Table 2.
Description of human paralogs of genes involved in polyQ SCAs reviewed in this study
| Disease | Paralog | Chromosome location | Origin | RNA expression | Phenotype | Function | References |
|---|---|---|---|---|---|---|---|
| SCA1 | ATXN1L | 16q22.2 | DNA-based duplication | Mainly expressed in brain (higher in gonads and lymphoid tissue)** | Development (brain, lung) | Transcription regulator (CIC-ATXN1 complex) | Tsai et al. (2004); Mizutani et al. (2005); Lam et al. (2006); Carlson et al. (2009); Tong et al. (2011); Vauti et al. (2021) |
| SCA2 | ATXN2L | 16p11.2 | DNA-based duplication | Widely expressed at higher levels in testis | Unknown | Stress grabule assembly (mRNA metabolism) | Meunier et al. (2002); Figueroa and Pulst (2003); Kaehler et al. (2012, 2015); Lee et al. (2018) |
| MJD/ SCA3 | ATXN3L | Xp22.2 | Retrotransposition | Only detected in testis | Unknown (related to cell proliferation/ migration) | Protein deubiquitinase | Rodrigues et al. (2007); Schmitt et al. (2007); Buus et al. (2009); Weeks et al. (2011); Ge et al. (2015); Sousa e Silva et al. (2023) |
| ATXN3L2 | 8q23.2 | Retrotransposition (interrupted ORF) | Unknown | Unknown | Unknown (possibly a processed pseudogene/mRNA) | – | |
| SCA6 | CACNA1B | 9q34 | DNA-based duplication | Mainly detected in brain, pituitary gland, and testis | Development (brain) | High voltage-gated calcium channel | Westenbroek et al. (1992; Wheeler et al. (1994); Catterall et al. (2005); Nakagawasai et al. (2010); Heyes et al. (2015); Gorman et al. (2019) |
| CACNA1E | 1q25.3 | DNA-based duplication | Mainly detected in brain | Unknown (related to synaptic plasticity) | High Voltage-gated calcium channel | Day et al. (1996); Ophoff et al. (1996); Dietrich et al. (2003); Catterall et al. (2005); Parajuli et al. (2012); Heyes et al. (2015) | |
| SCA7 | ATXN7L1 | 7q22.3 | DNA-based duplication | Widely expressed at higher levels in testis | Unknown | Protein binding (SAGA DUBm) | Vermeulen et al. (2010); Helmlinger and Tora (2017) |
| ATXN7L2 | 1p13.3 | DNA-based duplication | Widely expressed at higher levels in skeletal muscle (brain, pituitary gland, and testis)* | Unknown | Unknown (possibly similar to ATXN7L1) | Vermeulen et al. (2010); Helmlinger and Tora (2017) | |
| ATXN7L3 | 17q21.31 | DNA-based duplication | Widely expressed at higher levels in brain | Unknown | Transcription regulator/protein binding (SAGA complex) | Helmlinger et al. (2004); Bonnet et al. (2010); Lang et al. (2011) | |
| ATXN7L3B | 12q21.1 | Retrotransposition | Widely expressed at higher levels in brain and lymphoid tissue (female gonads)* | Unknown | Transcription regulator (transcription factor, lncRNA) | Tan et al. (2014); Li et al. (2016b) | |
| SCA17 | TBPL1 | 6q23.2 | DNA-based duplication | Widely expressed at higher levels in testis | Spermatogenesis | Transcription initiation factor (TATA-less genes) | Moore et al. (1999); Ohbayashi et al. (1999b, a); Rabenstein et al. (1999); Martianov et al. (2001); Zhang et al. (2001); Isogai et al. (2007); Duttke et al. (2014); Kedmi et al. (2014); Wang et al. (2014) |
| TBPL2 | 14q22.3 | DNA-based duplication | Mainly detected in brain and skeletal muscle (testis)** | Oogenesis, muscle differentiation | Transcription initiation factor (TATA-box promoters) | Müller et al. (2001); Persengiev et al. (2003); Bártfai et al. (2004); Jallow et al. (2004); Gazdag et al. (2007, 2009); Akhtar and Veenstra (2009); Malecova et al. (2016) | |
| DRPLA | RERE | 1p36.23 | DNA-based duplication | Widely expressed at higher levels in brain and muscle tissue (female gonads)* | Development (cerebellum) | Transcription factor (histone deacetylases recruitment) | Onodera et al. (1995); Yanagisawa et al. (2000); Waerner et al. (2001); Asai et al. (2006); Wang et al. (2006, 2008); Plaster et al. (2007); Shen et al. (2007); Shen and Peterson (2009) |
ORF, open reading frame
In case gene expression data reported in the literature is only partially supported* or discordant** with databases, the respective additional or alternative tissues are in parentheses. GTEx (http://gtexportal.org/home/); The Human Protein Atlas (http://www.proteinatlas.org/); FANTOM (http://fantom.gsc.riken.jp/)