MCID: SPN293
MIFTS: 48

Spinocerebellar Ataxia 12

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

Aliases & Classifications for Spinocerebellar Ataxia 12

MalaCards integrated aliases for Spinocerebellar Ataxia 12:

Name: Spinocerebellar Ataxia 12 57 53 75 29 13 6 73
Sca12 57 24 53 59 75 55
Spinocerebellar Ataxia Type 12 12 24 53 59 15
Ataxia, Spinocerebellar, Type 12 40

Characteristics:

Orphanet epidemiological data:

59
spinocerebellar ataxia type 12
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

57
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:

32
spinocerebellar ataxia 12:
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance The penetrance is unknown, but as noted some individuals with an expansion may have a very late onset, or potentially may never develop the disease. however, relatively few at-risk individuals without clinical evidence of sca12 have been tested...

Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Spinocerebellar Ataxia 12

NIH Rare Diseases : 53 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 aceruloplasminemia and autosomal dominant cerebellar ataxia, 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 cerebellar atrophy and parkinsonism

UniProtKB/Swiss-Prot : 75 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
GeneReviews: NBK1202

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, Autosomal Recessive 1
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 Type 16
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 25)
# Related Disease Score Top Affiliating Genes
1 aceruloplasminemia 28.3 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A PPP2R2B
2 autosomal dominant cerebellar ataxia 26.9 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 ATXN8OS
3 spinocerebellar ataxia, autosomal recessive 12 11.1
4 spinocerebellar ataxia 18 10.3 ATXN3 ATXN7 CACNA1A
5 spinocerebellar ataxia 6 10.3 ATXN3 ATXN7 CACNA1A
6 spinocerebellar ataxia 8 10.3 ATXN8OS PPP2R2B
7 neuronal intranuclear inclusion disease 10.3 ATXN1 ATXN3
8 spinocerebellar ataxia 31 10.2 ATXN3 ATXN7 CACNA1A
9 spinocerebellar degeneration 10.2 ATXN1 ATXN2 ATXN3
10 spinal and bulbar muscular atrophy, x-linked 1 10.2 ATXN1 ATXN3 ATXN7
11 central nervous system disease 10.0 ATXN3 CACNA1A PRNP
12 nervous system disease 10.0 ATXN3 CACNA1A PRNP
13 spinocerebellar ataxia 2 10.0 ATXN2 ATXN3 ATXN7 CACNA1A
14 cerebellar degeneration 9.9 ATXN2 CACNA1A
15 ataxia-oculomotor apraxia 3 9.9
16 neuronitis 9.9
17 cerebellar disease 9.8 ATXN2 ATXN3 ATXN7 CACNA1A PPP2R2B
18 friedreich ataxia 1 9.6 ATXN1 ATXN2 ATXN3 ATXN8OS CACNA1A
19 parkinson disease, late-onset 9.6 ATXN2 ATXN3 ATXN8OS TBP
20 spinocerebellar ataxia 17 9.5 ATN1 ATXN3 ATXN7 CACNA1A TBP
21 spinocerebellar ataxia 1 9.3 ATN1 ATXN1 ATXN3 ATXN7 ATXN8OS CACNA1A
22 machado-joseph disease 9.2 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A
23 dentatorubral-pallidoluysian atrophy 9.0 ATN1 ATXN2 ATXN3 ATXN7 CACNA1A PPP2R2B
24 huntington disease 8.7 ATN1 ATXN1 ATXN3 CREB1 PRNP TBP
25 hereditary ataxia 8.6 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

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Spinocerebellar Ataxia 12:

59 32 (show all 33)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cerebellar atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0001272
2 parkinsonism 59 32 frequent (33%) Frequent (79-30%) HP:0001300
3 hyperreflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001347
4 cerebral atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0002059
5 action tremor 59 32 Frequent (79-30%) HP:0002345
6 limb dysmetria 59 32 frequent (33%) Frequent (79-30%) HP:0002406
7 tremor by anatomical site 59 32 frequent (33%) Frequent (79-30%) HP:0030188
8 behavioral abnormality 59 32 occasional (7.5%) Occasional (29-5%) HP:0000708
9 dementia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000726
10 bradykinesia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002067
11 intention tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0002080
12 postural tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0002174
13 unsteady gait 59 32 occasional (7.5%) Occasional (29-5%) HP:0002317
14 hypokinesia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002375
15 poor fine motor coordination 59 32 occasional (7.5%) Occasional (29-5%) HP:0007010
16 sensorimotor neuropathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0007141
17 abnormal pyramidal signs 59 32 occasional (7.5%) Occasional (29-5%) HP:0007256
18 ataxia 59 Frequent (79-30%)
19 abnormality of the cerebellum 59 Frequent (79-30%)
20 gait disturbance 59 Occasional (29-5%)
21 cognitive impairment 59 Occasional (29-5%)
22 facial myokymia 32 HP:0000317
23 abnormality of eye movement 32 HP:0000496
24 depressivity 32 HP:0000716
25 anxiety 32 HP:0000739
26 delusions 32 HP:0000746
27 dysarthria 32 HP:0001260
28 dysmetria 32 HP:0001310
29 progressive cerebellar ataxia 32 HP:0002073
30 dysdiadochokinesis 32 HP:0002075
31 cerebral cortical atrophy 32 HP:0002120
32 head tremor 32 HP:0002346
33 axial dystonia 32 HP:0002530

