onset) Lysosomal protein/enzyme GALC Krabbe disease Lysosomal protein/enzyme GBA Gaucher disease (types neonatal, I, I, III, IIIC)/susceptibility to Lewy body dementia and late onset Parkinson disease Lysosomal protein/enzyme GLA Fabry disease Lysosomal protein/enzyme GNE Sialuria/Nonaka myopathy Lysosomal protein/enzyme HEXB Sandoff disease (infantile, juvenile, adult) Lysosomal protein/enzyme IDS Mucopolysaccharidosis II (Hunter syndrome) Lysosomal protein/enzyme LIPA Cholesterol ester storage disease/wolman disease Lysosomal protein/enzyme NAGA Schindler disease type I, III/Kanzaki disease Lysosomal protein/enzyme NAGLU Charcot-Marie-Tooth disease, axonal, type 2V/mucopolysaccharidosis type IIIB (Sanfilippo B) Lysosomal protein/enzyme PARK2 Parkinson disease, juvenile, type 2 Lysosomal protein/enzyme AHCY Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase Methionine pathway Pathway AK2 Reticular dysgenesis Methionine pathway Pathway BHMT None identified Methionine pathway Pathway CBS B6-responsive and nonresponsive homocystinuria/hyperhomocysteinemic thrombosis Methionine pathway Pathway DMGDH Dimethylglycine dehydrogenase deficiency Methionine pathway Pathway NT5C None identified Methionine pathway Pathway C10ORF2 Mitochondrial DNA depletion syndrome/perrault syndrome/autosomal dominant progressive external ophthalmoplegia Mitochondrial DNA replication Both MGME1 Mitochondrial DNA depletion syndrome Mitochondrial DNA replication Both POLG Mitochondrial DNA depletion syndrome 4A, 4B/mitochondrial recessive ataxia syndrome (SANDO, SCAE)/progressive external ophthalmoplegia AR, AD Mitochondrial DNA replication POLG2 Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions Mitochondrial DNA replication RRM2B Mitochondrial DNA depletion syndrome 8A, 8B/autosomal dominant progressive external opththalmoplegia with mitochondrial DNA deletions Mitochondrial DNA replication TK2 Mitochondrial DNA depletion syndrome 2 (myopathic type) Mitochondrial DNA replication Pathway ACAD9 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway AGK Senger syndrome/mt depletion Mitochondrial electron transport Pathway ATP5C1 None identified Mitochondrial electron transport Pathway ATP5G3 None identified Mitochondrial electron transport Pathway BCS1L Mitochondrial complex III deficiency/leigh syndrome/gracile syndrome/bjornstad syndrome Mitochondrial electron transport Pathway C12ORF65 Combined oxidative phosphorylation deficiency/autosomal recessive spastic paraplegia Mitochondrial electron transport Both CHCHD10 Autosomal dominant isolated mitochondrial myopathy/frontotemporal dementia and/or amyotrophic lateral sclerosis/spinal muscular atrophy, Jokela type Mitochondrial electron transport COX5A None identified Mitochondrial electron transport Pathway COX6C None identified Mitochondrial electron transport Pathway CYC1 Mitochondrial complex III deficiency Mitochondrial electron transport Pathway FOXRED1 Mitochondrial complex I deficiency/leigh syndrome Mitochondrial electron transport Pathway LYRM7 Mitochondrial complex III deficiency Mitochondrial electron transport Pathway MPV17 Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) Mitochondrial electron transport Pathway NDUFA1 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFA11 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFA2 Leigh syndrome due to mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFA9 Leigh syndrome due to mitochondrial complex I deficiency Mitochondrial electron transport Pathway Page 4 of 14

5 Gene Pathway/Function Association NDUFAF1 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFAF2 Mitochondrial complex I deficiency/leigh syndrome Mitochondrial electron transport Pathway NDUFAF3 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFAF4 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFAF5 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFB3 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFB9 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFS1 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFS2 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFS3 Mitochondrial complex I deficiency/leigh syndrome due to mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFS4 Mitochondrial complex I deficiency/leigh syndrome Mitochondrial electron transport Pathway NDUFS6 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFS7 Leigh syndrome Mitochondrial electron transport Pathway NDUFS8 Leigh syndrome due to mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFV1 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFV2 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NUBPL