SCA12
MCID: SPN293
MIFTS: 51

Spinocerebellar Ataxia 12 (SCA12)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Spinocerebellar Ataxia 12

MalaCards integrated aliases for Spinocerebellar Ataxia 12:

Name: Spinocerebellar Ataxia 12 58 54 76 30 13 6 74
Sca12 58 54 60 76 56
Spinocerebellar Ataxia Type 12 12 54 60 15
Ataxia, Spinocerebellar, Type 12 41

Characteristics:

Orphanet epidemiological data:

60
spinocerebellar ataxia type 12
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
age at onset 8 to 55 years (mean 40 years)
normal cag repeat length is 7 to 32 triplets
pathogenic cag repeat length is 51 to 78 triplets


HPO:

33
spinocerebellar ataxia 12:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Spinocerebellar Ataxia 12

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 98762Disease definitionSpinocerebellar ataxia type 12 (SCA12) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by the presence of action tremor associated with relatively mild cerebellar ataxia. Associated pyramidal and extrapyramidal signs and dementia have been reported.EpidemiologyPrevalence is unknown. Approximately 40 families have been reported.Clinical descriptionThe age of symptomatic onset ranges from 8 to 55 years with most patients presenting in the 4th decade.EtiologyLike SCA8 the pathogenesis of SCA12 seems to be related to a toxic effect at the RNA level as it is caused by a CAG expansion at the 5' end of the PPP2R2B gene on chromosome 5q31-5q32.PrognosisPrognosis is essentially good. In many cases progression of the illness is slow and in general life expectancy is not affected.Visit the Orphanet disease page for more resources.

MalaCards based summary : Spinocerebellar Ataxia 12, also known as sca12, is related to spinocerebellar ataxia 8 and spinocerebellar ataxia 36, and has symptoms including dysdiadochokinesis and head tremor. An important gene associated with Spinocerebellar Ataxia 12 is PPP2R2B (Protein Phosphatase 2 Regulatory Subunit Bbeta), and among its related pathways/superpathways are Akt Signaling and 4-1BB Pathway. Affiliated tissues include eye, cerebellum and spinal cord, and related phenotypes are hyperreflexia and cerebellar atrophy

Disease Ontology : 12 An autosomal dominant cerebellar ataxia that is characterized by minor ataxia and intention tremor, has material basis in CAG expansion of the PPP2R2B gene.

UniProtKB/Swiss-Prot : 76 Spinocerebellar ataxia 12: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA12 is an autosomal dominant cerebellar ataxia (ADCA).

Description from OMIM: 604326

Related Diseases for Spinocerebellar Ataxia 12

Diseases in the Spinocerebellar Ataxia 2 family:

Spinocerebellar Ataxia 31 Spinocerebellar Ataxia 29
Spinocerebellar Ataxia 34 Spinocerebellar Ataxia 1
Spinocerebellar Ataxia 7 Spinocerebellar Ataxia 6
Spinocerebellar Ataxia, Autosomal Recessive 2 Spinocerebellar Ataxia, Autosomal Recessive 3
Spinocerebellar Ataxia 4 Spinocerebellar Ataxia 5
Spinocerebellar Ataxia 10 Spinocerebellar Ataxia 12
Spinocerebellar Ataxia 11 Spinocerebellar Ataxia 13
Spinocerebellar Ataxia 14 Spinocerebellar Ataxia 15
Spinocerebellar Ataxia 17 Spinocerebellar Ataxia, Autosomal Recessive 4
Spinocerebellar Ataxia 19 Spinocerebellar Ataxia 21
Spinocerebellar Ataxia 18 Spinocerebellar Ataxia, Autosomal Recessive 6
Spinocerebellar Ataxia 20 Spinocerebellar Ataxia 25
Spinocerebellar Ataxia 8 Spinocerebellar Ataxia, Autosomal Recessive 7
Spinocerebellar Ataxia 26 Spinocerebellar Ataxia 27
Spinocerebellar Ataxia 23 Spinocerebellar Ataxia 28
Spinocerebellar Ataxia, Autosomal Recessive 8 Spinocerebellar Ataxia 9
Spinocerebellar Ataxia 30 Spinocerebellar Ataxia, Autosomal Recessive 10
Spinocerebellar Ataxia 35 Spinocerebellar Ataxia 32
Spinocerebellar Ataxia 36 Spinocerebellar Ataxia, Autosomal Recessive 11
Spinocerebellar Ataxia, Autosomal Recessive 12 Spinocerebellar Ataxia, Autosomal Recessive 13
Spinocerebellar Ataxia, Autosomal Recessive 14 Spinocerebellar Ataxia, Autosomal Recessive 15
Spinocerebellar Ataxia, Autosomal Recessive 16 Spinocerebellar Ataxia 37
Spinocerebellar Ataxia 38 Spinocerebellar Ataxia 40
Spinocerebellar Ataxia, Autosomal Recessive 17 Spinocerebellar Ataxia, Autosomal Recessive 18
Spinocerebellar Ataxia, Autosomal Recessive 20 Spinocerebellar Ataxia 41
Spinocerebellar Ataxia, Autosomal Recessive 21 Spinocerebellar Ataxia 42
Spinocerebellar Ataxia, Autosomal Recessive 22 Spinocerebellar Ataxia, Autosomal Recessive 23
Spinocerebellar Ataxia 43 Spinocerebellar Ataxia, Autosomal Recessive 24
Spinocerebellar Ataxia, Autosomal Recessive 25 Spinocerebellar Ataxia, Autosomal Recessive 26
Spinocerebellar Ataxia 44 Spinocerebellar Ataxia 45
Spinocerebellar Ataxia 46 Spinocerebellar Ataxia 47
Spinocerebellar Ataxia 48 Spinocerebellar Ataxia, Autosomal Recessive 27
Spinocerebellar Ataxia Type 19/22 Grid2-Related Spinocerebellar Ataxia
Spinocerebellar Ataxia Autosomal Recessive 5

Diseases related to Spinocerebellar Ataxia 12 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 29)
# Related Disease Score Top Affiliating Genes
1 spinocerebellar ataxia 8 30.5 ATXN8OS PPP2R2B
2 spinocerebellar ataxia 36 30.3 ATXN2 PPP2R2B
3 spinocerebellar ataxia 17 29.8 ATN1 ATXN3 ATXN7 CACNA1A TBP
4 aceruloplasminemia 29.4 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A PPP2R2B
5 autosomal dominant cerebellar ataxia 29.3 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 ATXN8OS
6 huntington disease 29.2 ATN1 ATXN1 ATXN3 CREB1 PRNP TBP
7 spinocerebellar ataxia, autosomal recessive 12 11.3
8 spinocerebellar ataxia 10 10.3
9 tremor 10.2
10 spinocerebellar ataxia 18 10.2 ATXN3 ATXN7 CACNA1A
11 spinocerebellar ataxia 6 10.2 ATXN3 ATXN7 CACNA1A
12 spinocerebellar ataxia 31 10.1 ATXN3 ATXN7 CACNA1A
13 spinal and bulbar muscular atrophy, x-linked 1 10.1 ATXN1 ATXN3 ATXN7
14 neuronal intranuclear inclusion disease 10.1 ATXN1 ATXN3
15 cerebellar disease 10.1 ATXN3 ATXN7 CACNA1A PPP2R2B
16 huntington disease-like 1 10.1 PRNP TBP
17 spasmodic dysphonia 10.1
18 spinocerebellar ataxia 2 10.0 ATXN2 ATXN3 ATXN7 CACNA1A
19 nervous system disease 10.0 ATXN3 CACNA1A PRNP
20 fragile x tremor/ataxia syndrome 10.0
21 ataxia and polyneuropathy, adult-onset 10.0
22 primary cerebellar degeneration 10.0 ATXN1 ATXN2 ATXN3 CACNA1A
23 friedreich ataxia 1 10.0 ATXN1 ATXN3 ATXN8OS CACNA1A
24 autosomal genetic disease 10.0 ATXN1 ATXN3 ATXN7 CACNA1A
25 parkinson disease, late-onset 9.9 ATXN2 ATXN3 ATXN8OS TBP
26 spinocerebellar ataxia 1 9.7 ATN1 ATXN1 ATXN3 ATXN7 ATXN8OS CACNA1A
27 machado-joseph disease 9.7 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A
28 dentatorubral-pallidoluysian atrophy 9.6 ATN1 ATXN2 ATXN3 ATXN7 CACNA1A PPP2R2B
29 hereditary ataxia 9.4 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A

