Table 6. Genes associated with amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, or vascular cognitive impairment as represented on the ONDRISeq targeted resequencing panel.
| Gene | Chromosomal location | Affected protein | Associated phenotype | Mode of inheritance | OMIM numbers (locus, phenotype) |
|---|---|---|---|---|---|
|
Amyotrophic lateral sclerosis/frontotemporal dementia | |||||
| ALS2 | 2q33.1 | Alsin | ALS2 | AR (HZ), juvenile onset | 606352, 205100 |
| ANG | 14q11.2 | Angiogenin | ALS9 | ADm, late onset | 105850, 611895 |
| ARHGEF28 | 5q13.2 | Rho guanine nucleotide exchange factor 28 | ALS and FTD | AR (HZ) and ADm, late onset | 612790, PMID: 23286752 (phenotype not updated on OMIM) |
| ATXN2 | 12q24.12 | Ataxin 2 | ALS13 | ADm, late onset | 601517, 183090 |
| CENPV | 17p11.2 | Centromere protein V | ALS | Genetic association, late onset | 608139, PMID: 22959728 (phenotype not updated on OMIM) |
| CHMP2B | 3p11.2 | CHMP family member 2B | ALS17, FTD | ADm, late onset | 609512, 614696 |
| DAO | 12q24.11 | D-amino acid oxidase | ALS, schizophrenia | ADm, late onset | 124050, 105400, 181500 |
| DCTN1 | 2p13.1 | Dynactin 1 | ALS, HMN7B, Perry syndrome | ADm, late onset | 601143, 105400, 607641, 168605 |
| FIG4 | 6q21 | FIG4 homologue, SAC1 lipid phosphatase domain containing | ALS11, CMT disease, YV syndrome | ADm, late onset; AR (HZ and CH), infantile onset; AR (HZ and CH), infantile onset | 609390, 612577, 611228, 216340 |
| FUS | 16p11.2 | Fused in sarcoma | ALS6, FTD, HET4 | AR (HZ), ADm, late onset | 137070, 608030, 614782 |
| GRN | 17q21.31 | Granulin precursor | FTD, NCL | ADm, late onset; AR (HZ), juvenile onset | 138945, 607485, 614706 |
| HNRNPA1 | 12q13.13 | Heterogeneous nuclear ribonucleoprotein A1 | ALS20, inclusion body myopathy with early-onset Paget disease with/without FTD 3 | ADm, late onset; ADm, early onset | 164017, 615426, 615424 |
| HNRNPA2B1 | 7p15.2 | Heterogeneous nuclear ribonucleoprotein A2/B1 | Inclusion body myopathy with early-onset Paget disease with/without FTD 2 | ADm, early onset | 600124, 615422 |
| MAPT/STH | 17q21.31 | Microtubule-associated protein tau | ALS, FTD with parkinsonism, PD, AD, Pick disease, supranuclear palsy, tauopathy | ADm, late and early onset | 157140, 105400, 600274, 168600, 104300, 172700, 601104, 260540 |
| NEFH | 22q12.2 | Neurofilament protein, heavy polypeptide | ALS1 | ADm, late onset | 162230, 105400 |
| OPTN | 10p13 | Optineurin | ALS12, glaucoma | AR (HZ) and AD, early onset | 602432, 613435, 606657 |
| PFN1 | 17p13.2 | Profilin 1 | ALS18 | ADm, earlier onset | 176610, 614808 |
| PNPLA6 | 19p13.2 | Patatin-like phospholipase domain-containing protein 6 | Spastic paraplegia, Boucher-Neuhauser syndrome | AR (HZ and CH), early onset | 603197, 612020, 215470 |
| PRPH | 12q13.12 | Peripherin | ALS1 | ADm, late onset | 170710, 105400 |
| SETX | 9q34.13 | Senataxin | ALS4, spinocerebellar ataxia 1 | ADm and AR, juvenile onset | 608465, 602433, 606002 |
| SIGMAR1 | 9p13.3 | Sigma nonopioid intracellular receptor 1 | ALS16, FTD | AR (HZ); ADm, early onset | 601978, 614373, 105550 |
