SCAR21
MCID: SPN381
MIFTS: 34

Spinocerebellar Ataxia, Autosomal Recessive 21 (SCAR21)

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, Autosomal Recessive 21

MalaCards integrated aliases for Spinocerebellar Ataxia, Autosomal Recessive 21:

Name: Spinocerebellar Ataxia, Autosomal Recessive 21 57 29 6
Scar21 57 12 59 74
Acute Infantile Liver Failure-Cerebellar Ataxia-Peripheral Sensory Motor Neuropathy Syndrome 12 59
Spinocerebellar Ataxia, Autosomal Recessive 21, with Hepatopathy 57 74
Autosomal Recessive Spinocerebellar Ataxia 21 12 15
Autosomal Recessive Spinocerebellar Ataxia 21 with Hepatopathy 12
Autosomal Recessive Spinocerebellar Ataxia Type 21 59
Spinocerebellar Ataxia, Autosomal Recessive, 21 74

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
three patients from 2 unrelated families have been reported (last curated december 2015)
onset of episodic liver failure in first 2 years of life
liver failure episodes associated with fever
liver failure episodes cease in later childhood
onset of ataxia in early childhood


HPO:

32
spinocerebellar ataxia, autosomal recessive 21:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0111155
Orphanet 59 ORPHA466794

Summaries for Spinocerebellar Ataxia, Autosomal Recessive 21

UniProtKB/Swiss-Prot : 74 Spinocerebellar ataxia, autosomal recessive, 21: 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. SCAR21 is characterized by cerebellar atrophy and ataxia with onset in early childhood. Patients also manifest recurrent episodes of liver failure, hepatic fibrosis and a peripheral neuropathy.

MalaCards based summary : Spinocerebellar Ataxia, Autosomal Recessive 21, also known as scar21, is related to spastic paraplegia 5a and spinocerebellar ataxia 21. An important gene associated with Spinocerebellar Ataxia, Autosomal Recessive 21 is SCYL1 (SCY1 Like Pseudokinase 1). Affiliated tissues include liver, spinal cord and cerebellum, and related phenotypes are global developmental delay and intellectual disability, mild

Disease Ontology : 12 An autosomal recessive cerebellar ataxia that has material basis in homozygous or compound heterozygous mutation in the SCYL1 gene on chromosome 11q13.

OMIM : 57 Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur (summary by Schmidt et al., 2015). (616719)

Related Diseases for Spinocerebellar Ataxia, Autosomal Recessive 21

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 Spinocerebellar Ataxia Autosomal Recessive 5

Diseases related to Spinocerebellar Ataxia, Autosomal Recessive 21 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 18)
# Related Disease Score Top Affiliating Genes
1 spastic paraplegia 5a 10.4 GBA2 CYP7B1
2 spinocerebellar ataxia 21 10.4 TMEM240 SCYL1
3 spastic paraplegia 5a, autosomal recessive 10.2 PNPLA6 CYP7B1
4 spastic paraplegia 43, autosomal recessive 10.2 PNPLA6 CYP7B1
5 sjogren-larsson syndrome 10.2 PNPLA6 FA2H
6 polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract 10.0 PNPLA6 FA2H
7 spastic paraplegia 24, autosomal recessive 9.9 SPG7 CYP7B1
8 spastic paraplegia 15, autosomal recessive 9.8 SPG7 FA2H
9 autosomal recessive cerebellar ataxia 9.7 UBA5 SPG7 GBA2
10 spastic paraparesis 9.7 SPG7 FA2H
11 spastic ataxia 9.7 SPG7 KIF1C
12 spinocerebellar ataxia 28 9.5 SPG7 GRM1
13 aceruloplasminemia 9.5 GRM1 GBA2 FA2H ATP13A2
14 paraplegia 9.2 SPG7 PNPLA6 FA2H CYP7B1
15 spasticity 9.2 SPG7 CAPN1
16 hereditary spastic paraplegia 7.8 SPG7 PNPLA6 KIF1C GBA2 FA2H CYP7B1
17 spastic paraplegia 76, autosomal recessive 5.8 XRCC1 UBA5 SPG7 PNPLA6 PLD3 KIF1C
18 spastic paraplegia 73, autosomal dominant 5.8 XRCC1 UBA5 SPG7 PNPLA6 PLD3 KIF1C

