Table 3. Downregulated ataxia-related genes in MWK.
Mutation or knockout (KO) of several listed genes are known to cause SCA in humans as well as motor dysfunction and ataxia in mice. The list also includes genes downregulated in P18 MWK mice with exception of Shank2, which is upregulated in P18 MWK. Cell type expression is based on Allen Brain Atlas ISHH images and published papers. CN-cerebellar nuclei, BG-Bergman glia, GC-granule cells, GoC-Golgi cells, PC-Purkinje cells, S/BC-stellate and basket cells. The list shows genes with FDR Adjusted p < 0.003.
| Official Symbol |
Official Full Name (also known as) | Cell type expression |
FDR Adj p Value |
SCA, SCA models and mouse mutants | References |
|---|---|---|---|---|---|
| Fgf7 | fibroblast growth factor 7 | PC | 3.2E-45 | downregulated in P18 MWK | Dulneva et al., 2015 |
| Doc2b | double C2, beta | PC | 6.3E-39 | downregulated in P18 MWK | Dulneva et al., 2015 |
| Shank2 | SH3/ankyrin domain gene 2 | PC, GoC, S/BC, CN | 3.2E-32 | PC-specific KO; downregulated in SCA2 model; upregulated in P18 MWK | Dulneva et al., 2015; Peter et al., 2016; Arsović et al., 2020 |
| Grid2ip | glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein 1 | PC | 5.8E-27 | listed under Gid2 | |
| Stk17b | serine/threonine kinase 17b (apoptosis-inducing) (DRAK2) | PC | 1.2E-24 | downregulated in SCA1, SCA7, SCA14, SCA41 models; and P18 MWK | Dulneva et al., 2015; Wu and Kapfhammer, 2021, 2022 |
| Hipk2 | homeodomain interacting protein kinase 2 | PC | 1.2E-18 | KO mouse | Anzilotti et al., 2015 |
| Camk2a | calcium/calmodulin-dependent protein kinase II alpha | PC | 3.1E-15 | downregulated in SCA2 model | Arsović et al., 2020 |
| Camk1d | calcium/calmodulin-dependent protein kinase ID | no signal | 4.3E-15 | downregulated in SCA2 model | Arsović et al., 2020 |
| Rora | RAR-related orphan receptor alpha | PC, S/BC, CN | 1.5E-14 | staggerer mice; RORA−/− mouse; human mutation | Guissart et al., 2018; Lalonde and Strazielle, 2007, 2019; Halbach et al., 2017 |
| Ptpn4 | protein tyrosine phosphatase, nonreceptor type 4 | PC, GoC, CN | 1.6E-14 | KO mouse | Kina et al., 2007 |
| Grm4 | glutamate receptor, metabotropic 4 (mGluR4) | GC, CN | 3.2E-14 | KO mouse; downregulated in SCA2 model | Pekhletski et al., 1996; Arsović et al., 2020 |
| Frrs1l | ferric-chelate reductase 1 like (6430704M03Rik) | PC | 6.2E-13 | KO mouse | Wang et al., 2022a |
| Dgkh | diacylglycerol kinase, eta | PC | 1.5E-12 | KO mouse; downregulated in SCA2 model and P18 MWK | Dulneva et al., 2015; Hozumi et al., 2017 |
| Bean1 | brain expressed, associated with Nedd4, 1 | PC | 2.2E-12 | SCA31 | Ishikawa and Nagai, 2019; Ishikawa, 2023 |
| Atp2b3 | ATPase, Ca++ transporting, plasma membrane 3 (PMCA3) | PC, GC, S/BC, CN | 2.8E-11 | spontaneous shaker mutant rat; human mutation | Calì et al., 2015; Figueroa et al., 2016; Erekat, 2017 |
| Gabra1 | gamma-aminobutyric acid (GABA) A receptor, subunit alpha 1 | PC, S/BC, CN | 4.1E-10 | KO mouse | Nietz et al., 2020 |
| Far2 | fatty acyl CoA reductase 2 | PC, GoC | 6.4E-10 | downregulated in P18 MWK | Dulneva et al., 2015 |
| Cdc42ep1 | CDC42 effector protein (Rho GTPase binding) 1 | BG | 2.4E-09 | KO mouse | Ageta-Ishihara et al., 2015 |
| Cdkl5 | cyclin-dependent kinase-like 5 | GC, CN | 4.7E-09 | KO mouse | Sivilia et al., 2016 |
| Kcnc3 | potassium voltage gated channel, Shaw-related subfamily, member 3 | PC, CN | 6.9E-09 | SCA13 | Waters, 1993; Duarri et al., 2015 |
| Cbln1 | cerebellin 1 precursor protein | GC, CN | 9.5E-09 | KO mouse | Hirai et al., 2005; Matsuda and Yuzaki, 2012 |
| Caln1 | calneuron 1 | PC, GoC, CN | 1.4E-08 | downregulated in SCA2 model | Arsović et al., 2020 |
| Cacna2d2 | calcium channel, voltage-dependent, alpha 2/delta subunit 2 | PC, GoC, S/BC, CN | 1.7E-08 | Ducky mutation mouse | Barclay et al., 2001; Brodbeck et al., 2002 |