| SOD1 | 21q22.11 | Superoxide dismutase 1 | ALS1 | AR (HZ and CH), ADm, age of onset varies from 6–94 years old | 147450, 105400 |
| SQSTM1 | 5q35.3 | Sequestosome 1 | Paget disease of bone | ADm, late onset | 601530, 167250 |
| TAF15 | 17q12 | TAF15 RNA polymerase II, TATA box-binding protein-associated factor | Chondrosarcoma | 601574, 612237 | |
| TARDBP | 1p36.22 | Tar DNA-binding protein | ALS10, FTD | ADm, late onset | 605078, 612069 |
| UBQLN2 | Xp11.21 | Ubiquilin 2 | ALS15, FTD | X-linked, juvenile and late onset | 300264, 300857 |
| UNC13A | 19p13.11 | Unc-13 homolog A (C. elegans) | ALS | Genetic association, late onset | 609894, PMID: 22921269 (phenotype not updated on OMIM) |
| VAPB | 20q13.33 | Vesicle-associated membrane protein (VAMP)-associated protein B and C | ALS, spinal muscular atrophy (Finkel type) | ADm, early and late onset | 605704, 608627, 182980 |
| VCP | 9p13.3 | Valosin-containing protein | ALS14, FTD, inclusion body myopathy with early-onset Paget disease with/without FTD 1 | ADm, early onset | 601023, 613954, 167320 |
|
Alzheimer’s disease/mild cognitive impairment | |||||
| ABCA7 | 19p13.3 | ATP-binding cassette, subfamily a, member 7 | AD | Genetic association, late onset | 605414, 104300 |
| APOE | 19q13.32 | Apolipoprotein E | AD2, lipoprotein glomerulopathy, sea-blue hystiocyte disease, macular degeneration | ACD, ADm, AR (HZ and CH), late onset | 107741, 104310, 611771, 269600, 603075 |
| APP | 21q21.3 | Amyloid beta A4 precursor protein | AD 1, cerebral amyloid angiopathy | ADm and AR (HZ), early and late onset | 104760, 104300, 605714 |
| BIN1 | 2q14.3 | Bridging integrator 1 | AD | Genetic association, late onset | 601248, PMID: 25365775 (phenotype not updated on OMIM) |
| CD2AP | 6p12.3 | CD2-associated protein | AD | Genetic association, late onset | 604241, PMID: 25092125 (phenotype not updated on OMIM) |
| CD33 | 19q13.41 | CD33 antigen | AD | Genetic association, late onset | 159590, PMID: 23982747 (phenotype not updated on OMIM) |
| CLU | 8p21.1 | Clusterin | AD | Genetic association, late onset | 185430, PMID: 25189118 (phenotype not updated on OMIM) |
| CR1 | 1q32.2 | Complement component receptor 1 | AD | Genetic association, late onset | 120620, PMID: 25022885 (phenotype not updated on OMIM) |
| CSF1R | 5q32 | Colony-stimulating factor 1 receptor | HDLS with dementia | ADm, early and late onset | 164770, 221820 |
| DNMT1 | 19p13.2 | DNA methyltransferase 1 | HSN1E with dementia | ADm, early onset dementia | 126375, 614116 |
| ITM2B | 13q14.2 | Integral membrane protein 2B | Dementia | ADm, early and late onset | 603904, 176500, 117300 |
| MS4A4E | 11q12.2 | Membrane-spanning 4-domains, subfamily A, member 4E | AD | Genetic association, late onset | 608401, PMID: 21460840 (phenotype not updated on OMIM) |
| MS4A6A | 11q12.2 | Membrane-spanning 4-domains, subfamily A, member 6A | AD | Genetic association, late onset | 606548, PMID: 21460840 (phenotype not updated on OMIM) |
| PICALM | 11q14.2 | Phosphatidylinositol-binding clathrin assembly protein | AD | Genetic association, late onset | 603025, PMID: 24613704 (phenotype not updated on OMIM) |