Mitochondrial complex I deficiency Mitochondrial electron transport Both SDHA Dilated cardiomyopathy 1GG/Leigh syndrome/mitochondrial complex II deficiency Mitochondrial electron transport Pathway TTC19 Mitochondrial complex III deficiency Mitochondrial electron transport Both UQCC2 Mitochondrial complex III deficiency Mitochondrial electron transport Pathway UQCRB Mitochondrial complex III deficiency Mitochondrial electron transport Pathway UQCRC2 Mitochondrial complex III deficiency Mitochondrial electron transport Pathway UQCRQ Mitochondrial complex III deficiency Mitochondrial electron transport Pathway CISD2 Wolfram syndrome Mitochondrial other function ISCU Hereditary myopathy with lactic acidosis Mitochondrial other function KIF1B Charcot-Marie-Tooth disease type 2A1 Mitochondrial other function LETM1 None/cyclic vomiting syndrome Mitochondrial other function MFN2 Charcot-Marie-Tooth disease 2A2/hereditary motor and sensory neuropathy VIA Mitochondrial other function PPM1K Maple syrup urine disease, mild variant Mitochondrial other function SLC25A4 Mitochondrial DNA depletion syndrome (cardiomyopathic type)/autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions Mitochondrial other function TAZ Barth syndrome Mitochondrial other function AAAS Achalasia-addisonianism-alacrimia syndrome Neurologic development/function BDNF Central hypoventilation syndrome/mood disorder susceptibility Neurologic development/function DNAJC5 Neuronal ceroid lipofuscinosis/parry type Neurologic development/function GDAP1 Charcot-Marie-Tooth disease (axonal type 2K, axonal with vocal cord paresis, type 4A, recessive intermediate A) Neurologic development/function KIF1A Autosomal dominant ID/hereditary sensory neuropathy type IIC/autosomal recessive spastic paraplegia Neurologic development/function NRXN1 Pitt-Hopkins-like syndrome 2/susceptibility to schizophrenia Neurologic development/function Both PAK3 XL ID Neurologic development/function PTCHD1 X-linked autism susceptibility Neurologic development/function REEP1 Distal hereditary motor neuronopathy type VB/autosomal dominant spastic paraplegia Neurologic development/function SHANK3 Phelan-McDermid syndrome/susceptibility to schizophrenia Neurologic development/function SPTLC2 Neuropathy, hereditary sensory and autonomic, type IC Neurologic development/function SYNGAP1 Autosomal dominant intellectual disability Neurologic development/function AASS Hyperlysinuria/sacchopinuria Neurotransmitter Pathway ABAT GABA-transaminase deficiency Neurotransmitter Pathway ACHE None identified Neurotransmitter Pathway AKR7A2 None identified Neurotransmitter Pathway Page 5 of 14

6 Gene Pathway/Function Association ALDH5A1 Succinic semialdehyde dehydrogenase deficiency Neurotransmitter Pathway CHAT Congenital pre-synaptic myasthenia syndrome/functional disease candidate Neurotransmitter Both CHRNA4 Nocturnal frontal lobe epilepsy/susceptibility to nicotine addiction Neurotransmitter Pathway CHRNB2 Nocturnal frontal lobe epilepsy Neurotransmitter Pathway COMT Susceptibility to mood disorders Neurotransmitter Pathway COMTD1 None identified Neurotransmitter Pathway DBH Dopamine beta hydroxylase deficiency Neurotransmitter Pathway DDC Aromatic L-amino acid decarboxylase deficiency Neurotransmitter Pathway GABRB3 Susceptibility to child absence seizures Neurotransmitter Pathway GAD2 Susceptibility to mood disorders Neurotransmitter Both GCH1 DOPA-responsive dystonia, with or without hyperphenylalaninemia/bh-deficient hyperphenylalaninemia B Neurotransmitter Pathway GLRA1 Hereditary hyperekplexia Neurotransmitter Both HTR2A Susceptibility to mood disorders Neurotransmitter Pathway MAOA Brunner syndrome Neurotransmitter Pathway MAOB None identified Neurotransmitter Pathway NLN None identified Neurotransmitter OAT Gyrate atrophy of choroid and retina with or without ornithinemia Neurotransmitter Pathway PLGRKT Cyclic vomiting syndrome Neurotransmitter PNMT None identified Neurotransmitter Pathway SLC25A22 Early infantile epileptic encephalopathy Neurotransmitter Pathway SLC6A3 Infantile Parkinsonism-dystonia Neurotransmitter Pathway SLC6A4 Susceptibility to mood disorders Neurotransmitter Pathway TH Segawa syndrome Neurotransmitter Pathway TPH1 None identified Neurotransmitter Pathway TPH2 Susceptibility to ADHD, susceptibility to depression Neurotransmitter Pathway BCKDHA Maple syrup urine disease Organic acidemia BCKDHB Maple syrup urine disease Organic acidemia DBT Maple syrup urine disease Organic acidemia ETHE1 Ethylmalonic encephalopathy Organic acidemia GCDH Glutaric aciduria I Organic acidemia IVD Isovaleric acidemia Organic acidemia MCCC1 Isolated MCCC def