SCA21
MCID: SPN096
MIFTS: 40

Spinocerebellar Ataxia 21 (SCA21)

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 21

MalaCards integrated aliases for Spinocerebellar Ataxia 21:

Name: Spinocerebellar Ataxia 21 56 52 73 13 71
Spinocerebellar Ataxia Type 21 12 52 58 29 6 15
Sca21 56 52 58 73
Spinocerebellar Ataxia 21 with Mental Retardation and Severe Cognitive Impairment 73
Ataxia, Spinocerebellar, Type 21 39

Characteristics:

Orphanet epidemiological data:

58
spinocerebellar ataxia type 21
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
variable age of onset (range 1 to 30 years)


HPO:

31
spinocerebellar ataxia 21:
Inheritance autosomal dominant inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0050972
OMIM 56 607454
OMIM Phenotypic Series 56 PS164400
MeSH 43 D020754
MESH via Orphanet 44 C537200
ICD10 via Orphanet 33 G11.1
UMLS via Orphanet 72 C1843891
Orphanet 58 ORPHA98773
MedGen 41 C1843891
UMLS 71 C1843891

Summaries for Spinocerebellar Ataxia 21

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 98773 Definition Spinocerebellar ataxia type 21 (SCA21) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive cerebellar ataxia, mild cognitive impairment, postural and/or resting tremor, bradykinesia, and rigidity. Epidemiology Prevalence is unknown. Fewer than 20 cases in a 4-generation French family have been reported to date. Clinical description Mean age of onset is 17.4 years and is relatively early compared to most type I ADCAs. Individuals in successive generations tend to have earlier ages of onset. Parkinsonism was not responsive to L-dopa and magnetic resonance imaging (MRI) revealed cerebellar and brainstem atrophy. Etiology SCA21 maps to chromosome 7p21.3-p15.1 but the gene and gene mutation have not been identified. Prognosis There is insufficient clinical data to draw conclusions concerning prognosis. Visit the Orphanet disease page for more resources.

MalaCards based summary : Spinocerebellar Ataxia 21, also known as spinocerebellar ataxia type 21, is related to spinocerebellar ataxia, autosomal recessive 21 and hereditary ataxia, and has symptoms including tremor, abnormality of extrapyramidal motor function and gait ataxia. An important gene associated with Spinocerebellar Ataxia 21 is TMEM240 (Transmembrane Protein 240), and among its related pathways/superpathways is Spinocerebellar ataxia. Affiliated tissues include eye, cerebellum and spinal cord, and related phenotypes are abnormality of extrapyramidal motor function and gait ataxia

Disease Ontology : 12 An autosomal dominant cerebellar ataxia that is characterized by progressive cerebellar ataxia, cognitive impairment, tremor, bradykinesia and rigidity.

OMIM : 56 Spinocerebellar ataxia-21 (SCA21) is an autosomal dominant neurologic disorder characterized by onset in the first decades of life of slowly progressive cerebellar ataxia, which is associated with cognitive impairment in most patients (summary by Delplanque et al., 2014). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400). (607454)

UniProtKB/Swiss-Prot : 73 Spinocerebellar ataxia 21: A form of spinocerebellar ataxia, 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. SCA21 is characterized by onset in the first decades of life of slowly progressive relatively mild cerebellar ataxia associated with slight extrapyramidal features predominant in older patients and cognitive impairment predominant in younger patients.

Related Diseases for Spinocerebellar Ataxia 21

Diseases in the Spinocerebellar Ataxia 6 family:

