Table 3.
Yeast-prion-like genes genetically linked to neurological diseases in humansa
| Ensembl gene ID | Name | NQP ?b | Prion prediction ?b | Neurodegenerative ?c | Diseases linked to gene (with OMIM numbers) |
|---|---|---|---|---|---|
| Nucleic-acid binding/Transcription factor (PC00171, PC00218) | |||||
| ENSG00000104973 | MED25, Mediator complex subunit 25 | X | -- | U | Charcot-Marie-Tooth disease, type 2B2, #605589 |
| ENSG00000112592 | TBP, TATA box binding protein | X | X | U | Spinocerebellar ataxia 17, #607136 |
| ENSG00000204842 | ATXN2, Ataxin 2 | X | -- | U | Amyotrophic lateral sclerosis, susceptibility to, 13, #183090; |
| Parkinson disease, late-onset, susceptibility to, #168600; | |||||
| Spinocerebellar ataxia 2, #183090 | |||||
| ENSG00000085224 | ATRX, Alpha thalassemia/mental retardtn. syndrome X-linked | X | X | -- | Mental retardation-hypotonic facies syndrome, X-linked, #309580 |
| ENSG00000089280 | FUS RNA binding protein | X | X | U | Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia, #608030; |
| Tremor, hereditary essential, 4, #614782 | |||||
| ENSG00000100888 | CHD8, Chromodomain helicase DNA binding protein 8 | X | -- | -- | Autism, susceptibility to, 18, #615032 |
| ENSG00000160299 | PCNT, Pericentrin | X | -- | -- | Microcephalic osteodysplastic primordial dwarfism, type II, #210720 |
| ENSG00000182944 | EWSR1, EWS RNA-binding protein 1 | X | X | -- | Neuroepithelioma, #612219 |
| ENSG00000111752 | PHC1, Polyhomeotic homolog 1 | X | X | -- | Microcephaly 11, primary, autosomal recessive, #615414 |
| ENSG00000198026 | ZNF335, Zinc finger protein 335 | X | -- | -- | Microcephaly, #615095 |
| ENSG00000052850 | ALX4, ALX homeobox 4 | + | -- | -- | Craniosynostosis 5, #615529 |
| ENSG00000066427 | ATXN3, Ataxin 3 | X | -- | U | Machado-Joseph disease, #109150 |
| ENSG00000140521 | POLG, Polymerase (DNA directed), © | X | -- | U | Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), #607459 |
| ENSG00000156876 | SASS6, SAS-6 centriolar assembly protein | + | -- | -- | Microcephaly 14, primary, autosomal recessive, #616402 |
| ENSG00000169083 | AR, Androgen receptor | X | -- | U | Spinal and bulbar muscular atrophy of Kennedy, #313200 |
| Cytoskeletal protein (PC00085) | |||||
| ENSG00000066279 | ASPM, abnormal spindle microtubule assembly | X | X | -- | Microcephaly 5, #608716 |
| ENSG00000131018 | SYNE1, Spectrin repeat containing nuclear envelope 1 | X | -- | U | Emery-Dreifuss muscular dystrophy 4, autosomal dominant, #612998; |
| Spinocerebellar ataxia, autosomal recessive 8, #610743 | |||||
| ENSG00000151914 | DST, Dystonin | X | -- | -- | Neuropathy, hereditary sensory and autonomic, type VI, #614653 |
| ENSG00000008056 | SYN1, synapsin I | X | -- | -- | X-linked epilepsy, #300491 |
| ENSG00000133454 | MYO18B, Myosin XVIIIB | X | -- | -- | Klippel-Feil syndrome 4, autosomal recessive, with myopathy, #616549 |
| ENSG00000166813 | KIF7, Kinesin family member 7 | X | -- | -- | Joubert syndrome, etc., #200990 |
| ENSG00000178209 | PLEC, Plectin | X | -- | CM | various muscular dystrophy, #226670, #613723 |
| ENSG00000277586 | NEFL, Neurofilament light polypeptide | -- | X | U | Charcot-Marie-Tooth disease, #607734, #607684 |
| ENSG00000054654 | SYNE2, Spectrin repeat containing, nuclear envelope 2 | + | -- | CM | Emery-Dreifuss muscular dystrophy 5, #612999 |