Organic acidemia MCCC2 3-MCCC def Organic acidemia MLYCD Malonyl-CoA decarboxylase deficiency Organic acidemia MMAA Methylmalonic aciduria, vitamin B12-responsive Organic acidemia MMAB Methylmalonic aciduria, vitamin B12-responsive Organic acidemia MUT Methylmalonic acidemia Organic acidemia PCCA Proprionic acidemia Organic acidemia PCCB Proprionic acidemia Organic acidemia ABCD1 Adrenoleukodystrophy/adrenomyeloneuropathy Peroxisomal protein AGXT Primary hyperoxyluria Peroxisomal protein AMACR Alpha-methylacyl-CoA racemase deficiency/congenital bile acid synthesis defect Peroxisomal protein PEX1 Peroxisome biogenesis disorder 1A, 1B/Heimler syndrome Peroxisomal protein PEX10 Peroxisome biogenesis disorder 6A, 6B Peroxisomal protein PEX12 Peroxisome biogenesis disorder 3A, 3B Peroxisomal protein PEX26 Peroxisome biogenesis disorder 7A, 7B Peroxisomal protein PEX6 Peroxisome biogenesis disorder 4A, 4B/Heimler syndrome Peroxisomal protein PEX7 Peroxisome biogenesis disorder 9B/rhizomelic chondrodysplasia punctata, type 1 Peroxisomal protein Page 6 of 14

7 Gene Pathway/Function Association PHYH Refsum disease Peroxisomal protein SUGCT Glutaric aciduria III Peroxisomal protein DGUOK Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) Purine/pyrimidine/nucleotide pathway Pathway DPYD 5-fluorouracil toxicity/dihydropyrimidine dehydrogenase deficiency Purine/pyrimidine/nucleotide pathway Both HPRT1 Gout, Lesch-Nyhan Purine/pyrimidine/nucleotide pathway PRPS1 Arts syndrome/x-linked recessive Charcot-Marie-Tooth disease/x-linked deafness/prps-related gout/phosphoribosylpyrophosphate synthetase superactivity Purine/pyrimidine/nucleotide pathway TYMP Mitochondrial DNA depletion syndrome 1 (MNGIE type)/determinant of 5-FU toxicity Purine/pyrimidine/nucleotide pathway Both CHD7 CHARGE syndrome/hypogonadotropic hypogonadism with or without anosmia Transcription/translation/replication/repair FMR1 Fragile X syndrome/fragile X tremor/ataxia syndrome/premature ovarian failure Transcription/translation/replication/repair GARS Charcot-Marie-Tooth type 2D/distal hereditary motor neuropathy type VA Transcription/translation/replication/repair HCFC1 Methylmalonic acidemia and homocysteinemia, cblx type (X-linked ID) Transcription/translation/replication/repair MARS Charcot-Marie-Tooth disease 2U, axonal/interstitial lung and liver disease Transcription/translation/replication/repair MECP2 XL ID/Rett syndrome/severe neonatal encephalopathy/xl autism susceptibility Transcription/translation/replication/repair PNKP Ataxia-oculomotor apraxia/microcephaly, seizures, and developmental delay Transcription/translation/replication/repair SIRT1?candidate for mood disorders Transcription/translation/replication/repair Pathway SPRED1 Legius syndrome Transcription/translation/replication/repair TBX1 DiGeorge syndrome/velocardiofacial syndrome/conotruncal anomaly face syndrome/tetralogy of Fallot Transcription/translation/replication/repair DLAT Pyruvate dehydrogenase E2 deficiency Transsulfuration pathway Pathway GSR Hemolytic anemia Transsulfuration pathway Pathway IDH2 D-2-hydroxyglutaric aciduria 2 Transsulfuration pathway Both PDHA1 Pyruvate dehydrogenase E1-alpha deficiency Transsulfuration pathway Pathway PDHB Pyruvate dehydrogenase E1-beta deficiency Transsulfuration pathway Pathway PDHX Lacticacidemia due to PDX1 deficiency Transsulfuration pathway Pathway PDK3 X-linked dominant Charcot-Marie-Tooth disease Transsulfuration pathway Both PDP1 Pyruvate dehydrogenase phosphatase deficiency Transsulfuration pathway Pathway SOD1 Amyotrophic lateral sclerosis Transsulfuration pathway Pathway SOD2 Susceptibility to microvascular diabetes complications Transsulfuration pathway Pathway SUOX Sulfite oxidase deficiency Transsulfuration pathway Pathway ARG1 Argininemia Urea cycle ASL Argininosuccinic aciduria Urea cycle ASS1 Citrullinemia Urea cycle CPS1 Carbamoylphosphate synthetase I deficiency Urea cycle NAGS N-acetylglutamate synthase deficiency Urea cycle OTC Ornithine transcarbamylase deficiency Urea cycle SLC25A15 Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome Urea cycle Page 7 of 14

