Table 1.
Major characteristics of genes with pathological repeat expansions and proteins they encode.
| Repeat Location | Gene | Disease a | Repeat Sequence | WT Length | Pathogenic Length b | % Disorder c | References | |
|---|---|---|---|---|---|---|---|---|
| Poly-alanine | Exon | HOXD13 | SPD II | GCG | 15 | >21 | 33.82 | [64,65,66] |
| Exon | HOXA13 | HFGS | GCG | 12 | >17 | 34.28 | [67] | |
| Exon | RUNX2 | CCD | GCG | 17 | >26 | 62.96 | [65,68] | |
| Exon | ZIC2 | HPE | GCG | 9 | -- | 54.89 | [69,70] | |
| Exon | PHOX2B | CCHS | GCG | 20 | -- | 54.15 | [71,72,73] | |
| Exon-X chrom. | SOX3 | XLMR + GHD | GCG | 15 | >25 | 51.12 | [74,75] | |
| Exon-X chrom. | ARX | XLMR | GCG | 16 | >17, >22 | 59.07 | [76,77] | |
| Exon | FOXL2 | BPEIS | GCG | 14 | >21, >24 | 47.34 | [78,79] | |
| Exon | PABPN1 | OPMD | GCG | 10 | >11, >16 | 59.80 | [80,81] | |
| Poly-glutamine | Exon | KCNN3 | Schizo. d | CAG | -- | -- | 37.50 | [82] |
| Exon | JPH3 | HDL2 | CAG/CTG | 6 to 28 | >41 | 51.07 | [83,84,85] | |
| Exon | HTT | HD | CAG | 6 to 35 | >35 | 19.10 | [86,87] | |
| Exon | ATN1 | DRPLA | CAG | 3 to 36 | >48 | 86.05 | [88,89] | |
| Exon | AR | SBMA | CAG | 9 to 36 | >37 | 54.13 | [90] | |
| Exon | ATXN1 | SCA1 | CAG | 6 to 39 | >39 | 54.97 | [91] | |
| Exon | ATXN2 | SCA2 | CAG | 14 to 32 | >33 | 79.13 | [92,93] | |
| Exon | ATXN3 | SCA3 | CAG | 12 to 40 | >54 | 42.03 | [82,94] | |
| Exon | CACNA1A | SCA6 | CAG | 4 to 18 | >20 | 42.08 | [95,96] | |
| Exon | ATXN7 | SCA7 | CAG | 7 to 17 | >33 | 71.30 | [97,98] | |
| Exon | TBP | SCA17 | CAG | 25 to 42 | >44 | 46.31 | [99,100] | |
| Non-coding | 5′ UTR | PPP2R2B | SCA12 | CAG | 7 to 32 | >54 | 7.67 | [101,102] |
| 5′ UTR-X chrom. | FMR1 | FXMR, FXTAS | CGG | 6 to 55 | >200, >55 | 38.29 | [103] | |
| 5′ UTR | DIP2B | FRA12A MR | CGG | 6 to 23 | >200 | 19.73 | [104] | |
| 5′ UTR-X chrom. | FMR2 | FRAXE MR | GCC | -- | >200 | 58.12 | [105,106,107] | |
| 5′ UTR | C9orf72 | C9ALS/FTD | GGGGCC | -- | Unknown | 2.70 | [108,109] | |
| Intron | FXN | FRDA | GAA | 7 to 22 | >66 | 40.00 | [110,111] | |
| Intron | CNBP/zfn9 | DM2 | CCTG | <27 | >75 | 19.77 | [112,113] | |
| Intron | ATXN10 | SCA10 | ATTCT | 10 to 29 | >279 | 5.26 | [114,115] | |
| Intron | NOP56 | SCA36 | GGCCTG | 3 to 8 | >1500 | 26.26 | [116] | |
| Intron | TCF4 | FECD | CTG | -- | >50 | 88.01 | [117,118] | |
| 3′ UTR | DMPK | DM1 | CTG | 5 to 37 | >50 | 14.63 | [119,120] | |
| 3′ UTR | ATXN8OS | SCA8 e | CTG | 6 to 37 | >74 | 68.00 f | [121,122,123] | |
| Exon | ATXN8 | SCA8 e | CAG | 15 to 50 | 71 to 1300 | 100.00 f | [124] | |
| Promoter | CSTB | EPM1 | CCCCGCCCCGCG | 2 to 3 | >14 | 40.82 | [125,126] |
a SPD II, synpolydactyly; HFGS, hand-foot genital syndrome; CCD, cleidocranial dysplasia; HPE, holoprosencephaly cephalic disorder; CCHS, congenital central hypoventilation syndrome; XLMR + GHD, X-linked mental retardation with isolated growth hormone deficiency; XLMR, ARX-nonsyndromic X-linked mental retardation; BPEIS, blepharophimosis, ptosis, and epicanthus inversus syndrome; OPMD, oculopharyngeal muscular dystrophy; Schizo., schizophrenia; HDL2, huntinton’s disease-like 2; HD, Huntington’s disease; DRPLA, dentatorubral-pallidoluysian; SBMA, spinal and bulbar muscular atrophy; SCA, spinocerebellar ataxia; FXMR, fragile X mental retardation; FTXAS, fragile X-associated tremor/ataxia syndrome; FRA12A MR, fragile X mental retardation; FRAXE MR, fragile X mental retardation; ALS, amyotrophic lateral sclerosis; FTD, frontotemporal dementia; FRDA, Friedreich ataxia; DM, myotonic dystrophy; FECD, fuchs endothelial corneal dystrophy; EPM1, myoclonus epilepsy of Unverricht-Lundborg type, WT and pathogenic length refer to number of sequence repeats. b Pathogenic length indicates the threshold of the repeat length, above which the protein-carrier will cause development of pathology. c MobiDB-based predicted consensus disorder content is shown for query proteins (http://mobid.bio.unipd.it/) [127,128]. d Although CAG repeat tract length in KCNN3 was correlated with schizophrenia, this is not a pathological repeat expansion and a cause of disease. e SCA8 is caused by the bidirectional transcription at the SCA8 locus containing ATXN8OS and ATXN8 genes and therefore considered as the ′CTG*CAG′ repeat expansion disease, referring to the complementary base pairs of the ATXN8OS and ATXN8 genes. f For ATXN8OS and ataxin-8 proteins, disorder content was calculated as an averaged value of the overall percent of residues predicted to be disordered by PONDR® VLXT, PONDR® VL3 and PONDR® VSL2.