Graphical network of the top 20 diseases related to Spinocerebellar Ataxia 12:



Diseases related to Spinocerebellar Ataxia 12

Symptoms & Phenotypes for Spinocerebellar Ataxia 12

Human phenotypes related to Spinocerebellar Ataxia 12:

60 33 (show all 33)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperreflexia 60 33 frequent (33%) Frequent (79-30%) HP:0001347
2 cerebellar atrophy 60 33 frequent (33%) Frequent (79-30%) HP:0001272
3 cerebral atrophy 60 33 frequent (33%) Frequent (79-30%) HP:0002059
4 parkinsonism 60 33 frequent (33%) Frequent (79-30%) HP:0001300
5 limb dysmetria 60 33 frequent (33%) Frequent (79-30%) HP:0002406
6 tremor by anatomical site 60 33 frequent (33%) Frequent (79-30%) HP:0030188
7 abnormal pyramidal sign 60 33 occasional (7.5%) Occasional (29-5%) HP:0007256
8 behavioral abnormality 60 33 occasional (7.5%) Occasional (29-5%) HP:0000708
9 intention tremor 60 33 occasional (7.5%) Occasional (29-5%) HP:0002080
10 poor fine motor coordination 60 33 occasional (7.5%) Occasional (29-5%) HP:0007010
11 dementia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000726
12 postural tremor 60 33 occasional (7.5%) Occasional (29-5%) HP:0002174
13 bradykinesia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002067
14 hypokinesia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002375
15 sensorimotor neuropathy 60 33 occasional (7.5%) Occasional (29-5%) HP:0007141
16 unsteady gait 60 33 occasional (7.5%) Occasional (29-5%) HP:0002317
17 action tremor 60 33 Frequent (79-30%) HP:0002345
18 abnormality of eye movement 33 HP:0000496
19 depressivity 33 HP:0000716
20 ataxia 60 Frequent (79-30%)
21 dysarthria 33 HP:0001260
22 gait disturbance 60 Occasional (29-5%)
23 cognitive impairment 60 Occasional (29-5%)
24 anxiety 33 HP:0000739
25 dysmetria 33 HP:0001310
26 cerebral cortical atrophy 33 HP:0002120
27 dysdiadochokinesis 33 HP:0002075
28 progressive cerebellar ataxia 33 HP:0002073
29 abnormality of the cerebellum 60 Frequent (79-30%)
30 head tremor 33 HP:0002346
31 delusions 33 HP:0000746
32 axial dystonia 33 HP:0002530
33 facial myokymia 33 HP:0000317

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
dysarthria
hyperreflexia
dysmetria
dementia
dysdiadochokinesis
more
Head And Neck Face:
facial myokymia

Neurologic Peripheral Nervous System:
subclinical sensory or sensorimotor neuropathy

Neurologic Behavioral Psychiatric Manifestations:
anxiety
delusions
depression

Head And Neck Eyes:
ocular movement abnormalities

Clinical features from OMIM:

604326

UMLS symptoms related to Spinocerebellar Ataxia 12:


dysdiadochokinesis, head tremor

MGI Mouse Phenotypes related to Spinocerebellar Ataxia 12:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.07 ATN1 ATXN1 ATXN2 ATXN3 CACNA1A CREB1
2 behavior/neurological MP:0005386 10.02 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A
3 mortality/aging MP:0010768 9.97 ATN1 ATXN1 ATXN2 ATXN7 CACNA1A CREB1
4 nervous system MP:0003631 9.7 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A
5 skeleton MP:0005390 9.17 ATXN1 ATXN7 CREB1 DNM1L PRNP TBP

