SCAR4
MCID: SPN288
MIFTS: 40

Spinocerebellar Ataxia, Autosomal Recessive 4 (SCAR4)

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 4

MalaCards integrated aliases for Spinocerebellar Ataxia, Autosomal Recessive 4:

Name: Spinocerebellar Ataxia, Autosomal Recessive 4 57 72 13 44 70
Scar4 57 12 20 58 72
Scasi 57 12 20 58 72
Autosomal Recessive Cerebellar Ataxia-Saccadic Intrusion Syndrome 12 58 29 6
Spinocerebellar Ataxia with Saccadic Intrusions 57 12 20 72
Autosomal Recessive Spinocerebellar Ataxia 4 12 15
Spinocerebellar Ataxia 24 12 72
Sca24 12 72
Spinocerebellar Ataxia with Saccadic Intrusions; Scasi 57
Spinocerebellar Ataxia 24, Formerly; Sca24, Formerly 57
Spinocerebellar Ataxia Autosomal Recessive 4 20
Spinocerebellar Ataxia 24, Formerly 57
Sca24, Formerly 57

Characteristics:

Orphanet epidemiological data:

58
autosomal recessive cerebellar ataxia-saccadic intrusion syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
variable age at onset (range infancy to adulthood)
some patients become wheelchair-bound in adulthood


HPO:

31
spinocerebellar ataxia, autosomal recessive 4:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity adult onset


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Spinocerebellar Ataxia, Autosomal Recessive 4

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 95434 Definition A rare hereditary ataxia characterized by a progressive cerebellar ataxia associated with disruption of visual fixation by saccadic intrusions (overshooting horizontal saccades with macrosaccadic oscillations and increased velocity of larger saccades). It presents with progressive gait, trunk and limb ataxia with pyramidal tract signs (increased tendon reflexes and Babinski sign), myoclonic jerks, fasciculations, cerebellar dysarthria, sensorimotor axonal neuropathy with impaired joint position, vibration, temperature, pain sensations, pes cavus, and saccadic intrusions with characteristic overshooting horizontal saccades, macrosaccadic oscillations, and increased velocity of larger saccades, without other eye movement disturbances.

MalaCards based summary : Spinocerebellar Ataxia, Autosomal Recessive 4, also known as scar4, is related to spinocerebellar ataxia, autosomal recessive 24 and vps13d movement disorder, and has symptoms including myoclonus, gait ataxia and muscular fasciculation. An important gene associated with Spinocerebellar Ataxia, Autosomal Recessive 4 is VPS13D (Vacuolar Protein Sorting 13 Homolog D). Affiliated tissues include eye, cerebellum and spinal cord, and related phenotypes are abnormal pyramidal sign and gait ataxia

Disease Ontology : 12 An autosomal recessive cerebellar ataxia characterized by ataxic gait with spasticity, hyperreflexia of the lower limbs, and mitochondrial defects that has material basis in homozygous or compound heterozygous mutation in VPS13D on chromosome 1p36.22-p36.21.

OMIM® : 57 SCAR4 is an autosomal recessive neurologic disorder characterized by abnormal movements. Most patients have ataxic gait with spasticity and hyperreflexia of the lower limbs resulting in difficulty walking. The age at onset is highly variable: some have onset in early childhood with delayed walking, whereas others have onset of gait difficulties in adulthood. Additional features may include dysarthria, oculomotor abnormalities, distal sensory impairment, dystonia, chorea, hypotonia, pyramidal signs, and cerebellar atrophy on brain imaging. The disorder is slowly progressive. Some patients with onset in childhood may have global developmental delay with mild intellectual disability (summary by Seong et al., 2018). (607317) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Spinocerebellar ataxia, autosomal recessive 4: 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. SCAR4 patients manifest ataxic gait with spasticity and hyperreflexia of the lower limbs resulting in difficulty walking. The age at onset is highly variable, ranging from early childhood to adulthood.

Related Diseases for Spinocerebellar Ataxia, Autosomal Recessive 4

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 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 spinocerebellar ataxia, autosomal recessive 24 11.4
2 vps13d movement disorder 11.0
3 spinocerebellar ataxia 31 10.1 DAB1 CACNA1A
4 adolescence-adult electroclinical syndrome 10.0 DAB1 CACNA1A
5 autosomal recessive cerebellar ataxia 10.0 ZNF592 VPS13D CACNA1A
6 familial adult myoclonic epilepsy 9.9 VPS13C DAB1 CACNA1A
7 spinocerebellar ataxia 17 9.9 VPS13A CACNA1A
8 spinocerebellar ataxia, autosomal recessive 3 9.8 ZNF592 NCKAP1
9 spinocerebellar ataxia 10 9.8 DAB1 CACNA1A
10 huntington disease-like 2 9.8 VPS13A CACNA1A
11 choreatic disease 9.6 VPS13D VPS13C VPS13A CACNA1A
12 choreoacanthocytosis 9.6 VPS13D VPS13C VPS13B VPS13A
13 cohen syndrome 9.6 VPS13D VPS13C VPS13B VPS13A

