Details of Disease

General Information of Disease (ID: DISH7224)

• Disease Name: Spinocerebellar ataxia type 6
• Synonyms: spinocerebellar ataxia 6; SCA6; spinocerebellar ataxia type 6; autosomal dominant cerebellar ataxia type III caused by mutation in CACNA1A; CACNA1A autosomal dominant cerebellar ataxia type III
• Definition: Spinocerebellar ataxia type 6 (SCA6) is the most common subtype of autosomal dominant cerebellar ataxia type III (ADCA type III) characterized by late-onset and slowly progressive gait ataxia and other cerebellar signs such as impaired muscle coordination and nystagmus.
• Disease Hierarchy:
  DISQNP59: CACNA1A-related complex neurodevelopmental disorder
  DISQBYEM: Autosomal dominant cerebellar ataxia type III
  DISH7224: Spinocerebellar ataxia type 6
• Disease Identifiers:
  MONDO ID: MONDO_0008457
  MESH ID: D020754
  UMLS CUI: C0752124
  OMIM ID: 183086
  MedGen ID: 148458
  Orphanet ID: 98758
  SNOMED CT ID: 715752006

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ATXN3	TT6A17J	Limited	Biomarker	[1]
CACNA1F	TTJ0SO4	Limited	Genetic Variation	[2]
FOXC1	TTNT3YA	Limited	Biomarker	[3]
ATXN2	TTPQJ7P	Strong	Genetic Variation	[4]
PRKCG	TTRFOXJ	Strong	Biomarker	[5]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
CACNA1A	DTYKGPB	Strong	Autosomal dominant	[6]

This Disease Is Related to 16 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CALB1	OTM7IXDG	Limited	Biomarker	[7]
CIC	OTFXCHNZ	Limited	Biomarker	[8]
GFI1	OT9HB9H8	Limited	Biomarker	[9]
MPI	OTBH6ZK1	Limited	Biomarker	[10]
PPP2R2B	OTSFVC82	Limited	Biomarker	[11]
RBM17	OT9ROJCL	Limited	Biomarker	[8]
TTBK2	OT90YSM5	Limited	Biomarker	[12]
AFG3L2	OTRPMAUX	Strong	Biomarker	[13]
ATXN1	OTQF0HNR	Strong	Biomarker	[8]
ATXN7	OTL3YF1H	Strong	Biomarker	[14]
BEAN1	OT0WLH27	Strong	Genetic Variation	[15]
CACNA1A	OTY08SIX	Strong	Autosomal dominant	[6]
LY6E	OTMG16BZ	Strong	Genetic Variation	[4]
PDYN	OTEJ6430	Strong	Genetic Variation	[16]
TK2	OTS1V4XB	Strong	Genetic Variation	[15]
ATXN1L	OTYIHGTD	Definitive	Therapeutic	[17]

References

• [1] Tremor in the Degenerative Cerebellum: Towards the Understanding of Brain Circuitry for Tremor.Cerebellum. 2019 Jun;18(3):519-526. doi: 10.1007/s12311-019-01016-6.
• [2] Calcium channels and channelopathies of the central nervous system.Mol Neurobiol. 2002 Feb;25(1):31-50. doi: 10.1385/MN:25:1:031.
• [3] 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.
• [4] Genetic analysis of ten common degenerative hereditary ataxia loci in patients with essential tremor.Parkinsonism Relat Disord. 2015 Aug;21(8):943-7. doi: 10.1016/j.parkreldis.2015.06.004. Epub 2015 Jun 6.
• [5] 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.
• [6] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [7] Morphological Purkinje cell changes in spinocerebellar ataxia type 6.Acta Neuropathol. 2000 Oct;100(4):371-6. doi: 10.1007/s004010000201.
• [8] 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.
• [9] 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.
• [10] Alternative splicing in the C-terminal tail of Cav2.1 is essential for preventing a neurological disease in mice.Hum Mol Genet. 2017 Aug 15;26(16):3094-3104. doi: 10.1093/hmg/ddx193.
• [11] Trinucleotide repeat disorders.Handb Clin Neurol. 2017;145:383-391. doi: 10.1016/B978-0-12-802395-2.00027-4.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Impaired Adaptive Motor Learning Is Correlated With Cerebellar Hemispheric Gray Matter Atrophy in Spinocerebellar Ataxia Patients: A Voxel-Based Morphometry Study.Front Neurol. 2019 Nov 14;10:1183. doi: 10.3389/fneur.2019.01183. eCollection 2019.
• [16] The effect of 3,4-diaminopyridine on the patients with hereditary pure cerebellar ataxia.J Neurol Sci. 2010 May 15;292(1-2):81-4. doi: 10.1016/j.jns.2010.01.021. Epub 2010 Feb 23.
• [17] Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes. Nat Genet. 2007 Mar;39(3):373-9. doi: 10.1038/ng1977. Epub 2007 Feb 18.