Drugs & Therapeutics for Spinocerebellar Ataxia 12

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Spinocerebellar Ataxia 12

Genetic Tests for Spinocerebellar Ataxia 12

Genetic tests related to Spinocerebellar Ataxia 12:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia 12 30 PPP2R2B

Anatomical Context for Spinocerebellar Ataxia 12

MalaCards organs/tissues related to Spinocerebellar Ataxia 12:

42
Eye, Cerebellum, Spinal Cord, Skin, Liver

Publications for Spinocerebellar Ataxia 12

Articles related to Spinocerebellar Ataxia 12:

(show all 22)
# Title Authors Year
1
Frequency of SCA8, SCA10, SCA12, SCA36, FXTAS and C9orf72 repeat expansions in SCA patients negative for the most common SCA subtypes. ( 29316893 )
2018
2
Exploration of CAG triplet repeat in nontranslated region of SCA12 gene. ( 27350687 )
2016
3
Analysis of SCA8, SCA10, SCA12, SCA17 and SCA19 in patients with unknown spinocerebellar ataxia: a Thai multicentre study. ( 26374734 )
2015
4
Identification of 46 CAG repeats within PPP2R2B as probably the shortest pathogenic allele for SCA12. ( 25634432 )
2015
5
Mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of spinocerebellar ataxia type 12 (SCA12). ( 21471219 )
2011
6
Mapping of autosomal dominant cerebellar ataxia without the pathogenic PPP2R2B mutation to the locus for spinocerebellar ataxia 12. ( 20937954 )
2010
7
The CAG repeat in SCA12 functions as a cis element to up-regulate PPP2R2B expression. ( 20533062 )
2010
8
EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias. ( 20050888 )
2010
9
Utilizing linkage disequilibrium information from Indian Genome Variation Database for mapping mutations: SCA12 case study. ( 19417544 )
2009
10
The spinocerebellar ataxia 12 gene product and protein phosphatase 2A regulatory subunit Bbeta2 antagonizes neuronal survival by promoting mitochondrial fission. ( 18940801 )
2008
11
Evidence of a common founder for SCA12 in the Indian population. ( 16138911 )
2005
12
Detection of large pathogenic expansions in FRDA1, SCA10, and SCA12 genes using a simple fluorescent repeat-primed PCR assay. ( 15096564 )
2004
13
Polymorphism of trinucleotide repeats in non-translated regions of SCA8 and SCA12 genes: allele distribution in a Polish control group. ( 14960773 )
2004
14
Coincidence of a large SCA12 repeat allele with a case of Creutzfeld-Jacob disease. ( 15146023 )
2004
15
Why is SCA12 different from other SCAs? ( 14526180 )
2003
16
Analysis of SCA8 and SCA12 loci in 134 Italian ataxic patients negative for SCA1-3, 6 and 7 CAG expansions. ( 12140678 )
2002
17
SCA12 is a rare locus for autosomal dominant cerebellar ataxia: a study of an Indian family. ( 11198281 )
2001
18
Molecular and clinical correlation in five Indian families with spinocerebellar ataxia 12. ( 11761478 )
2001
19
The SCA12 mutation as a rare cause of spinocerebellar ataxia. ( 11708992 )
2001
20
SCA12: an unusual mutation leads to an unusual spinocerebellar ataxia. ( 11719278 )
2001
21
Expansion of a novel CAG trinucleotide repeat in the 5' region of PPP2R2B is associated with SCA12. ( 10581021 )
1999
22
Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? ( 9403486 )
1997