8 theraseek Panel Gene List by Gene Name Gene Pathway/Function Association AAAS Achalasia-addisonianism-alacrimia syndrome Neurologic development/function AASS Hyperlysinuria/sacchopinuria Neurotransmitter Pathway ABAT GABA-transaminase deficiency Neurotransmitter Pathway ABCD1 Adrenoleukodystrophy/adrenomyeloneuropathy Peroxisomal protein ACAD9 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway ACADM MCAD Fatty acid oxidation/metabolism ACADVL VLCAD Fatty acid oxidation/metabolism ACAT1 Alpha-methylacetoacetic aciduria Amino acid metabolism Pathway ACHE None identified Neurotransmitter Pathway ACSF3 Combined malonic and methylmalonic aciduria Fatty acid oxidation/metabolism ADCK3 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway AGK Senger syndrome/mt depletion Mitochondrial electron transport Pathway AGXT Primary hyperoxyluria Peroxisomal protein AHCY Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase Methionine pathway Pathway AK2 Reticular dysgenesis Methionine pathway Pathway AKR7A2 None identified Neurotransmitter Pathway ALDH1L1 None identified Folate pathway Pathway ALDH1L2 None identified Folate pathway Pathway ALDH3A2 Sjogren-Larsson syndrome Biopterin pathway Pathway ALDH5A1 Succinic semialdehyde dehydrogenase deficiency Neurotransmitter Pathway AMACR Alpha-methylacyl-CoA racemase deficiency/congenital bile acid synthesis defect Peroxisomal protein ANK2 Cardiac arrhythmia, ankyrin-b-related/long QT syndrome/autism/functional disease candidate Cytoskeleton/extracellular matrix APTX Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia Coenzyme q10/nadph pathway Pathway ARG1 Argininemia Urea cycle ARSA Metachromatic leukodystrophy Lysosomal protein/enzyme ASL Argininosuccinic aciduria Urea cycle ASS1 Citrullinemia Urea cycle ATP5C1 None identified Mitochondrial electron transport Pathway ATP5G3 None identified Mitochondrial electron transport Pathway ATP7A Menkes disease/occipital horn disease/x-linked distal Spinal muscular atrophy Cofactor or metal disorder ATP8B1 Benign familial/progressive/preganacy intrahepatic cholestasis Lipid metabolism/transport BCKDHA Maple syrup urine disease Organic acidemia BCKDHB Maple syrup urine disease Organic acidemia BCS1L Mitochondrial complex III deficiency/leigh syndrome/gracile syndrome/bjornstad syndrome Mitochondrial electron transport Pathway BDNF Central hypoventilation syndrome/mood disorder susceptibility Neurologic development/function BHMT None identified Methionine pathway Pathway BTD Biotinidase deficiency Cofactor or metal disorder Pathway C10ORF2 Mitochondrial DNA depletion syndrome/perrault syndrome/autosomal dominant progressive external ophthalmoplegia Mitochondrial DNA replication Both C12ORF65 Combined oxidative phosphorylation deficiency/autosomal recessive spastic paraplegia Mitochondrial electron transport Both CACNA1A Episodic ataxia/familial hemiplegic migraine/fhm with progressive cerebellar ataxia/spinocerebellar ataxia CACNA1S Hypokalemic periodic paralysis/susceptibility to malignant hypertermia, thyrotoxic periodic paralysis CBS B6-responsive and nonresponsive homocystinuria/hyperhomocysteinemic thrombosis Methionine pathway Pathway CHAT Congenital pre-synaptic myasthenia syndrome/functional disease candidate Neurotransmitter Both Page 8 of 14

9 Gene Pathway/Function Association CHCHD10 Autosomal dominant isolated mitochondrial myopathy/frontotemporal dementia and/or amyotrophic lateral sclerosis/spinal muscular atrophy, Jokela type Mitochondrial electron transport CHD7 CHARGE syndrome/hypogonadotropic hypogonadism with or without anosmia Transcription/translation/replication/repair CHRNA4 Nocturnal frontal lobe epilepsy/susceptibility to nicotine addiction Neurotransmitter Pathway CHRNB2 Nocturnal frontal lobe epilepsy Neurotransmitter Pathway CISD2 Wolfram syndrome Mitochondrial other function CLCN5 Dent disease/hypophosphatemic rickets/nephrolithiasis type I/proteinuria with hypercalciuric nephrocalcinosis CLCN7 Autosomal dominant/autosomal recessive osteopetrosis CLCNKB Bartter syndrome CLN3 Neuronal ceroid lipofuscinosis Lysosomal protein/enzyme CLN6 Neuronal ceroid lipofuscinosis/kufs type (adult onset) Lysosomal protein/enzyme COMT Susceptibility to mood disorders Neurotransmitter Pathway COMTD1 None identified Neurotransmitter Pathway COQ10B None identified Coenzyme q10/nadph pathway Pathway COQ2 Primary Coenzyme Q10 deficiency/susceptibility to multiple system atrophy Coenzyme q10/nadph pathway Pathway COQ3 None identified Coenzyme q10/nadph pathway Pathway COQ4 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway COQ5 None identified Coenzyme q10/nadph pathway Pathway COQ6 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway COQ7 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway COQ9 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway COX5A None identified Mitochondrial electron transport Pathway COX6C None identified Mitochondrial electron transport Pathway CPOX Coproporphyria/harderoporphyria Heme synthesis CPS1 Carbamoylphosphate synthetase I deficiency Urea cycle CPT1A Hepatic CPT deficiency 1A Fatty acid oxidation/metabolism CPT2 CPT2 deficiency (hepatic/lethal