| ENSG00000100345 | MYH9, Myosin, heavy chain 9, non-muscle | + | -- | -- | Macrothrombocytopenia and progressive sensorineural deafness, #600208 |
| ENSG00000138778 | CENPE, Centromere protein E, 312 kDa | + | -- | -- | Microcephaly 13, primary, autosomal recessive, #616051 |
| ENSG00000198947 | DMD, Dystrophin | + | -- | CM | Becker muscular dystrophy, #300376; Duchenne muscular dystrophy, #310200 |
| Transporter (PC00227) | |||||
| ENSG00000157388 | CACNA1D, Ca channel, voltage-depdt., L type, 〈 1D subunit | -- | X | -- | Primary aldosteronism, #615474 |
| Sinoatrial node dysfunction and deafness, #614896 | |||||
| ENSG00000198734 | F5, Coagulation factor V (proaccelerin, labile factor) | -- | X | -- | Suscept. to stroke, #601367 |
| ENSG00000007314 | SCN4A, Na channel, voltage gated, type IV 〈 subunit | -- | X | -- | Hyperkalemic periodic paralysis, type 2, #170500, #613345; |
| Myotonia congenita, atypical, acetazolamide-responsive, #608390; Paramyotonia congenita, #168300 | |||||
| ENSG00000036828 | CASR, Calcium-sensing receptor | X | -- | -- | Idiopathic generalized epilepsy, #612899 |
| ENSG00000141837 | CACNA1A, Ca channel, voltage-depdt., P/Q type, 〈 1A subunit | X | -- | U | Spinocerebellar ataxia 6, #183086; |
| Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, #141500; | |||||
| Episodic ataxia, type 2, #108500; | |||||
| ENSG00000164588 | HCN1, Hyperpolariztn. activated cyclic-nucleotide-gated K channel 1 | X | -- | -- | Epileptic encephalopathy, early infantile, 24, #615871 |
| Others | |||||
| ENSG00000116001 | TIA1, TIA1 cytotoxic granule-associated RNA binding protein | + | X | CM | Welander distal myopathy, #604454 |
| ENSG00000157212 | PAXIP1, PAX interacting protein 1 | X | X | CN | Alzheimer disease, susceptibility to, #104300 |
| ENSG00000162928 | PEX13, Peroxisomal biogenesis factor 13 | -- | X | -- | Peroxisome biogenesis disorder 11A (Zellweger), #614883 |
| ENSG00000197386 | HTT, Huntingtin | X | X | U | Huntington disease, #143100 |
| ENSG00000204120 | GIGYF2, GRB10 interacting GYF protein 2 | X | -- | U | Parkinson disease 11, #607688 |
| ENSG00000103995 | CEP152, Centrosomal protein 152 kDa | X | -- | -- | Microcephaly 9, primary, autosomal recessive, #614852 |
| ENSG00000114354 | TFG, TRK-fused gene | X | X | U | Hereditary motor and sensory neuropathy, Okinawa type, #604484; |
| Spastic paraplegia 57, autosomal recessive, #615658 | |||||
| ENSG00000120948 | TARDBP, TAR DNA binding protein | -- | X | U | Amyotrophic lateral sclerosis 10, with or without FTD, #612069; |
| Frontotemporal lobar degeneration, TARDBP-related, #612069 | |||||
| ENSG00000122566 | HNRNPA2B1, Heterogen. nuclear ribonucleoprotein A2B1d | -- | X | CNd | Inclusion body myopathy with early-onset Paget disease, #615422 |
| ENSG00000135486 | HNRNPA1, Heterogeneous nuclear ribonucleoprotein A1d | -- | X | Ud | Amyotrophic lateral sclerosis 20, #615426; |
| Inclusion body myopathy wtih early-onset Paget disease without frontotemporal dementia 3, #615424 | |||||
| ENSG00000136352 | NKX2-1, NK2 homeobox 1 | X | -- | -- | Chorea, hereditary benign, #118700; |
| Choreoathetosis, hypothyroidism, and neonatal respiratory distress, #610978 | |||||
