SCAR23
MCID: SPN377
MIFTS: 36

Spinocerebellar Ataxia, Autosomal Recessive 23 (SCAR23)

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

Aliases & Classifications for Spinocerebellar Ataxia, Autosomal Recessive 23

MalaCards integrated aliases for Spinocerebellar Ataxia, Autosomal Recessive 23:

Name: Spinocerebellar Ataxia, Autosomal Recessive 23 57 29 6
Scar23 57 12 58 72
Autosomal Recessive Cerebellar Ataxia-Epilepsy-Intellectual Disability Syndrome Due to Tud Deficiency 12 58
Autosomal Recessive Spinocerebellar Ataxia 23 12 15
Ataxia, Spinocerebellar, Autosomal Recessive, Type 23 39
Spinocerebellar Ataxia Autosomal Recessive Type 23 58
Spinocerebellar Ataxia, Autosomal Recessive, 23 72

Characteristics:

Orphanet epidemiological data:

58
autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to tud deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
some patients may become wheelchair-bound
onset of seizures in childhood (range infancy to 12 years)
seizures may remit in childhood but then recur


HPO:

31
spinocerebellar ataxia, autosomal recessive 23:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Spinocerebellar Ataxia, Autosomal Recessive 23

UniProtKB/Swiss-Prot : 72 Spinocerebellar ataxia, autosomal recessive, 23: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR23 patients manifest epilepsy, intellectual disability, and gait ataxia.

MalaCards based summary : Spinocerebellar Ataxia, Autosomal Recessive 23, also known as scar23, is related to autosomal dominant cerebellar ataxia and ataxia and polyneuropathy, adult-onset. An important gene associated with Spinocerebellar Ataxia, Autosomal Recessive 23 is TDP2 (Tyrosyl-DNA Phosphodiesterase 2), and among its related pathways/superpathways is DNA Damage. Affiliated tissues include eye, liver and cerebellum, and related phenotypes are intellectual disability and abnormal facial shape

Disease Ontology : 12 An autosomal recessive cerebellar ataxia characterized by epilepsy, intellectual disability, and gait ataxia that has material basis in homozygous or compound heterozygous mutation in TDP2 on chromosome 6p22.3.

OMIM® : 57 Autosomal recessive spinocerebellar ataxia-23 is a neurologic disorder characterized by epilepsy, intellectual disability, and gait ataxia (summary by Gomez-Herreros et al., 2014). (616949) (Updated 20-May-2021)

Related Diseases for Spinocerebellar Ataxia, Autosomal Recessive 23

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, Autosomal Recessive 28 Spinocerebellar Ataxia Type 19/22
Grid2-Related Spinocerebellar Ataxia Spinocerebellar Ataxia Autosomal Recessive 5

Diseases related to Spinocerebellar Ataxia, Autosomal Recessive 23 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 autosomal dominant cerebellar ataxia 29.7 TDP1 PNKP PDYN
2 ataxia and polyneuropathy, adult-onset 10.4
3 spinocerebellar ataxia 23 10.2
4 alacrima, achalasia, and mental retardation syndrome 10.2
5 epilepsy 9.9
6 ruijs-aalfs syndrome 9.9 TDP2 TDP1
7 ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia 9.8 TDP1 PNKP
8 lig4 syndrome 9.7 TDP1 PNKP
9 cerebellar disease 9.6 TDP1 PNKP
10 spinocerebellar ataxia type 1 with axonal neuropathy 9.3 TOP2A TDP2 TDP1 PNKP
11 hereditary ataxia 9.2 TDP2 TDP1 PNKP PDYN

Graphical network of the top 20 diseases related to Spinocerebellar Ataxia, Autosomal Recessive 23:



Diseases related to Spinocerebellar Ataxia, Autosomal Recessive 23

Symptoms & Phenotypes for Spinocerebellar Ataxia, Autosomal Recessive 23

Human phenotypes related to Spinocerebellar Ataxia, Autosomal Recessive 23:

58 31 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 abnormal facial shape 58 31 hallmark (90%) Very frequent (99-80%) HP:0001999
3 seizure 31 hallmark (90%) HP:0001250
4 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
5 brachycephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000248
6 generalized hypotonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001290
7 seizures 58 Very frequent (99-80%)
8 microcephaly 31 HP:0000252
9 easy fatigability 31 HP:0003388
10 arrhythmia 31 HP:0011675
11 hyponatremia 31 HP:0002902
12 neutropenia 31 HP:0001875
13 hypersomnia 31 HP:0100786

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
intellectual disability
cerebellar ataxia
hypotonia
seizures, refractory
normal early development