neonatal/myopathy/susceptibiltiy to acute infection-induced encephalopathy) Fatty acid oxidation/metabolism CYBA Chronic granulomatous disease Coenzyme q10/nadph pathway CYBB Chronic granulomatous disease Coenzyme q10/nadph pathway CYC1 Mitochondrial complex III deficiency Mitochondrial electron transport Pathway CYP27A1 Cerebrotendinous xanthomatosis Drug metabolism/detoxification Pathway CYP27B1 Vitamin D dependent rickets type I Drug metabolism/detoxification Pathway DBH Dopamine beta hydroxylase deficiency Neurotransmitter Pathway DBT Maple syrup urine disease Organic acidemia DDAH1 None identified Biopterin pathway Pathway DDC Aromatic L-amino acid decarboxylase deficiency Neurotransmitter Pathway DGUOK Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) Purine/pyrimidine/nucleotide pathway Pathway DHCR7 Smith-Lemli-Optiz syndrome Lipid metabolism/transport DHFR Megaloblastic anemia Folate pathway Pathway DHTKD1 Charcot-Marie-Tooth disease 2Q, axonal/2-aminoadipic 2-oxoadipic aciduria Amino acid metabolism DLAT Pyruvate dehydrogenase E2 deficiency Transsulfuration pathway Pathway DMD Duchenne muscular dystrophy/becker muscular dystrophy/dilated cardiomyopathy Cytoskeleton/extracellular matrix DMGDH Dimethylglycine dehydrogenase deficiency Methionine pathway Pathway DNAJC5 Neuronal ceroid lipofuscinosis/parry type Neurologic development/function DPAGT1 Congenital disorder of glycosylation, type Ij/congenital myasthenic syndrome Glycosylation DPYD 5-fluorouracil toxicity/dihydropyrimidine dehydrogenase deficiency Purine/pyrimidine/nucleotide pathway Both ELN Cutis laxa/supravalvar aortic stenosis Cytoskeleton/extracellular matrix ETFA Glutaric acidemia IIA Fatty acid oxidation/metabolism Page 9 of 14

10 Gene Pathway/Function Association ETFB Glutaric acidemia IIB Fatty acid oxidation/metabolism ETFDH Glutaric acidemia IIC Fatty acid oxidation/metabolism ETHE1 Ethylmalonic encephalopathy Organic acidemia FKRP Muscular dystrophy-dystroglycanopathy 5 types A, B, C Glycosylation FLNA Otopalatodigital syndrome types I and II, congenital short bowel syndrome, X-linked cardiac valvular dysplasia, Melnick- Needles, frontometaphyseal dysplasia, periventricular heterotopia, FG syndrome 2 Cytoskeleton/extracellular matrix FMR1 Fragile X syndrome/fragile X tremor/ataxia syndrome/premature ovarian failure Transcription/translation/replication/repair FOLR1 Neurodegeneration due to cerebral folate transport deficiency Folate pathway Both FOLR2 None identified Folate pathway Pathway FOXRED1 Mitochondrial complex I deficiency/leigh syndrome Mitochondrial electron transport Pathway FPGS None identified Folate pathway Pathway FTCD Glutamate formiminotransferase deficiency Folate pathway Pathway G6PC Glycogen storage disease type 1A Carbohydrate metabolism G6PD Favism/hemolytic anemia Biopterin pathway Both GABRB3 Susceptibility to child absence seizures Neurotransmitter Pathway GAD2 Susceptibility to mood disorders Neurotransmitter Both GALC Krabbe disease Lysosomal protein/enzyme GAMT Cerebral creatine deficiency syndrome 2 Amino acid metabolism GARS Charcot-Marie-Tooth type 2D/distal hereditary motor neuropathy type VA Transcription/translation/replication/repair GATM Cerebral creatine deficiency syndrome 3 Amino acid metabolism GBA Gaucher disease (types neonatal, I, I, III, IIIC)/susceptibility to Lewy body dementia and late onset Parkinson disease Lysosomal protein/enzyme GCDH Glutaric aciduria I Organic acidemia GCH1 DOPA-responsive dystonia, with or without hyperphenylalaninemia/bh-deficient hyperphenylalaninemia B Neurotransmitter Pathway GDAP1 Charcot-Marie-Tooth disease (axonal type 2K, axonal with vocal cord paresis, type 4A, recessive intermediate A) Neurologic development/function GIF Intrinsic factor deficiency Cofactor or metal disorder Both GK Glycerol kinase deficiency Carbohydrate metabolism Both GLA Fabry disease Lysosomal protein/enzyme GLRA1 Hereditary hyperekplexia Neurotransmitter Both GLRX None identified Antioxidant pathway Pathway GLRX2 None identified Antioxidant pathway Pathway GLRX5 3, pyridoxine-refractory sideroblastic anemia/childhood-onset spasticity with hyperglycinemia Antioxidant pathway Pathway GMPPB Muscular dystrophy-dystroglycanopathy 14 (type A, B, C) Glycosylation GNAS Pseudohypoparathyroidism (Ia, Ib, Ic)/pseudopseudohypoparathyroidism/progressive osseous heteroplasia Cell signaling pathway GNE Sialuria/Nonaka myopathy Lysosomal protein/enzyme GPI Nonspherocytic hemolytic anemia Carbohydrate metabolism GPX1 Hemolytic anemia Antioxidant pathway Pathway GSR Hemolytic anemia Transsulfuration pathway Pathway GSTK1 None identified Antioxidant pathway Pathway HCFC1 