Details of Disease

Disease Name

Spinocerebellar ataxia type 1

OPCA1; olivopontocerebellar atrophy 4; OPCA4; OPCA 1; cerebelloparenchymal disorder 1; OPCA 4; olivopontocerebellar atrophy 1; Menzel type OPCA; Schut-haymaker type OPCA; spinocerebellar atrophy 1; spinocerebellar ataxia 1; autosomal dominant cerebellar ataxia type I caused by mutation in ATXN1; spinocerebellar ataxia type 1; ATXN1 autosomal dominant cerebellar ataxia type I; Sca1

Definition

Spinocerebellar ataxia type 1 (SCA1) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I) characterized by dysarthria, writing difficulties, limb ataxia, and commonly nystagmus and saccadic abnormalities.

Disease Hierarchy

DIS947AF: Autosomal dominant cerebellar ataxia type I

DIS6BW88: Huntington disease-like syndrome

DISF7BO2: Spinocerebellar ataxia type 1

Disease Identifiers

MONDO ID

MONDO_0008119

MESH ID

D020754

UMLS CUI

C0752120

OMIM ID

164400

MedGen ID

155703

Orphanet ID

98755

SNOMED CT ID

715748006

General Information of Disease (ID: DISF7BO2)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
FOXC1	TTNT3YA	Limited	Biomarker	[1]
GRM1	TTVBPDM	Limited	Biomarker	[2]
GLO1	TTV9A7R	moderate	Biomarker	[3]
ATXN2	TTPQJ7P	Strong	Biomarker	[4]
ATXN3	TT6A17J	Strong	Altered Expression	[5]
CACNA1A	TTX4QDJ	Strong	Biomarker	[6]
PRKCG	TTRFOXJ	Strong	Biomarker	[7]
RPS6KA5	TTYXEPL	Definitive	Altered Expression	[8]
UBE3A	TTUZX6V	Definitive	Biomarker	[9]
------------------------------------------------------------------------------------


⏷ Show the Full List of 9 DTT(s)

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
FXN	DEXVHDB	moderate	Biomarker	[10]
------------------------------------------------------------------------------------

This Disease Is Related to 24 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATXN1L	OTYIHGTD	Limited	Biomarker	[11]
CIC	OTFXCHNZ	Limited	Biomarker	[12]
GFI1	OT9HB9H8	Limited	Biomarker	[13]
LY6E	OTMG16BZ	Limited	Biomarker	[4]
PPP2R2B	OTSFVC82	Limited	Biomarker	[14]
TTBK2	OT90YSM5	Disputed	Biomarker	[15]
PQBP1	OTXCBEAH	moderate	Biomarker	[16]
AFG3L2	OTRPMAUX	Strong	Biomarker	[17]
ANP32A	OTRHPFO2	Strong	Biomarker	[18]
ATXN1	OTQF0HNR	Strong	Autosomal dominant	[19]
ATXN7	OTL3YF1H	Strong	Biomarker	[20]
PDYN	OTEJ6430	Strong	Genetic Variation	[21]
RBM17	OT9ROJCL	Strong	Biomarker	[12]
ATOX1	OT05LF59	Definitive	Genetic Variation	[22]
COIL	OTP4I4DL	Definitive	Biomarker	[23]
HSD17B6	OTSB55D2	Definitive	Biomarker	[24]
IVL	OT4VPNGY	Definitive	Genetic Variation	[25]
NLK	OT2LETFS	Definitive	Biomarker	[26]
PCP2	OT3LUE9M	Definitive	Genetic Variation	[27]
PMPCA	OT5X1G9Q	Definitive	Genetic Variation	[28]
PUM1	OTTMWP8L	Definitive	Biomarker	[29]
RPA1	OT76POLP	Definitive	Biomarker	[30]
SNRNP70	OTP52YZ3	Definitive	Genetic Variation	[31]
TCTE1	OTWL4LDO	Definitive	Genetic Variation	[32]
------------------------------------------------------------------------------------


⏷ Show the Full List of 24 DOT(s)