UMLS symptoms related to Spinocerebellar Ataxia 12:


dysdiadochokinesis, head tremor

GenomeRNAi Phenotypes related to Spinocerebellar Ataxia 12 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Apoptosis resistance GR00093-A-0 8.8 PPP2R2B PPP6C PTPA

MGI Mouse Phenotypes related to Spinocerebellar Ataxia 12:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.07 TBP TFAP4 WWOX ATN1 ATXN1 ATXN2
2 behavior/neurological MP:0005386 10.02 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A CREB1
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 9.23 ATN1 ATXN1 ATXN7 CREB1 DNM1L PRNP

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 29 PPP2R2B

Anatomical Context for Spinocerebellar Ataxia 12

MalaCards organs/tissues related to Spinocerebellar Ataxia 12:

41
Eye, Cerebellum, Spinal Cord, Testes

Publications for Spinocerebellar Ataxia 12

Articles related to Spinocerebellar Ataxia 12:

# Title Authors Year
1
Mapping of autosomal dominant cerebellar ataxia without the pathogenic PPP2R2B mutation to the locus for spinocerebellar ataxia 12. ( 20937954 )
2010
2
The spinocerebellar ataxia 12 gene product and protein phosphatase 2A regulatory subunit Bbeta2 antagonizes neuronal survival by promoting mitochondrial fission. ( 18940801 )
2008
3
Molecular and clinical correlation in five Indian families with spinocerebellar ataxia 12. ( 11761478 )
2001

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.27_29CAG(7_28) (p.Ser17_Ser19del) NT expansion Pathogenic rs193922942 GRCh37 Chromosome 5, 146258292: 146258294
2 PPP2R2B NM_181675.3(PPP2R2B): c.27_29CAG(7_28) (p.Ser17_Ser19del) NT expansion Pathogenic rs193922942 GRCh38 Chromosome 5, 146878729: 146878731
3 PPP2R2B NM_181675.3(PPP2R2B): c.55_57delAGC (p.Ser19del) deletion Benign GRCh37 Chromosome 5, 146258291: 146258293
4 PPP2R2B NM_181675.3(PPP2R2B): c.55_57delAGC (p.Ser19del) deletion Benign GRCh38 Chromosome 5, 146878728: 146878730

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 nuclear euchromatin GO:0005719 9.43 CREB1 TBP
3 integral component of mitochondrial outer membrane GO:0031307 9.37 FIS1 TOMM22
4 protein phosphatase type 2A complex GO:0000159 9.32 PPP2R2B PTPA
5 nuclear inclusion body GO:0042405 9.26 ATXN1 ATXN3
6 mitochondrial outer membrane GO:0005741 9.26 DNM1L FIS1 PPP2R2B TOMM22
7 nuclear matrix GO:0016363 8.92 ATN1 ATXN1 ATXN3 ATXN7
8 cytoplasm GO:0005737 10.22 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A

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

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of apoptotic process GO:0043065 9.65 CREB1 DNM1L PTPA TFAP4 TOMM22
2 release of cytochrome c from mitochondria GO:0001836 9.54 DNM1L FIS1
3 mitochondrial fission GO:0000266 9.52 DNM1L FIS1
4 mitochondrion morphogenesis GO:0070584 9.51 DNM1L FIS1
5 calcium-mediated signaling using intracellular calcium source GO:0035584 9.49 FIS1 PRNP
6 regulation of mitochondrion organization GO:0010821 9.48 DNM1L FIS1
7 positive regulation of mitochondrial fission GO:0090141 9.46 DNM1L FIS1
8 peroxisome fission GO:0016559 9.43 DNM1L FIS1
9 mitochondrial fragmentation involved in apoptotic process GO:0043653 9.4 DNM1L FIS1
10 response to amyloid-beta GO:1904645 9.37 CACNA1A PRNP
11 cellular response to lipid GO:0071396 9.32 DNM1L FIS1
12 response to hypobaric hypoxia GO:1990910 9.16 DNM1L FIS1
13 response to flavonoid GO:1905395 8.96 DNM1L FIS1
14 cellular response to thapsigargin GO:1904579 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 9.55 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A

Sources for Spinocerebellar Ataxia 12

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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