Methylmalonic acidemia and homocysteinemia, cblx type (X-linked ID) Transcription/translation/replication/repair HEXB Sandoff disease (infantile, juvenile, adult) Lysosomal protein/enzyme HK1 Hereditary motor and sensor neuropathyy, Russe type/hemolytic anemia Carbohydrate metabolism HK3 None/PANS Carbohydrate metabolism HPRT1 Gout, Lesch-Nyhan Purine/pyrimidine/nucleotide pathway HTR2A Susceptibility to mood disorders Neurotransmitter Pathway IDH2 D-2-hydroxyglutaric aciduria 2 Transsulfuration pathway Both IDS Mucopolysaccharidosis II (Hunter syndrome) Lysosomal protein/enzyme ISCU Hereditary myopathy with lactic acidosis Mitochondrial other function IVD Isovaleric acidemia Organic acidemia Page 10 of 14

11 Gene Pathway/Function Association KCNA1 Episodic ataxia/myokymia syndrome KCNJ2 Andersen syndrome/familial atrial fibrillation/short QT syndrome KIF1A Autosomal dominant ID/hereditary sensory neuropathy type IIC/autosomal recessive spastic paraplegia Neurologic development/function KIF1B Charcot-Marie-Tooth disease type 2A1 Mitochondrial other function LDHA Glycogen storage disease XI Carbohydrate metabolism LETM1 None/cyclic vomiting syndrome Mitochondrial other function LIPA Cholesterol ester storage disease/wolman disease Lysosomal protein/enzyme LYRM7 Mitochondrial complex III deficiency Mitochondrial electron transport Pathway MAOA Brunner syndrome Neurotransmitter Pathway MAOB None identified Neurotransmitter Pathway MARS Charcot-Marie-Tooth disease 2U, axonal/interstitial lung and liver disease Transcription/translation/replication/repair MCCC1 Isolated MCCC def Organic acidemia MCCC2 3-MCCC def Organic acidemia MECP2 XL ID/Rett syndrome/severe neonatal encephalopathy/xl autism susceptibility Transcription/translation/replication/repair MFN2 Charcot-Marie-Tooth disease 2A2/hereditary motor and sensory neuropathy VIA Mitochondrial other function MGME1 Mitochondrial DNA depletion syndrome Mitochondrial DNA replication Both MLYCD Malonyl-CoA decarboxylase deficiency Organic acidemia MMAA Methylmalonic aciduria, vitamin B12-responsive Organic acidemia MMAB Methylmalonic aciduria, vitamin B12-responsive Organic acidemia MPI Congenital disorder of glycosylation, type Ib Glycosylation MPV17 Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) Mitochondrial electron transport Pathway MSRA None identified Antioxidant pathway Pathway MSRB2 None identified Antioxidant pathway Pathway MTHFD1 Susceptibility to abruptio placentae and folate-sensitive neural tube defects Folate pathway Pathway MTHFD1L None identified Folate pathway Pathway MTHFD2L None identified Folate pathway Pathway MTHFR Homocystinuria/susceptibility to thromboembolism, vascular disease, neural tube defects, schizophrenia Folate pathway Pathway MTHFS None identified Folate pathway Pathway MTR Homocystinuria-megaloblastic anemia, cblg complementation type/susceptibility to folate-sensitive neural tube defects Folate pathway Pathway MTRR Homocystinuria-megaloblastic anemia, cbl E type/susceptibility to folate-sensitive neural tube defects Folate pathway Pathway MUT Methylmalonic acidemia Organic acidemia NAGA Schindler disease type I, III/Kanzaki disease Lysosomal protein/enzyme NAGLU Charcot-Marie-Tooth disease, axonal, type 2V/mucopolysaccharidosis type IIIB (Sanfilippo B) Lysosomal protein/enzyme NAGS N-acetylglutamate synthase deficiency Urea cycle NDUFA1 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFA11 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFA2 Leigh syndrome due to mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFA9 Leigh syndrome due to mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFAF1 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFAF2 Mitochondrial complex I deficiency/leigh syndrome Mitochondrial electron transport Pathway NDUFAF3 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFAF4 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFAF5 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFB3 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFB9 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFS1 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFS2 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFS3 Mitochondrial complex I deficiency/leigh syndrome due to mitochondrial complex I deficiency Mitochondrial electron transport Pathway Page 11 of 14