Graphical network of the top 20 diseases related to Spinocerebellar Ataxia, Autosomal Recessive 4:



Diseases related to Spinocerebellar Ataxia, Autosomal Recessive 4

Symptoms & Phenotypes for Spinocerebellar Ataxia, Autosomal Recessive 4

Human phenotypes related to Spinocerebellar Ataxia, Autosomal Recessive 4:

58 31 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal pyramidal sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0007256
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 limb ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002070
5 truncal ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002078
6 abnormal lower motor neuron morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0002366
7 abnormal visual fixation 58 31 hallmark (90%) Very frequent (99-80%) HP:0025404
8 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
9 pes cavus 58 31 frequent (33%) Frequent (79-30%) HP:0001761
10 fasciculations 58 31 frequent (33%) Frequent (79-30%) HP:0002380
11 dyslexia 58 31 frequent (33%) Frequent (79-30%) HP:0010522
12 impaired proprioception 58 31 frequent (33%) Frequent (79-30%) HP:0010831
13 unsteady gait 58 31 frequent (33%) Frequent (79-30%) HP:0002317
14 sensorimotor neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0007141
15 hypermetric saccades 58 31 frequent (33%) Frequent (79-30%) HP:0007338
16 myoclonus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001336
17 microcephaly 31 very rare (1%) HP:0000252
18 intellectual disability, mild 31 very rare (1%) HP:0001256
19 motor delay 31 very rare (1%) HP:0001270
20 abnormality of the cerebral white matter 31 very rare (1%) HP:0002500
21 spasticity 31 HP:0001257
22 hyperreflexia 31 HP:0001347
23 abnormality of eye movement 58 Frequent (79-30%)
24 nystagmus 31 HP:0000639
25 ataxia 31 HP:0001251
26 tremor 31 HP:0001337
27 dystonia 31 HP:0001332
28 upper motor neuron dysfunction 58 Very frequent (99-80%)
29 babinski sign 31 HP:0003487
30 sensory impairment 58 Very frequent (99-80%)
31 distal muscle weakness 31 HP:0002460
32 frequent falls 31 HP:0002359
33 muscular hypotonia of the trunk 31 HP:0008936
34 distal amyotrophy 31 HP:0003693
35 peripheral axonal neuropathy 31 HP:0003477
36 abnormal saccadic eye movements 58 Frequent (79-30%)
37 macrosaccadic oscillations 31 HP:0032105

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
spasticity
hyperreflexia
dysarthria
tremor
dystonia
more
Skeletal Feet:
pes cavus

Head And Neck Head:
microcephaly (in some patients)

Head And Neck Eyes:
nystagmus
macrosaccadic oscillations
difficulty reading
overshooting horizontal saccades
increased velocity of larger saccades

Muscle Soft Tissue:
distal muscle weakness
distal muscle atrophy
axial hypotonia
abnormal mitochondria seen on muscle biopsy

Neurologic Peripheral Nervous System:
impaired distal sensation
sensorimotor axonal neuropathy

Clinical features from OMIM®:

607317 (Updated 05-Apr-2021)

UMLS symptoms related to Spinocerebellar Ataxia, Autosomal Recessive 4:


myoclonus; gait ataxia; muscular fasciculation; abnormal pyramidal signs

Drugs & Therapeutics for Spinocerebellar Ataxia, Autosomal Recessive 4

Search Clinical Trials , NIH Clinical Center for Spinocerebellar Ataxia, Autosomal Recessive 4

Cochrane evidence based reviews: spinocerebellar ataxia, autosomal recessive 4

Genetic Tests for Spinocerebellar Ataxia, Autosomal Recessive 4

Genetic tests related to Spinocerebellar Ataxia, Autosomal Recessive 4:

# Genetic test Affiliating Genes
1 Autosomal Recessive Cerebellar Ataxia-Saccadic Intrusion Syndrome 29 VPS13D

Anatomical Context for Spinocerebellar Ataxia, Autosomal Recessive 4

MalaCards organs/tissues related to Spinocerebellar Ataxia, Autosomal Recessive 4:

40
Eye, Cerebellum, Spinal Cord

Publications for Spinocerebellar Ataxia, Autosomal Recessive 4

Articles related to Spinocerebellar Ataxia, Autosomal Recessive 4:

# Title Authors PMID Year
1
Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects. 6 57 61
29604224 2018
2
Recessive mutations in VPS13D cause childhood onset movement disorders. 6 57
29518281 2018
3
A form of inherited cerebellar ataxia with saccadic intrusions, increased saccadic speed, sensory neuropathy, and myoclonus. 6 57
11960835 2002
4
Pathogenesis of clinical signs in recessive ataxia with saccadic intrusions. 57
14681893 2003
5
A Nanostructured Lipid System to Improve the Oral Bioavailability of Ruthenium(II) Complexes for the Treatment of Infections Caused by Mycobacterium tuberculosis. 61
30574128 2018
6
SCARN a Novel Class of SCAR Protein That Is Required for Root-Hair Infection during Legume Nodulation. 61
26517270 2015

Variations for Spinocerebellar Ataxia, Autosomal Recessive 4

ClinVar genetic disease variations for Spinocerebellar Ataxia, Autosomal Recessive 4:

6 (show all 27)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 VPS13D NM_015378.4(VPS13D):c.3569G>A (p.Gly1190Asp) SNV Pathogenic 561198 rs1557680919 GRCh37: 1:12337214-12337214
GRCh38: 1:12277157-12277157
2 VPS13D NM_015378.4(VPS13D):c.3316C>T (p.Gln1106Ter) SNV Pathogenic 561199 rs1557680710 GRCh37: 1:12336961-12336961
GRCh38: 1:12276904-12276904
3 VPS13D NM_015378.4(VPS13D):c.12629C>T (p.Ala4210Val) SNV Pathogenic 561200 rs746736545 GRCh37: 1:12520418-12520418
GRCh38: 1:12460363-12460363
4 VPS13D NM_015378.4(VPS13D):c.5409C>A (p.Tyr1803Ter) SNV Pathogenic 561201 rs1557684974 GRCh37: 1:12343568-12343568
GRCh38: 1:12283511-12283511
5 VPS13D NM_015378.4(VPS13D):c.7332_7333TG[1] (p.Val2445fs) Microsatellite Pathogenic 561202 rs1557705968 GRCh37: 1:12378312-12378313
GRCh38: 1:12318255-12318256
6 VPS13D NM_015378.4(VPS13D):c.10562A>G (p.Asn3521Ser) SNV Pathogenic 561203 rs1557737087 GRCh37: 1:12428636-12428636
GRCh38: 1:12368581-12368581
7 VPS13D NM_015378.4(VPS13D):c.12683G>A (p.Arg4228Gln) SNV Pathogenic 561204 rs1557478316 GRCh37: 1:12557574-12557574
GRCh38: 1:12497520-12497520
8 VPS13D NM_015378.4(VPS13D):c.12350C>G (p.Ser4117Ter) SNV Pathogenic 983262 GRCh37: 1:12516070-12516070
GRCh38: 1:12456014-12456014
9 VPS13D NM_015378.4(VPS13D):c.2020C>T (p.Arg674Ter) SNV Pathogenic 807523 rs756025227 GRCh37: 1:12331098-12331098
GRCh38: 1:12271041-12271041
10 VPS13D NM_015378.4(VPS13D):c.12743C>A (p.Ala4248Glu) SNV Likely pathogenic 807716 rs779850187 GRCh37: 1:12557634-12557634
GRCh38: 1:12497580-12497580
11 VPS13D NM_015378.4(VPS13D):c.12530G>A (p.Gly4177Asp) SNV Likely pathogenic 983263 GRCh37: 1:12520319-12520319
GRCh38: 1:12460264-12460264
12 VPS13D NM_015378.4(VPS13D):c.12416C>T (p.Ala4139Val) SNV Likely pathogenic 932894 GRCh37: 1:12516136-12516136
GRCh38: 1:12456080-12456080
13 VPS13D NM_015378.4(VPS13D):c.946C>T (p.Arg316Ter) SNV Likely pathogenic 933227 GRCh37: 1:12317996-12317996
GRCh38: 1:12257939-12257939
14 VPS13D NM_015378.4(VPS13D):c.1183C>T (p.Arg395Ter) SNV Likely pathogenic 1029390 GRCh37: 1:12320822-12320822
GRCh38: 1:12260765-12260765
15 VPS13D NM_015378.4(VPS13D):c.12227G>A (p.Gly4076Glu) SNV Uncertain significance 1029391 GRCh37: 1:12476774-12476774
GRCh38: 1:12416721-12416721
16 VPS13D NM_015378.4(VPS13D):c.293A>G (p.Asn98Ser) SNV Uncertain significance 1029392 GRCh37: 1:12304420-12304420
GRCh38: 1:12244363-12244363
17 VPS13D NM_015378.4(VPS13D):c.4451-16A>G SNV Uncertain significance 1029393 GRCh37: 1:12339540-12339540
GRCh38: 1:12279483-12279483
18 VPS13D NM_015378.4(VPS13D):c.530A>G (p.Lys177Arg) SNV Uncertain significance 1029394 GRCh37: 1:12309362-12309362
GRCh38: 1:12249305-12249305
19 VPS13D NM_015378.4(VPS13D):c.614T>C (p.Ile205Thr) SNV Uncertain significance 1029395 GRCh37: 1:12313828-12313828
GRCh38: 1:12253771-12253771
20 VPS13D NM_015378.4(VPS13D):c.8363C>G (p.Pro2788Arg) SNV Uncertain significance 1029396 GRCh37: 1:12393358-12393358
GRCh38: 1:12333301-12333301
21 VPS13D NM_015378.4(VPS13D):c.9157A>G (p.Ile3053Val) SNV Uncertain significance 1029397 GRCh37: 1:12408967-12408967
GRCh38: 1:12348910-12348910
22 VPS13D NM_015378.4(VPS13D):c.2065C>T (p.Arg689Trp) SNV Uncertain significance 996333 rs775767366 GRCh37: 1:12331143-12331143
GRCh38: 1:12271086-12271086
23 VPS13D NM_015378.4(VPS13D):c.4022C>T (p.Ser1341Leu) SNV Uncertain significance 996334 rs12407578 GRCh37: 1:12337667-12337667
GRCh38: 1:12277610-12277610
24 VPS13D NM_015378.4(VPS13D):c.10169G>A (p.Arg3390Gln) SNV Uncertain significance 1027981 GRCh37: 1:12422803-12422803
GRCh38: 1:12362747-12362747
25 VPS13D NM_015378.4(VPS13D):c.7196G>T (p.Arg2399Leu) SNV Uncertain significance 634498 rs201376188 GRCh37: 1:12378176-12378176
GRCh38: 1:12318119-12318119
26 VPS13D NM_015378.4(VPS13D):c.9304C>G (p.Pro3102Ala) SNV Uncertain significance 873478 GRCh37: 1:12409304-12409304
GRCh38: 1:12349247-12349247
27 VPS13D NM_015378.4(VPS13D):c.11459A>T (p.Asn3820Ile) SNV Uncertain significance 873479 GRCh37: 1:12445407-12445407
GRCh38: 1:12385348-12385348

