Details of Disease

General Information of Disease (ID: DISPBCM3)

• Disease Name: Cerebellar degeneration
• Synonyms: cerebral degeneration; neurodegenerative disease of cerebellum; cerebellar degeneration; Brain degeneration; cerebellum neurodegenerative disease; cerebellar Degeneration
• Definition: Degeneration of the cerebellum. It may be an inherited condition, a paraneoplastic syndrome, or secondary to autoimmune disorders.
• Disease Hierarchy:
  DIS2O7WM: Cerebellar disorder
  DISM20FF: Neurodegenerative disease
  DISPBCM3: Cerebellar degeneration
• Disease Identifiers:
  MONDO ID: MONDO_0022687
  UMLS CUI: C0262404
  MedGen ID: 75496
  SNOMED CT ID: 95646004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GABRA3	TT37EDJ	Limited	Biomarker	[1]
UBA1	TTXHWA7	Limited	Biomarker	[1]
ATXN3	TT6A17J	Strong	Biomarker	[2]
CACNA1A	TTX4QDJ	Strong	Genetic Variation	[3]
GRM1	TTVBPDM	Strong	Biomarker	[4]
PNPLA6	TTWAQU2	Strong	Genetic Variation	[5]
TDP1	TT64IHJ	Strong	Biomarker	[6]
PNKP	TTHR3IE	Definitive	Biomarker	[7]

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
AKR1C4	DEAJN47	Strong	Genetic Variation	[8]
TGM6	DEUWCVD	Definitive	Genetic Variation	[9]

This Disease Is Related to 17 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AGTPBP1	OTR92JFR	Strong	Genetic Variation	[10]
ATXN1	OTQF0HNR	Strong	Biomarker	[11]
CDR2	OTD3ZJST	Strong	Biomarker	[12]
DAB1	OTPL9MA3	Strong	Genetic Variation	[13]
MRE11	OTGU8TZM	Strong	Genetic Variation	[14]
RUNX1T1	OT30DED5	Strong	Genetic Variation	[8]
SHQ1	OTFBXX2H	Strong	Genetic Variation	[15]
AAAS	OTJT9T23	Definitive	Biomarker	[16]
ALKBH7	OTJVS8CF	Definitive	Biomarker	[17]
AP2B1	OTL6LZJ4	Definitive	Biomarker	[18]
CDR2L	OT5UVB1J	Definitive	Biomarker	[12]
CNTN4	OTULXVE0	Definitive	Biomarker	[19]
CTNNBL1	OT6KLHPA	Definitive	Biomarker	[18]
NPC2	OTE9UEJC	Definitive	Biomarker	[20]
SAR1A	OTSSRVGV	Definitive	Biomarker	[21]
SLC2A4RG	OTW3LX8D	Definitive	Biomarker	[22]
SPTBN2	OTDMJ75N	Definitive	Genetic Variation	[23]