12 Gene Pathway/Function Association NDUFS4 Mitochondrial complex I deficiency/leigh syndrome Mitochondrial electron transport Pathway NDUFS6 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFS7 Leigh syndrome Mitochondrial electron transport Pathway NDUFS8 Leigh syndrome due to mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFV1 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NDUFV2 Mitochondrial complex I deficiency Mitochondrial electron transport Pathway NLN None identified Neurotransmitter NLRX1 None/PANS Immune response NOS3 Susceptibility to late-onset Alzheimer disease, coronary artery spasm, hypertension, ischemic stroke, pregnancyinduced hypertension, placental abruption/vascular functional disease (migraine, POTS, stroke-like episodes) Biopterin pathway Both NRXN1 Pitt-Hopkins-like syndrome 2/susceptibility to schizophrenia Neurologic development/function Both NT5C None identified Methionine pathway Pathway NUBPL Mitochondrial complex I deficiency Mitochondrial electron transport Both OAT Gyrate atrophy of choroid and retina with or without ornithinemia Neurotransmitter Pathway OTC Ornithine transcarbamylase deficiency Urea cycle OXR1 None identified Antioxidant pathway Pathway PAH Phenylketonuria/hyperphenylalaninemia Biopterin pathway Both PAK3 XL ID Neurologic development/function PANK2 HARP syndrome/neurodegeneration with brain iron accumulation Fatty acid oxidation/metabolism Pathway PARK2 Parkinson disease, juvenile, type 2 Lysosomal protein/enzyme PARK7 Autosomal recessive early-onset Parkinson disease Antioxidant pathway Pathway PCCA Proprionic acidemia Organic acidemia PCCB Proprionic acidemia Organic acidemia PDHA1 Pyruvate dehydrogenase E1-alpha deficiency Transsulfuration pathway Pathway PDHB Pyruvate dehydrogenase E1-beta deficiency Transsulfuration pathway Pathway PDHX Lacticacidemia due to PDX1 deficiency Transsulfuration pathway Pathway PDK3 X-linked dominant Charcot-Marie-Tooth disease Transsulfuration pathway Both PDP1 Pyruvate dehydrogenase phosphatase deficiency Transsulfuration pathway Pathway PDSS1 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway PDSS2 Primary Coenzyme Q10 deficiency Coenzyme q10/nadph pathway Pathway PEX1 Peroxisome biogenesis disorder 1A, 1B/Heimler syndrome Peroxisomal protein PEX10 Peroxisome biogenesis disorder 6A, 6B Peroxisomal protein PEX12 Peroxisome biogenesis disorder 3A, 3B Peroxisomal protein PEX26 Peroxisome biogenesis disorder 7A, 7B Peroxisomal protein PEX6 Peroxisome biogenesis disorder 4A, 4B/Heimler syndrome Peroxisomal protein PEX7 Peroxisome biogenesis disorder 9B/rhizomelic chondrodysplasia punctata, type 1 Peroxisomal protein PGAM2 Glycogen storage disease X Carbohydrate metabolism PGK1 Phosphoglycerate kinase 1 deficiency Carbohydrate metabolism PGM1 Congenital disorder of glycosylation, type It Glycosylation PHYH Refsum disease Peroxisomal protein PINK1 Early onset Parkinson disease Antioxidant pathway Pathway PKLR Pyruvate kinase deficiency Carbohydrate metabolism PLGRKT Cyclic vomiting syndrome Neurotransmitter PMM2 Congenital disorder of glycosylation, type Ia Glycosylation PNKD Paroxysmal nonkinesigenic dyskinesia Antioxidant pathway PNKP Ataxia-oculomotor apraxia/microcephaly, seizures, and developmental delay Transcription/translation/replication/repair PNMT None identified Neurotransmitter Pathway Page 12 of 14

13 Gene Pathway/Function Association POLG Mitochondrial DNA depletion syndrome 4A, 4B/mitochondrial recessive ataxia syndrome (SANDO, SCAE)/progressive external ophthalmoplegia AR, AD Mitochondrial DNA replication POLG2 Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions Mitochondrial DNA replication POMGNT1 Muscular dystrophy-dystroglycanopathy 3 type A, B, C Glycosylation PPM1K Maple syrup urine disease, mild variant Mitochondrial other function PPOX Porphyria variegata Heme synthesis PPT1 Neuronal ceroid lipofuscinosis Lysosomal protein PRDX1 None identified Antioxidant pathway Pathway PRDX2 None identified Antioxidant pathway Pathway PRDX3 None identified Antioxidant pathway Pathway PRDX5 None identified Antioxidant pathway Pathway PRDX6 None identified Antioxidant pathway Pathway PRPS1 Arts syndrome/x-linked recessive Charcot-Marie-Tooth disease/x-linked deafness/prps-related gout/phosphoribosylpyrophosphate synthetase superactivity Purine/pyrimidine/nucleotide pathway PTCHD1 X-linked autism susceptibility Neurologic development/function PTS BH4-deficient hyperphenylalaninemia A Biopterin pathway QDPR BH4-deficient hyperphenylalaninemia C Biopterin pathway REEP1 Distal hereditary motor neuronopathy type VB/autosomal dominant spastic paraplegia Neurologic development/function RRM2B Mitochondrial DNA depletion syndrome 8A, 8B/autosomal dominant progressive external opththalmoplegia with mitochondrial DNA deletions Mitochondrial DNA replication RYR1 Central core disease/king-denborough syndrome/minicore myopathy with external ophthalmoplegia/euromuscular