| Ptprr | protein tyrosine phosphatase, receptor | PC | 2.7E-08 | PTPRR−/− mouse | Chirivi et al., 2007; Hendriks et al., 2009 |
| Igfbp5 | insulin-like growth factor binding protein 5 | GC | 8.8E-08 | downregulated in SCA2 model | Arsović et al., 2020 |
| Icmt | isoprenylcysteine carboxyl methyltransferase (PCCMT) | PC | 2.5E-07 | downregulated in SCA1 model and Atxn2 KO mouse | Halbach et al., 2017; Lin et al., 2000 |
| Atp8a2 | ATPase, aminophospholipid transporterlike, class I, type 8 A, member 2 | PC, CN | 8.6E-07 | mutation in humans | Narishige et al., 2022; Onat et al., 2013 |
| Cbln3 | cerebellin 3 precursor protein | GC | 9.6E-07 | downregulated in SCA2 model | Arsović et al., 2020 |
| Car8 | carbonic anhydrase 8 | PC, CN | 2.0E-06 | Waddles mutant mouse | White et al., 2016; Shimobayashi and Kapfhammer, 2018 |
| Sacs | sacsin | PC | 2.3E-06 | Autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) | Engert et al., 2000; Márquez, 2021 |
| Cacna1g | calcium channel, voltage-dependent, T type, alpha 1G subunit (Cav3.1) | PC, GoC | 3.3E-06 | SCA42 | Chemin et al., 2018; Hashiguchi et al., 2019; Berecki et al., 2020 |
| Atp2b2 | ATPase, Ca++ transporting, plasma membrane 2 (PMCA2) | PC, GoC, CN | 4.1E-06 | KO mouse | Empson et al., 2010; Kozel et al., 1998 |
| Itpka | inositol 1,4,5-trisphosphate 3-kinase A | PC | 4.3E-06 | downregulated in SCA2 | Arsović et al., 2020 |
| Scn2a1 | sodium channel, voltage-gated, type II, alpha | GC | 5.4E-06 | mutations | Liao et al., 2010 |
| Slc1a6 | solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6 (EAAT4) | PC | 1.3E-05 | episodic human ataxia, downregulated in SCA1 model, KO mouse, | Lin et al., 2000; Jen et al., 2005; de Vries et al., 2009; Choi et al., 2017; Perkins et al., 2018 |
| Shank1 | SH3/ankyrin domain gene 1 | PC | 1.5E-05 | downregulated in SCA2 model | Arsović et al., 2020 |
| Camk4 | calcium/calmodulin-dependent protein kinase IV | GC | 2.7E-05 | mutation in humans, downregulated in SCA2 model | Zech et al., 2018; Arsović et al., 2020 |
| Cdk5r1 | cyclin-dependent kinase 5, regulatory subunit 1 (p35) | PC | 3.5E-05 | PC specific KO mouse | He et al., 2014 |
| Gpd1 | hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase) | BG | 4.1E-05 | downregulated in Atxn2 KO mouse | Halbach et al., 2017 |
| Scn1a | sodium channel, voltage-gated, type I, alpha (Nav1.1) | PC, GoC | 5.2E-05 | KO mouse; Dravet syndrome | Kalume et al., 2007; Hoffman-Zacharska et al., 2015; Gataullina and Dulac, 2017; Hoxha et al., 2018 |
| Ank1 | ankyrin 1, erythroid | PC, GoC, CN | 2.1E-04 | nb/nb mutation KO mouse, PHARC (polyneuropathy, | Peters et al., 1991 |
| Abhd16a | abhydrolase domain containing 16 A | GC, CN | 2.2E-04 | hearing loss, ataxia, retinitis pigmentosa, and cataract) in human | Singh et al., 2020 |
| Itpr1 | inositol 1,4,5-trisphosphate receptor 1 (IP3R1) | PC | 2.4E-04 | SCA15, SCA16, SCA29, Gillespie syndrome, downregulated in SCA1 and SCA2 models | Halbach et al., 2017; Lin et al., 2000; Romaniello et al., 2022 |
| Scn4b | sodium channel, type IV, beta (Navβ4) | PC, CN | 2.5E-04 | KO mouse | Hoxha et al., 2018; Ransdell et al., 2017 |
| Homer3 | homer scaffolding protein 3 | PC, S/BC, CN | 4.4E-04 | downregulated in SCA2 model | Arsović et al., 2020 |
| Grm3 | glutamate receptor, metabotropic 3 (mGluR3) | GoC | 6.4E-04 | downregulated in SCA2 model | Arsović et al., 2020 |
| Hpcal1 | hippocalcin-like 1 | PC | 6.4E-04 | downregulated in SCA2 model | Arsović et al., 2020 |
| Grid2 | glutamate receptor, ionotropic, delta 2 | PC | 1.2E-03 | SCA18; Lurcher mouse; hotfoot mouse; KO mouse | Lalouette et al., 1998; Doughty et al., 2000; Lalonde and Strazielle, 2007, 2019; Hills et al., 2013; Ceylan et al., 2021 |
| Fgf14 | fibroblast growth factor 14 | GC, CN | 1.6E-03 | SCA27 | Bosch et al., 2015; Shakkottai et al., 2009 |
| Agtpbp1 | ATP/GTP binding protein 1 (Nna1) | PC | 2.1E-03 | Pcd mutant mouse | Lalonde and Strazielle, 2007, 2019; Zhou et al., 2018 |