UniProtKB/Swiss-Prot genetic disease variations for Spinocerebellar Ataxia, Autosomal Recessive 4:

72
# Symbol AA change Variation ID SNP ID
1 VPS13D p.Thr865Ala VAR_080911 rs138395840
2 VPS13D p.Gly1200Asp VAR_080912 rs768331333
3 VPS13D p.Leu2900Ser VAR_080913
4 VPS13D p.Arg3253Gln VAR_080914 rs119162557
5 VPS13D p.Asn3521Ser VAR_080915 rs155773708
6 VPS13D p.Arg4228Gln VAR_080916 rs155747831
7 VPS13D p.Gly1190Asp VAR_081498 rs155768091
8 VPS13D p.Ala4210Val VAR_081505 rs746736545

Expression for Spinocerebellar Ataxia, Autosomal Recessive 4

Search GEO for disease gene expression data for Spinocerebellar Ataxia, Autosomal Recessive 4.

Pathways for Spinocerebellar Ataxia, Autosomal Recessive 4

GO Terms for Spinocerebellar Ataxia, Autosomal Recessive 4

Cellular components related to Spinocerebellar Ataxia, Autosomal Recessive 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell leading edge GO:0031252 9.16 JMY ARPC3
2 filamentous actin GO:0031941 8.96 NCKAP1 ARPC3
3 extrinsic component of membrane GO:0019898 8.8 VPS13D VPS13C VPS13A

Biological processes related to Spinocerebellar Ataxia, Autosomal Recessive 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Arp2/3 complex-mediated actin nucleation GO:0034314 9.33 WHAMM JMY ARPC3
2 Golgi to endosome transport GO:0006895 9.32 VPS13C VPS13A
3 actin polymerization-dependent cell motility GO:0070358 9.26 JMY ARPC3
4 protein targeting to vacuole GO:0006623 9.13 VPS13D VPS13C VPS13A
5 protein retention in Golgi apparatus GO:0045053 8.8 VPS13D VPS13C VPS13A

Molecular functions related to Spinocerebellar Ataxia, Autosomal Recessive 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Arp2/3 complex binding GO:0071933 8.62 WHAMM JMY

Sources for Spinocerebellar Ataxia, Autosomal Recessive 4

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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