| ENSG00000145868 | FBXO38, F-box protein 38 | X | -- | U | Neuronopathy, distal hereditary motor, type IID, #615575 |
| ENSG00000152795 | HNRNPDL, Heterogeneous nuclear ribonucleoprotein D-like | -- | X | CM | Limb-girdle muscular dystrophy, type 1G, #609115 |
| ENSG00000154118 | JPH3, Junctophilin 3 | -- | X | CN | Huntington disease-like 2, #606438 |
| ENSG00000168000 | BSCL2, Berardinelli-Seip congenital lipodystrophy 2 (seipin) | -- | X | U | Encephalopathy, progressive, with or without lipodystrophy, #615924; |
| Neuropathy, distal hereditary motor, type VA, #600794; | |||||
| Silver spastic paraplegia syndrome, #270685 | |||||
| ENSG00000186472 | PCLO, Piccolo presynaptic cytomatrix protein | X | -- | U | Pontocerebellar hypoplasia, type 3, #608027 |
| ENSG00000269335 | IKBKG, Inhibitor of | light polypeptide B-cell gene enhancer, kinase © | X | -- | -- | Incontinentia pigmenti, #308300 |
| ENSG00000027075 | PRKCH, Protein kinase C, eta | -- | X | -- | Cerebral infarction, susceptibility to, #601367 |
| ENSG00000060237 | WNK1, WNK lysine deficient protein kinase 1 | X | X | U | Neuropathy, hereditary sensory and autonomic, type II, #201300 |
| ENSG00000074047 | GLI2, GLI family zinc finger 2 | + | -- | -- | Holoprosencephaly-9, #610829 |
| ENSG00000111676 | ATN1, Atrophin 1 | X | X | U | Dentatorubro-pallidoluysian atrophy, #125370 |
| ENSG00000124788 | ATXN1, Ataxin 1 | X | X | U | Spinocerebellar ataxia 1, #164400 |
| ENSG00000127838 | PNKD, Paroxysmal nonkinesigenic dyskinesia | -- | X | -- | Paroxysmal nonkinesigenic dyskinesia, #118800 |
| ENSG00000148356 | LRSAM1, Leucine rich repeat and sterile motif containing 1 | X | -- | U | Charcot-Marie-Tooth disease, axonal, type 2P, #614436 |
| ENSG00000163635 | ATXN7, Ataxin7 | X | -- | U | Spinocerebellar ataxia 7, #164500 |
| ENSG00000164342 | TLR3, Toll-like receptor 3 | + | -- | -- | Herpes simplex encephalitis, susceptibility to, 2 #613002 |
| ENSG00000188021 | UBQLN2, Ubiquilin 2 | + | -- | U | Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia, #300857 |
aThe genes are grouped according to the three most common PANTHER protein classes [48]. In making these listings, the four organisms with very high rates of yeast-prion-like proteins (see Table 1) are not considered
bNQPs are N/Q-rich proteins as defined. In the ‘NQP?’ column, genes which encode an NQP with LPS P-value <1e-10 are labelled with an ‘X’ , those with P-value otherwise <1e-08 are labelled with a ‘+’ sign. If the gene has an algorithmic prion prediction, it is labelled with an ‘X’ in the ‘Prion Prediction?’ column
cGenes that are in the UniProt neurodegenerative list are labelled ‘U’. To other labels arise from curation of the scientific literature: those that were determined as neurodegeneration-linked genes are labelled ‘CN’ , whereas those that are specifically linked to muscular degeneration are labelled ‘CM’
dThese two were identified as linked to neurodegenerative illnesses after a biased screen for proteins with prion-like domains. However, they have previously identified links to neurological illnesses. Removal of these two cases found in such screens (hnRNPA2B1 and hnRNPA1, which are linked to ALS and other muscular degeneration [25]) does not affect the calculations. Also, these two genes have previously discovered genetic linkages to neurodegenerative disorders [50, 51]