| PLD3 | 19q13.2 | Phospholipase D family, member 3 | AD19 | Genetic association, late onset | 615698, 615711 |
| PSEN1 | 14q24.2 | Presenilin 1 | AD3, dilated cardiomyopathy, FTD, Pick disease, acne inversa | ADm, early onset | 104311, 607822, 613694, 600274, 172700, 613737 |
| PRNP | 20p13 | Prion protein | Dementia | ADm, early onset | 176640, 606688 |
| PSEN2 | 1q32.13 | Presenilin 2 | AD4, dilated cardiomyopathy | ADm, early onset | 600759, 606889, 613697 |
| SORL1 | 11q24.1 | Sortilin-related receptor | AD | ADm, combined gene burden, late onset | 602005, 104300; PMID: 25382023 (phenotype not updated on OMIM) |
| TREM2 | 6p21.1 | Triggering receptor expressed on myeloid cells 2 | AD Nasu-Hakola disease (dementia and psychotic symptoms) | Genetic association, late onset | 605086, PMID: 25596843 (phenotype not updated on OMIM), 221770 |
| TYROBP | 19q13.12 | Tyro protein tyrosine kinase-binding protein | Nasu–Hakola disease (dementia and psychotic symptoms) | AR (HZ), juvenile onset | 604142, 221770 |
|
Parkinson’s disease | |||||
| ADH1C | 4q23 | Alcohol dehydrogenase 1C, gamma polypeptide | PD, alcohol dependence protection | Genetic association, late onset | 103730, 168600, 103780 |
| ATP13A2 (PARK9) | 1p36.13 | ATPase, type 13A2 | PD, ceroid lipofuscinosis, dementia | Genetic association, early onset and late onset | 610513, 606693 |
| DNAJC13 | 3q22.1 | DNAJ/HSP40 homolog, subfamily C, member 13 | PD | ADm, late onset | 614334, PMID: 25330418 (phenotype not updated on OMIM) |
| EIF4G1 | 3q27.1 | Eukaryotic translation initiation factor 4-gamma | PD18 | ADm, late onset | 600495, 614251 |
| FBXO7 | 22q12.3 | F-box only protein 7 | PD15 | AR (HZ and CH), early onset | 605648, 260300 |
| GAK | 4p16.3 | Cyclin G-associated kinase | PD | Genetic association, late onset | 602052, PMID: 21258085 (phenotype not updated on OMIM) |
| GCH1 | 14q22.2 | GTP cyclohydrolase I | PD, dystonia | Genetic association, early onset | 600225, 128230 |
| GIGYF2 | 2q37.1 | GRB10-interacting GYP protein 2 | PD11 | Genetic association, early and late onset | 612003, 607688 |
| HTRA2 | 2p13.1 | HTRA serine peptidase 2 | PD13 | ADm and genetic association, early and late onset | 606441, 610297 |
| LRRK2 | 12q12 | Leucine-rich repeat kinase 2 | PD8 | ADm and genetic association, early and late onset | 609007, 607060 |
| MC1R | 16q24.3 | Melanocortin 1 receptor | PD; melanoma, UV induced skin damage | Genetic association, late onset | 155555, 613099, 266300, 168600 |
| NR4A2 | 2q24.1 | Nuclear receptor subfamily 4, group A, member 2 | PD | Genetic association, late onset | 601828, 168600 |
| PANK2 | 20p13 | Pantothenate kinase 2 | Neurodegeneration | AR (HZ and CH), early onset | 606157, 234200 |
| PARK2 (PRKN) | 6q26 | Parkin | PD2 | AR (HZ and CH), juvenile onset; heterozygotes have late onset | 602544, 600116 |
| PARK7(DJ1) | 1p36.23 | Oncogene DJ1 | PD7 | AR (HZ and CH), early onset | 602533, 606324 |
| PARL | 3q27.1 | Presenilin-associated rhomboid-like protein | PD (based on biological mechanisms, no linkage confirmed) | NA | 607858, PMID: 21355049 (phenotype not updated on OMIM) |