disease, congenital, with uniform type 1 fiber/malignant hyperthermia susceptibility RYR2 Arrhythmogenic right ventricular dysplasia/catecholaminergic polymorphic ventricular tachycardia/cyclic vomiting syndrome SCN1A Dravet syndrome/generalized epilepsy with febrile seizures plus type 2/familial febrile seizures/familial hemiplegic migraine SCN2A Early infantile epileptic encephalopathy/benign familial infantile seizures SCN4A Hyperkalemic periodic paralysis type 2/hypokalemic periodic paralysis type 2/congenital myasthenic syndrome/atypical acetazolamide-responsive myotonia congenita/paramyotonia congenita SCN5A Familial atrial fibrillation/brugada syndrome/dilated cardiomyopathy/heart block, progressive or non-progressive/long QT syndrome/sick sinus syndrome/familial ventricular fibrillation/susceptibility to SIDS/cyclic vomiting syndrome and functional disease SDHA Dilated cardiomyopathy 1GG/Leigh syndrome/mitochondrial complex II deficiency Mitochondrial electron transport Pathway SHANK3 Phelan-McDermid syndrome/susceptibility to schizophrenia Neurologic development/function SHMT1 None identified Folate pathway Pathway SHMT2 None identified Folate pathway Pathway SIRT1?candidate for mood disorders Transcription/translation/replication/repair Pathway SLC16A1 Erythrocyte lactate transporter defect/familial hyperinsulinemic hypoglycemia/monocarboxylate transporter 1 deficiency Carbohydrate metabolism SLC19A1 None identified Folate pathway Pathway SLC22A5 Systemic primary carnitine deficiency Carnitine metabolism Pathway SLC25A15 Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome Urea cycle SLC25A22 Early infantile epileptic encephalopathy Neurotransmitter Pathway SLC25A32 Exercise intolerance, riboflavin-responsive Folate pathway Pathway SLC25A4 Mitochondrial DNA depletion syndrome (cardiomyopathic type)/autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions Mitochondrial other function SLC2A1 GLUT1 deficiency syndrome 1 and 2/stomatin-deficient cryohydrocytosis with neurologic defects/dystonia/susceptibility to generalized epilepsy Carbohydrate metabolism SLC46A1 Hereditary folate malabsorption Folate pathway Pathway Page 13 of 14

14 Gene Pathway/Function Association SLC6A3 Infantile Parkinsonism-dystonia Neurotransmitter Pathway SLC6A4 Susceptibility to mood disorders Neurotransmitter Pathway SLC6A8 Cerebral creatine deficiency syndrome Amino acid metabolism SOD1 Amyotrophic lateral sclerosis Transsulfuration pathway Pathway SOD2 Susceptibility to microvascular diabetes complications Transsulfuration pathway Pathway SPAST Autosomal dominant spastic paraplegia Cytoskeleton/extracellular matrix SPR DOPA-responsive dystonia Biopterin pathway Both SPRED1 Legius syndrome Transcription/translation/replication/repair SPTLC2 Neuropathy, hereditary sensory and autonomic, type IC Neurologic development/function SUGCT Glutaric aciduria III Peroxisomal protein SUOX Sulfite oxidase deficiency Transsulfuration pathway Pathway SYNGAP1 Autosomal dominant intellectual disability Neurologic development/function TAZ Barth syndrome Mitochondrial other function TBX1 DiGeorge syndrome/velocardiofacial syndrome/conotruncal anomaly face syndrome/tetralogy of Fallot Transcription/translation/replication/repair TH Segawa syndrome Neurotransmitter Pathway TK2 Mitochondrial DNA depletion syndrome 2 (myopathic type) Mitochondrial DNA replication Pathway TMLHE Epsilon-trimethyllysine hydroxylase deficiency Carnitine metabolism Both TPH1 None identified Neurotransmitter Pathway TPH2 Susceptibility to ADHD, susceptibility to depression Neurotransmitter Pathway TPK1 Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) Cofactor or metal disorder Pathway TRAP1 Functional disease Antioxidant pathway Both TSC1 Tuberous sclerosis/focal cortical dysplasia, Taylor balloon cell type Cell signaling pathway TSC2 Tuberous sclerosis Cell signaling pathway TTC19 Mitochondrial complex III deficiency Mitochondrial electron transport Both TYMP Mitochondrial DNA depletion syndrome 1 (MNGIE type)/determinant of 5-FU toxicity Purine/pyrimidine/nucleotide pathway Both UQCC2 Mitochondrial complex III deficiency Mitochondrial electron transport Pathway UQCRB Mitochondrial complex III deficiency Mitochondrial electron transport Pathway UQCRC2 Mitochondrial complex III deficiency Mitochondrial electron transport Pathway UQCRQ Mitochondrial complex III deficiency Mitochondrial electron transport Pathway VDR Vitamin D-resistant rickets type IIA Cofactor or metal disorder Both WFS1 Wolfram syndrome/wolfram-like syndrome/autosomal dominant deafness/cataract/association with non-insulin dependent diabetes mellitus Page 14 of 14