References

1	FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation.Nat Genet. 2009 Sep;41(9):1037-42. doi: 10.1038/ng.422. Epub 2009 Aug 9.
2	Progressive impairment of cerebellar mGluR signalling and its therapeutic potential for cerebellar ataxia in spinocerebellar ataxia type 1 model mice.J Physiol. 2017 Jan 1;595(1):141-164. doi: 10.1113/JP272950. Epub 2016 Sep 15.
3	Spinocerebellar ataxia (SCA1) in two large Italian kindreds: evidence in favour of a locus position distal to GLO1 and the HLA cluster.Ann Hum Genet. 1991 Jan;55(1):7-15. doi: 10.1111/j.1469-1809.1991.tb00393.x.
4	Protein kinase C activity is a protective modifier of Purkinje neuron degeneration in cerebellar ataxia.Hum Mol Genet. 2018 Apr 15;27(8):1396-1410. doi: 10.1093/hmg/ddy050.
5	Targeting several CAG expansion diseases by a single antisense oligonucleotide.PLoS One. 2011;6(9):e24308. doi: 10.1371/journal.pone.0024308. Epub 2011 Sep 1.
6	The P/Q-type voltage-dependent calcium channel as pharmacological target in spinocerebellar ataxia type 6: gabapentin and pregabalin may be of therapeutic benefit.Med Hypotheses. 2007;68(1):131-6. doi: 10.1016/j.mehy.2006.06.014. Epub 2006 Aug 8.
7	Mutant protein kinase C gamma that causes spinocerebellar ataxia type 14 (SCA14) is selectively degraded by autophagy. Genes Cells. 2010 May;15(5):425-38. doi: 10.1111/j.1365-2443.2010.01395.x. Epub 2010 Apr 11.
8	RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1.Nature. 2013 Jun 20;498(7454):325-331. doi: 10.1038/nature12204. Epub 2013 May 29.
9	Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice.Neuron. 1999 Dec;24(4):879-92. doi: 10.1016/s0896-6273(00)81035-1.
10	Spinocerebellar ataxia: patient and health professional perspectives on whether and how patents affect access to clinical genetic testing.Genet Med. 2010 Apr;12(4 Suppl):S83-S110. doi: 10.1097/GIM.0b013e3181d67e44.
11	RNAi or overexpression: alternative therapies for Spinocerebellar Ataxia Type 1.Neurobiol Dis. 2013 Aug;56:6-13. doi: 10.1016/j.nbd.2013.04.003. Epub 2013 Apr 10.
12	Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1.Nature. 2008 Apr 10;452(7188):713-8. doi: 10.1038/nature06731. Epub 2008 Mar 12.
13	The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins.Cell. 2005 Aug 26;122(4):633-44. doi: 10.1016/j.cell.2005.06.012.
14	The spinocerebellar ataxia 12 gene product and protein phosphatase 2A regulatory subunit Bbeta2 antagonizes neuronal survival by promoting mitochondrial fission.J Biol Chem. 2008 Dec 26;283(52):36241-8. doi: 10.1074/jbc.M800989200. Epub 2008 Oct 21.
15	Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nat Genet. 2007 Dec;39(12):1434-6. doi: 10.1038/ng.2007.43. Epub 2007 Nov 25.
16	PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype.Hum Mol Genet. 2003 Apr 1;12(7):711-25. doi: 10.1093/hmg/ddg084.
17	Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28. Nat Genet. 2010 Apr;42(4):313-21. doi: 10.1038/ng.544. Epub 2010 Mar 7.
18	A novel function of Ataxin-1 in the modulation of PP2A activity is dysregulated in the spinocerebellar ataxia type 1.Hum Mol Genet. 2013 Sep 1;22(17):3425-37. doi: 10.1093/hmg/ddt197. Epub 2013 Apr 29.
19	SCA1 molecular genetics: a history of a 13 year collaboration against glutamines. Hum Mol Genet. 2001 Oct 1;10(20):2307-11. doi: 10.1093/hmg/10.20.2307.
20	Clinical and molecular effect on offspring of a marriage of consanguineous spinocerebellar ataxia type 7 mutation carriers: a family case report.Int J Clin Exp Med. 2014 Dec 15;7(12):5896-903. eCollection 2014.
21	Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3.J Neurol. 1999 Sep;246(9):789-97. doi: 10.1007/s004150050456.
22	Spinocerebellar ataxia type 1.Handb Clin Neurol. 2012;103:399-421. doi: 10.1016/B978-0-444-51892-7.00025-5.
23	p80 coilin, a coiled body-specific protein, interacts with ataxin-1, the SCA1 gene product.Biochim Biophys Acta. 2003 May 20;1638(1):35-42. doi: 10.1016/s0925-4439(03)00038-3.
24	Short-term succinic acid treatment mitigates cerebellar mitochondrial OXPHOS dysfunction, neurodegeneration and ataxia in a Purkinje-specific spinocerebellar ataxia type 1 (SCA1) mouse model.PLoS One. 2017 Dec 6;12(12):e0188425. doi: 10.1371/journal.pone.0188425. eCollection 2017.
25	Peptides containing glutamine repeats as substrates for transglutaminase-catalyzed cross-linking: relevance to diseases of the nervous system.Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14580-5. doi: 10.1073/pnas.93.25.14580.
26	Polyglutamine disease toxicity is regulated by Nemo-like kinase in spinocerebellar ataxia type 1.J Neurosci. 2013 May 29;33(22):9328-36. doi: 10.1523/JNEUROSCI.3465-12.2013.
27	Reduction of protein kinase A-mediated phosphorylation of ATXN1-S776 in Purkinje cells delays onset of Ataxia in a SCA1 mouse model.Neurobiol Dis. 2018 Aug;116:93-105. doi: 10.1016/j.nbd.2018.05.002. Epub 2018 May 11.
28	Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3.Brain. 1996 Oct;119 ( Pt 5):1497-505. doi: 10.1093/brain/119.5.1497.
29	Pumilio1 haploinsufficiency leads to SCA1-like neurodegeneration by increasing wild-type Ataxin1 levels.Cell. 2015 Mar 12;160(6):1087-98. doi: 10.1016/j.cell.2015.02.012.
30	Systems biology analysis of Drosophila in vivo screen data elucidates core networks for DNA damage repair in SCA1.Hum Mol Genet. 2014 Mar 1;23(5):1345-64. doi: 10.1093/hmg/ddt524. Epub 2013 Oct 31.
31	Insights into the mutational history and prevalence of SCA1 in the Indian population through anchored polymorphisms.Hum Genet. 2005 Oct;118(1):107-14. doi: 10.1007/s00439-005-0018-8. Epub 2005 Oct 28.
32	The gene for autosomal dominant spinocerebellar ataxia (SCA1) maps telomeric to the HLA complex and is closely linked to the D6S89 locus in three large kindreds.Am J Hum Genet. 1991 Jul;49(1):23-30.