| PINK1 | 1p36.12 | Pten-induced putative kinase 1 | PD6 | AR (HZ and CH), ADm, early onset | 608309, 605909 |
| PLA2G6 | 22q13.1 | Phospholipase A2, group VI | PD14, NBIA2A, NBIA2B | AR (HZ and CH), early and late onset | 603604, 612953, 256600, 610217 |
| PM20D1 | 1q32 | Peptidase M20 domain containing 1 | PD16 | Genetic association, late onset | Locus ID not available on OMIM, 613164 |
| RAB7L1 | 1q32.1 | RAB7-like 1 | PD | Genetic association, late onset | 603949, PMID: 25040112 (phenotype not updated on OMIM) |
| SNCA | 4q22.1 | Alpha-synuclein | PD1, PD4, LBD | ADm, early onset | 163890, 168601, 605543, 127750 |
| UCHL1 | 4p13 | Ubiquitin carboxyl-terminal esterase L1 | PD5, neurodegeneration with optic atrophy | ADm, AR (HZ), juvenile-onset | 191342, 613643, 615491 |
| VPS35 | 16q11.2 | Vacuolar protein sorting 35 | PD17 | ADm, early and late onset | 601501, 614203 |
|
Vascular cognitive impairment | |||||
| ABCC6 | 16p13.11 | ATP-binding cassette, subfamily C, member 6 | Arterial calcification; pseudoxanthoma elasticum; pseudoxanthoma elasticum forme fruste | AR (HZ), infantile onset; AR; ADm | 603234, 614473, 264800, 177850 |
| COL4A1 | 13q34 | Collagen type IV, alpha-1 | Angiopathy, brain small vessel disease, porencephaly 1, intracerebral haemorrhage susceptibility | ADm, infantile onset | 120130, 611773, 607595, 175780, 614519 |
| COL4A2 | 13q34 | Collagen type IV, alpha-2 | Porencephaly 2, intracerebral haemorrhage susceptibility | ADm, infantile onset | 120090, 614483, 614519 |
| HTRA1 | 10q26.13 | HTRA serine peptidase 1 | CARASIL syndrome, macular degeneration | AR (HZ), early onset | 602194, 600142, 610149 |
| NOTCH3 | 19p13.12 | Notch homology protein 3 | Infantile myofibromatosis 2, CADASIL | ADm, early onset | 600276, 615293, 125310 |
| SAMHD1 | 20q11.23 | SAM domain and HD domain 1 | Aicardi-Goutieres syndrome 5, Chilblain lupus 2 | AR (HZ and CH), AD, infantile onset | 606754, 612954, 614415 |
| TREX1 | 3p21.31 | 3-prime repair exonuclease 1 | Aicardi-Goutieres syndrome 1, Chilblain lupus, Vasculopathy, retinal, with cerebral leukodystrophy | AR (HZ and CH), juvenile onset, AD, AD | 606609, 225750, 610448, 192315 |
Abbreviations: ACD, autosomal co-dominant; AD, Alzheimer’s disease; ADm, autosomal dominant; ALS, amyotrophic lateral sclerosis; AR, autosomal recessive; CARASIL syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CH, compound heterozygous; CMT disease, Charcot-Marie-Tooth disease; FTD, frontotemporal dementia; HDLS, leukoencephalopathy, diffuse hereditary, with spheroids; HET4, hereditary essential tremor, 4; HMN7B, neuropathy, distal hereditary motor, type VIIB; HSN1E, hereditary sensory neuropathy type 1E; HZ, homozygous; LBD, Lewy body dementia; NCL, neuronal ceroid-lipofuscinoses; NBIA2A, neurodegeneration with brain iron accumulation 2A; NBIA2B, neurodegeneration with brain iron accumulation 2B; PD, Parkinson’s disease; OMIM, Online Mendelian Inheritance in Man; PMID, PubMed identification; YV syndrome, Yunis–Varon syndrome.
Age of onset was classified as ‘late onset’ if greater than 65 years of age.