Muscle Soft Tissue:
easy fatigability
decreased complex i/iii and ii/iii activity seen on muscle biopsy

Hematology:
neutropenia

Cardiovascular Heart:
cardiac arrhythmia

Abdomen Gastrointestinal:
gastric dysmotility

Head And Neck Head:
microcephaly

Laboratory Abnormalities:
hyponatremia
high lactate/pyruvate ratio

Neurologic Behavioral Psychiatric Manifestations:
hypersomnia

Head And Neck Face:
dysmorphic facial features, nonspecific

Clinical features from OMIM®:

616949 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Spinocerebellar Ataxia, Autosomal Recessive 23 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.17 TDP1 TOP2A
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.17 TDP1 TOP2A
3 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-3 9.17 PNKP TDP1 TDP2

Drugs & Therapeutics for Spinocerebellar Ataxia, Autosomal Recessive 23

Search Clinical Trials , NIH Clinical Center for Spinocerebellar Ataxia, Autosomal Recessive 23

Genetic Tests for Spinocerebellar Ataxia, Autosomal Recessive 23

Genetic tests related to Spinocerebellar Ataxia, Autosomal Recessive 23:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia, Autosomal Recessive 23 29 TDP2

Anatomical Context for Spinocerebellar Ataxia, Autosomal Recessive 23

MalaCards organs/tissues related to Spinocerebellar Ataxia, Autosomal Recessive 23:

40
Eye, Liver, Cerebellum, Spinal Cord

Publications for Spinocerebellar Ataxia, Autosomal Recessive 23

Articles related to Spinocerebellar Ataxia, Autosomal Recessive 23:

# Title Authors PMID Year
1
Confirming TDP2 mutation in spinocerebellar ataxia autosomal recessive 23 (SCAR23). 6 57 61
30109272 2018
2
TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function. 57 6
24658003 2014
3
Characterization of a novel loss-of-function variant in TDP2 in two adult patients with spinocerebellar ataxia autosomal recessive 23 (SCAR23). 61
32651480 2020
4
Consolidating the Role of TDP2 Mutations in Recessive Spinocerebellar Ataxia Associated with Pediatric Onset Drug Resistant Epilepsy and Intellectual Disability (SCAR23). 61
31410782 2019
5
Erratum: Confirming TDP2 mutation in spinocerebellar ataxia autosomal recessive 23 (SCAR23). 61
30588497 2018

Variations for Spinocerebellar Ataxia, Autosomal Recessive 23

ClinVar genetic disease variations for Spinocerebellar Ataxia, Autosomal Recessive 23:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TDP2 NM_016614.3(TDP2):c.425+1G>A SNV Pathogenic 226424 rs372245668 GRCh37: 6:24658788-24658788
GRCh38: 6:24658560-24658560
2 TDP2 NM_016614.3(TDP2):c.413_414delinsAA (p.Ser138Ter) Indel Pathogenic 226425 rs879255601 GRCh37: 6:24658800-24658801
GRCh38: 6:24658572-24658573
3 TDP2 NM_016614.3(TDP2):c.949C>T (p.Arg317Ter) SNV Pathogenic 1033833 GRCh37: 6:24651156-24651156
GRCh38: 6:24650928-24650928
4 TDP2 NM_016614.3(TDP2):c.97G>T (p.Ala33Ser) SNV Uncertain significance 1030570 GRCh37: 6:24666994-24666994
GRCh38: 6:24666766-24666766

Expression for Spinocerebellar Ataxia, Autosomal Recessive 23

Search GEO for disease gene expression data for Spinocerebellar Ataxia, Autosomal Recessive 23.

Pathways for Spinocerebellar Ataxia, Autosomal Recessive 23

Pathways related to Spinocerebellar Ataxia, Autosomal Recessive 23 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.27 TOP2A TDP1 PNKP

GO Terms for Spinocerebellar Ataxia, Autosomal Recessive 23

Biological processes related to Spinocerebellar Ataxia, Autosomal Recessive 23 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA repair GO:0006281 9.33 TDP2 TDP1 PNKP
2 double-strand break repair GO:0006302 9.26 TDP2 TDP1
3 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.13 TDP2 TDP1 PNKP
4 cellular response to DNA damage stimulus GO:0006974 8.92 TOP2A TDP2 TDP1 PNKP

Molecular functions related to Spinocerebellar Ataxia, Autosomal Recessive 23 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 double-stranded DNA binding GO:0003690 9.16 TDP1 PNKP
2 nuclease activity GO:0004518 8.96 TDP2 TDP1
3 single-stranded DNA binding GO:0003697 8.62 TDP2 TDP1

Sources for Spinocerebellar Ataxia, Autosomal Recessive 23

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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