References

• [1] Mutation screening in Rett syndrome patients.J Med Genet. 2000 Apr;37(4):250-5. doi: 10.1136/jmg.37.4.250.
• [2] Gene-Related Cerebellar Neurodegeneration in SCA3/MJD: A Case-Controlled Imaging-Genetic Study.Front Neurol. 2019 Sep 24;10:1025. doi: 10.3389/fneur.2019.01025. eCollection 2019.
• [3] Cerebellar Degeneration Increases Visual Influence on Dynamic Estimates of Verticality.Curr Biol. 2018 Nov 19;28(22):3589-3598.e3. doi: 10.1016/j.cub.2018.09.049. Epub 2018 Nov 1.
• [4] Glutamate Receptor Antibodies in Autoimmune Central Nervous System Disease: Basic Mechanisms, Clinical Features, and Antibody Detection.Methods Mol Biol. 2019;1941:225-255. doi: 10.1007/978-1-4939-9077-1_15.
• [5] A novel PNPLA6 compound heterozygous mutation identified in a Chinese patient with BoucherNeuhuser syndrome.Mol Med Rep. 2018 Jul;18(1):261-267. doi: 10.3892/mmr.2018.8955. Epub 2018 May 3.
• [6] Studying TDP1 Function in DNA Repair.Methods Mol Biol. 2018;1703:173-181. doi: 10.1007/978-1-4939-7459-7_13.
• [7] Progressive cerebellar atrophy and polyneuropathy: expanding the spectrum of PNKP mutations.Neurogenetics. 2013 Feb;14(1):43-51. doi: 10.1007/s10048-012-0351-8. Epub 2012 Dec 9.
• [8] A post-transcriptional regulatory mechanism restricts expression of the paraneoplastic cerebellar degeneration antigen cdr2 to immune privileged tissues.J Neurosci. 1997 Feb 15;17(4):1406-15. doi: 10.1523/JNEUROSCI.17-04-01406.1997.
• [9] Mutations in TGM6 induce the unfolded protein response in SCA35.Hum Mol Genet. 2017 Oct 1;26(19):3749-3762. doi: 10.1093/hmg/ddx259.
• [10] Biallelic variants in AGTPBP1, involved in tubulin deglutamylation, are associated with cerebellar degeneration and motor neuropathy. Eur J Hum Genet. 2019 Sep;27(9):1419-1426. doi: 10.1038/s41431-019-0400-y. Epub 2019 Apr 11.
• [11] Clinical analysis of adult-onset spinocerebellar ataxias in Thailand.BMC Neurol. 2014 Apr 5;14:75. doi: 10.1186/1471-2377-14-75.
• [12] Paraneoplastic cerebellar degeneration: Yo antibody alters mitochondrial calcium buffering capacity.Neuropathol Appl Neurobiol. 2019 Feb;45(2):141-156. doi: 10.1111/nan.12492. Epub 2018 May 24.
• [13] A Pentanucleotide ATTTC Repeat Insertion in the Non-coding Region of DAB1, Mapping to SCA37, Causes Spinocerebellar Ataxia. Am J Hum Genet. 2017 Jul 6;101(1):87-103. doi: 10.1016/j.ajhg.2017.06.007.
• [14] Disease-associated MRE11 mutants impact ATM/ATR DNA damage signaling by distinct mechanisms.Hum Mol Genet. 2013 Dec 20;22(25):5146-59. doi: 10.1093/hmg/ddt368. Epub 2013 Aug 2.
• [15] Inherited SHQ1 mutations impair interaction with NAP57/dyskerin, a major target in dyskeratosis congenita. Mol Genet Genomic Med. 2017 Nov;5(6):805-808. doi: 10.1002/mgg3.314. Epub 2017 Aug 15.
• [16] Genetic interaction between the m-AAA protease isoenzymes reveals novel roles in cerebellar degeneration.Hum Mol Genet. 2009 Jun 1;18(11):2001-13. doi: 10.1093/hmg/ddp124. Epub 2009 Mar 16.
• [17] ALKBH7 drives a tissue and sex-specific necrotic cell death response following alkylation-induced damage.Cell Death Dis. 2017 Jul 20;8(7):e2947. doi: 10.1038/cddis.2017.343.
• [18] ATM binds to beta-adaptin in cytoplasmic vesicles.Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10146-51. doi: 10.1073/pnas.95.17.10146.
• [19] The contactin 4 gene locus at 3p26 is a candidate gene of SCA16.Neurology. 2006 Oct 10;67(7):1236-41. doi: 10.1212/01.wnl.0000238510.84932.82.
• [20] A novel mouse model of a patient mucolipidosis II mutation recapitulates disease pathology.J Biol Chem. 2014 Sep 26;289(39):26709-26721. doi: 10.1074/jbc.M114.586156. Epub 2014 Aug 8.
• [21] Extensive cerebellar and thalamic degeneration in spinocerebellar ataxia type 10.Parkinsonism Relat Disord. 2019 Sep;66:182-188. doi: 10.1016/j.parkreldis.2019.08.011. Epub 2019 Aug 19.
• [22] An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5' untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains.Am J Hum Genet. 2005 Aug;77(2):280-96. doi: 10.1086/432518. Epub 2005 Jul 6.
• [23] Mutant -III spectrin causes mGluR1 mislocalization and functional deficits in a mouse model of spinocerebellar ataxia type 5.J Neurosci. 2014 Jul 23;34(30):9891-904. doi: 10.1523/JNEUROSCI.0876-14.2014.