Spinocerebellar Ataxia 31 Spinocerebellar Ataxia 29
Spinocerebellar Ataxia 34 Spinocerebellar Ataxia 1
Spinocerebellar Ataxia 7 Spinocerebellar Ataxia 2
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 21 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 36)
# Related Disease Score Top Affiliating Genes
1 spinocerebellar ataxia, autosomal recessive 21 32.8 TMEM240 SCYL1
2 hereditary ataxia 27.8 TTBK2 TMEM240 SPTBN2 KCNC3 FGF14 AFG3L2
3 autosomal dominant cerebellar ataxia 27.4 TTBK2 TMEM240 SPTBN2 PLEKHG4 KCNC3 FGF14
4 tremor 10.3
5 klebsiella pneumonia 10.2
6 movement disease 10.2
7 myoclonus 10.2
8 autosomal dominant cerebellar ataxia type iii 10.1 TTBK2 PLEKHG4
9 ataxia and polyneuropathy, adult-onset 10.0
10 spastic paraplegia 19, autosomal dominant 10.0 TTBK2 PLEKHG4
11 israeli tick typhus 10.0 SPTBN2 PLEKHG4
12 spinocerebellar ataxia 27 10.0 TMEM240 FGF14
13 brill-zinsser disease 10.0 SPTBN2 PLEKHG4
14 endemic typhus 10.0 SPTBN2 PLEKHG4
15 spinocerebellar ataxia, autosomal recessive 14 10.0 SPTBN2 AFG3L2
16 rocky mountain spotted fever 9.9 SPTBN2 PLEKHG4
17 spotted fever 9.9 SPTBN2 PLEKHG4
18 boutonneuse fever 9.8 SPTBN2 PLEKHG4
19 cerebellar ataxia type 41 9.8 KCNC3 AFG3L2
20 spinocerebellar ataxia 23 9.8 TMEM240 KCNC3
21 spinocerebellar ataxia 20 9.8 TMEM240 SPTBN2 PLEKHG4
22 epidemic typhus 9.7 SPTBN2 PLEKHG4
23 cerebral palsy, ataxic, autosomal recessive 9.7 SPTBN2 KCNC3
24 episodic ataxia, type 6 9.5 SPTBN2 KCNC3
25 episodic ataxia, type 2 9.5 SPTBN2 KCNC3
26 dentatorubral-pallidoluysian atrophy 9.2 KCNC3 FGF14
27 spinocerebellar ataxia 18 9.2 TTBK2 TMEM240 SPTBN2 PLEKHG4 AFG3L2
28 spastic paraplegia 25, autosomal recessive 9.1 TTBK2 PLEKHG4 KCNC3 FGF14
29 spastic paraplegia 34, x-linked 9.1 TTBK2 PLEKHG4 KCNC3 FGF14
30 spinocerebellar ataxia 30 9.0 TTBK2 SPTBN2 PLEKHG4 FGF14 AFG3L2
31 cerebellar ataxia type 9 9.0 SPTBN2 PLEKHG4 KCNC3 FGF14
32 spinocerebellar ataxia 25 9.0 TTBK2 TMEM240 PLEKHG4 FGF14 CNTN4
33 spinocerebellar ataxia 13 9.0 TTBK2 SPTBN2 KCNC3 FGF14
34 cerebellar disease 8.8 SPTBN2 PLEKHG4 KCNC3 FGF14 AFG3L2
35 episodic ataxia 8.7 TTBK2 SPTBN2 KCNC3 FGF14 AFG3L2
36 spinocerebellar ataxia 15 8.7 TTBK2 SPTBN2 KCNC3 CNTN4 AFG3L2

Graphical network of the top 20 diseases related to Spinocerebellar Ataxia 21:



Diseases related to Spinocerebellar Ataxia 21

Symptoms & Phenotypes for Spinocerebellar Ataxia 21

Human phenotypes related to Spinocerebellar Ataxia 21:

58 31 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of extrapyramidal motor function 58 31 hallmark (90%) Very frequent (99-80%) HP:0002071
2 gait ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002066
3 progressive cerebellar ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002073
4 intermittent microsaccadic pursuits 58 31 hallmark (90%) Very frequent (99-80%) HP:0007944
5 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
6 behavioral abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0000708
7 cognitive impairment 58 31 frequent (33%) Frequent (79-30%) HP:0100543
8 nystagmus 58 31 occasional (7.5%) Frequent (79-30%) HP:0000639
9 tremor 58 31 frequent (33%) Frequent (79-30%) HP:0001337
10 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
11 dysgraphia 58 31 frequent (33%) Frequent (79-30%) HP:0010526
12 rigidity 58 31 frequent (33%) Frequent (79-30%) HP:0002063
13 cerebellar vermis atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0006855
14 akinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002304
15 diplopia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000651
16 global developmental delay 31 HP:0001263
17 hyporeflexia 31 HP:0001265
18 cerebellar atrophy 31 HP:0001272
19 scanning speech 31 HP:0002168
20 aggressive behavior 31 HP:0000718
21 apathy 31 HP:0000741
22 impulsivity 31 HP:0100710
23 cogwheel rigidity 31 HP:0002396
24 limb ataxia 31 HP:0002070
25 parkinsonism 31 HP:0001300
26 slow saccadic eye movements 31 HP:0000514
27 postural tremor 31 HP:0002174
28 microsaccadic pursuit 31 HP:0007792

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
cognitive impairment
tremor
dysarthria
dysgraphia
hyporeflexia
more
Neurologic Behavioral Psychiatric Manifestations:
apathy
impulsivity
executive dysfunction
aggression

Head And Neck Eyes:
nystagmus
microsaccadic pursuit
slow saccades
square wave jerks

Clinical features from OMIM:

607454

UMLS symptoms related to Spinocerebellar Ataxia 21:


tremor, abnormality of extrapyramidal motor function, gait ataxia, scanning speech, cogwheel rigidity, cerebellar ataxia, static tremor

MGI Mouse Phenotypes related to Spinocerebellar Ataxia 21:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.17 AFG3L2 CNTN4 FGF14 KCNC3 SCYL1 SPTBN2

Drugs & Therapeutics for Spinocerebellar Ataxia 21

Search Clinical Trials , NIH Clinical Center for Spinocerebellar Ataxia 21

Genetic Tests for Spinocerebellar Ataxia 21

Genetic tests related to Spinocerebellar Ataxia 21:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia Type 21 29 TMEM240

Anatomical Context for Spinocerebellar Ataxia 21

MalaCards organs/tissues related to Spinocerebellar Ataxia 21:

40
Eye, Cerebellum, Spinal Cord, Liver

Publications for Spinocerebellar Ataxia 21

Articles related to Spinocerebellar Ataxia 21:

(show all 14)
# Title Authors PMID Year
1
TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment. 6 56 61
25070513 2014
2
Clinical features and genetic analysis of a new form of spinocerebellar ataxia. 56 6
11160961 2001
3
Slowly progressive spinocerebellar ataxia with extrapyramidal signs and mild cognitive impairment (SCA21). 56 61
18418688 2008
4
On CALFAN syndrome: report of a patient with a novel variant in SCYL1 gene and recurrent respiratory failure. 6
30531813 2019
5
Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia. 6
26581903 2015
6
EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias. 6
20050888 2010
7
A new locus for spinocerebellar ataxia (SCA21) maps to chromosome 7p21.3-p15.1. 56
12402269 2002
8
Hereditary Ataxia Overview 6
20301317 1998
9
The TMEM240 Protein, Mutated in SCA21, Is Expressed in Purkinje Cells and Synaptic Terminals. 61
32002801 2020
10
The movement disorder spectrum of SCA21 (ATX-TMEM240): 3 novel families and systematic review of the literature. 61
30522958 2019
11
Lysosomal dysfunction and early glial activation are involved in the pathogenesis of spinocerebellar ataxia type 21 caused by mutant transmembrane protein 240. 61
30184469 2018
12
A Japanese Family of Spinocerebellar Ataxia Type 21: Clinical and Neuropathological Studies. 61
29687291 2018
13
Spinocerebellar Ataxia-21 in a Turkish Child. 61
29720801 2018
14
Spinocerebellar ataxia type 21 exists in the Chinese Han population. 61
26813285 2016

Variations for Spinocerebellar Ataxia 21

ClinVar genetic disease variations for Spinocerebellar Ataxia 21:

6 (show all 11) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TMEM240 NM_001114748.2(TMEM240):c.489C>G (p.Tyr163Ter)SNV Pathogenic 161193 rs606231452 1:1470772-1470772 1:1535392-1535392
2 TMEM240 NM_001114748.2(TMEM240):c.346C>T (p.Arg116Cys)SNV Pathogenic 161194 rs606231453 1:1470996-1470996 1:1535616-1535616
3 TMEM240 NM_001114748.2(TMEM240):c.239C>T (p.Thr80Met)SNV Pathogenic 161195 rs606231454 1:1471103-1471103 1:1535723-1535723
4 TMEM240 NM_001114748.2(TMEM240):c.511C>T (p.Arg171Trp)SNV Pathogenic 161196 rs606231455 1:1470750-1470750 1:1535370-1535370
5 SCYL1 NM_020680.4(SCYL1):c.937del (p.Val313fs)deletion Pathogenic 218907 rs864309664 11:65298186-65298186 11:65530715-65530715
6 SCYL1 NM_020680.4(SCYL1):c.1507_1508TG[1] (p.Ala504fs)short repeat Pathogenic 218908 rs864309665 11:65303544-65303545 11:65536073-65536074
7 SCYL1 NM_020680.4(SCYL1):c.1230+1G>ASNV Pathogenic 218909 rs864309666 11:65300277-65300277 11:65532806-65532806
8 SCYL1 NM_020680.4(SCYL1):c.1636C>T (p.Gln546Ter)SNV Pathogenic 218910 rs864309667 11:65303790-65303790 11:65536319-65536319
9 SCYL1 NM_020680.4(SCYL1):c.1534dup (p.Cys512fs)duplication Pathogenic 691875 11:65303570-65303571 11:65536099-65536100
10 TMEM240 NM_001114748.2(TMEM240):c.509C>T (p.Pro170Leu)SNV Pathogenic/Likely pathogenic 161192 rs606231451 1:1470752-1470752 1:1535372-1535372
11 TMEM240 NM_001114748.2(TMEM240):c.343G>A (p.Val115Met)SNV Benign 523023 rs1045410944 1:1470999-1470999 1:1535619-1535619

UniProtKB/Swiss-Prot genetic disease variations for Spinocerebellar Ataxia 21:

73
# Symbol AA change Variation ID SNP ID
1 TMEM240 p.Thr80Met VAR_071906 rs606231454
2 TMEM240 p.Arg116Cys VAR_071907 rs606231453
3 TMEM240 p.Glu149Lys VAR_071908 rs546291208
4 TMEM240 p.Pro170Leu VAR_071909 rs606231451
5 TMEM240 p.Arg171Trp VAR_071910 rs606231455

Expression for Spinocerebellar Ataxia 21

Search GEO for disease gene expression data for Spinocerebellar Ataxia 21.

Pathways for Spinocerebellar Ataxia 21

Pathways related to Spinocerebellar Ataxia 21 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.05 SPTBN2 KCNC3 FGF14 AFG3L2

GO Terms for Spinocerebellar Ataxia 21

Biological processes related to Spinocerebellar Ataxia 21 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 axonogenesis GO:0007409 8.96 CNTN4 AFG3L2
2 regulation of synaptic plasticity GO:0048167 8.62 FGF14 CNTN4

Sources for Spinocerebellar Ataxia 21

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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