Variations for Spinocerebellar Ataxia 12

ClinVar genetic disease variations for Spinocerebellar Ataxia 12:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PPP2R2B NM_181675.3(PPP2R2B): c.27CAG[(7_28)[ (p.Ser10[(7-28)]) NT expansion Benign rs10591869 GRCh37 Chromosome 5, 146258292: 146258294
2 PPP2R2B NM_181675.3(PPP2R2B): c.27CAG[(7_28)[ (p.Ser10[(7-28)]) NT expansion Benign rs10591869 GRCh38 Chromosome 5, 146878729: 146878731
3 PPP2R2B NM_181675.3(PPP2R2B): c.55_57delAGC (p.Ser19del) deletion Benign rs10591869 GRCh37 Chromosome 5, 146258291: 146258293
4 PPP2R2B NM_181675.3(PPP2R2B): c.55_57delAGC (p.Ser19del) deletion Benign rs10591869 GRCh38 Chromosome 5, 146878728: 146878730
5 PPP2R2B NM_181678.2(PPP2R2B): c.86C> T (p.Ala29Val) single nucleotide variant Uncertain significance rs1554126530 GRCh38 Chromosome 5, 146701094: 146701094
6 PPP2R2B NM_181678.2(PPP2R2B): c.86C> T (p.Ala29Val) single nucleotide variant Uncertain significance rs1554126530 GRCh37 Chromosome 5, 146080657: 146080657

Expression for Spinocerebellar Ataxia 12

Search GEO for disease gene expression data for Spinocerebellar Ataxia 12.

Pathways for Spinocerebellar Ataxia 12

GO Terms for Spinocerebellar Ataxia 12

Cellular components related to Spinocerebellar Ataxia 12 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.76 CREB1 DNM1L FIS1 PPP2R2B PPP6C TFAP4
2 mitochondrial outer membrane GO:0005741 9.56 DNM1L FIS1 PPP2R2B TOMM22
3 nuclear inclusion body GO:0042405 9.37 ATXN1 ATXN3
4 nuclear matrix GO:0016363 9.26 ATN1 ATXN1 ATXN3 ATXN7
5 protein phosphatase type 2A complex GO:0000159 8.8 PPP2R2B PPP2R5B PTPA
6 cytoplasm GO:0005737 10.13 ATN1 ATXN1 ATXN2 ATXN3 CACNA1A DNM1L

Biological processes related to Spinocerebellar Ataxia 12 according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of apoptotic process GO:0043065 9.65 CREB1 DNM1L PTPA TFAP4 TOMM22
2 calcium-mediated signaling using intracellular calcium source GO:0035584 9.56 FIS1 PRNP
3 mitochondrion morphogenesis GO:0070584 9.55 DNM1L FIS1
4 release of cytochrome c from mitochondria GO:0001836 9.54 DNM1L FIS1
5 regulation of phosphoprotein phosphatase activity GO:0043666 9.54 PPP2R2B PPP2R5B PTPA
6 mitochondrial fission GO:0000266 9.52 DNM1L FIS1
7 regulation of peptidyl-tyrosine phosphorylation GO:0050730 9.51 PPP2R5B PRNP
8 regulation of mitochondrion organization GO:0010821 9.49 DNM1L FIS1
9 positive regulation of mitochondrial fission GO:0090141 9.48 DNM1L FIS1
10 mitochondrial fragmentation involved in apoptotic process GO:0043653 9.46 DNM1L FIS1
11 peroxisome fission GO:0016559 9.43 DNM1L FIS1
12 response to amyloid-beta GO:1904645 9.4 CACNA1A PRNP
13 response to hypobaric hypoxia GO:1990910 9.32 DNM1L FIS1
14 cellular response to lipid GO:0071396 9.16 DNM1L FIS1
15 cellular response to thapsigargin GO:1904579 8.96 DNM1L FIS1
16 response to flavonoid GO:1905395 8.62 DNM1L FIS1

Molecular functions related to Spinocerebellar Ataxia 12 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.58 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A
2 protein phosphatase regulator activity GO:0019888 9.13 PPP2R2B PPP2R5B PTPA

Sources for Spinocerebellar Ataxia 12

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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