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



Diseases related to Spinocerebellar Ataxia, Autosomal Recessive 21

Symptoms & Phenotypes for Spinocerebellar Ataxia, Autosomal Recessive 21

Human phenotypes related to Spinocerebellar Ataxia, Autosomal Recessive 21:

59 32 (show all 33)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
2 intellectual disability, mild 59 32 occasional (7.5%) Frequent (79-30%) HP:0001256
3 fever 59 32 frequent (33%) Frequent (79-30%) HP:0001945
4 hepatic fibrosis 59 32 frequent (33%) Frequent (79-30%) HP:0001395
5 gait ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0002066
6 intention tremor 59 32 frequent (33%) Frequent (79-30%) HP:0002080
7 paresthesia 59 32 frequent (33%) Frequent (79-30%) HP:0003401
8 acute hepatic failure 59 32 frequent (33%) Frequent (79-30%) HP:0006554
9 progressive cerebellar ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0002073
10 saccadic smooth pursuit 59 32 frequent (33%) Frequent (79-30%) HP:0001152
11 hyporeflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001265
12 cerebellar vermis atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0006855
13 generalized limb muscle atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0009055
14 distal lower limb muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0009053
15 frequent falls 59 32 frequent (33%) Frequent (79-30%) HP:0002359
16 hepatosplenomegaly 59 32 frequent (33%) Frequent (79-30%) HP:0001433
17 sensory impairment 59 32 frequent (33%) Frequent (79-30%) HP:0003474
18 dysmetric saccades 59 32 frequent (33%) Frequent (79-30%) HP:0000641
19 stuttering 59 32 frequent (33%) Frequent (79-30%) HP:0025268
20 spasticity 59 32 occasional (7.5%) Very rare (<4-1%) HP:0001257
21 hyperreflexia 59 32 occasional (7.5%) Very rare (<4-1%) HP:0001347
22 talipes equinovarus 59 32 occasional (7.5%) Very rare (<4-1%) HP:0001762
23 optic atrophy 59 32 very rare (1%) Very rare (<4-1%) HP:0000648
24 tremor 32 HP:0001337
25 splenomegaly 32 HP:0001744
26 hepatomegaly 32 HP:0002240
27 peripheral neuropathy 59 Frequent (79-30%)
28 reduced visual acuity 59 Excluded (0%)
29 motor delay 32 HP:0001270
30 hepatic failure 32 HP:0001399
31 cerebellar atrophy 32 HP:0001272
32 sensorimotor neuropathy 32 HP:0007141
33 distal sensory impairment 32 HP:0002936

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
tremor
cerebellar atrophy
frequent falls
cerebellar ataxia
delayed motor development
more
Abdomen Liver:
hepatomegaly
hepatic fibrosis
liver failure, episodic, during first decade

Skeletal Feet:
pes equinovarus (1 patient)

Muscle Soft Tissue:
muscle atrophy, upper and lower limbs
muscle weakness, distal, lower limbs, due to peripheral neuropathy

Abdomen Spleen:
splenomegaly

Neurologic Peripheral Nervous System:
hyporeflexia
sensorimotor neuropathy
distal sensory impairment

Head And Neck Eyes:
saccadic pursuit
cerebellar oculomotor disturbance
subclinical optic atrophy (1 family)
preserved vision

Clinical features from OMIM:

616719

Drugs & Therapeutics for Spinocerebellar Ataxia, Autosomal Recessive 21

Search Clinical Trials , NIH Clinical Center for Spinocerebellar Ataxia, Autosomal Recessive 21

Genetic Tests for Spinocerebellar Ataxia, Autosomal Recessive 21

Genetic tests related to Spinocerebellar Ataxia, Autosomal Recessive 21:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia, Autosomal Recessive 21 29 SCYL1

Anatomical Context for Spinocerebellar Ataxia, Autosomal Recessive 21

MalaCards organs/tissues related to Spinocerebellar Ataxia, Autosomal Recessive 21:

41
Liver, Spinal Cord, Cerebellum

Publications for Spinocerebellar Ataxia, Autosomal Recessive 21

Articles related to Spinocerebellar Ataxia, Autosomal Recessive 21:

# Title Authors PMID Year
1
Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia. 8
26581903 2015
2
An early onset progressive motor neuron disorder in Scyl1-deficient mice is associated with mislocalization of TDP-43. 8
23175812 2012
3
Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration. 8
17571074 2007
4
Variant in SCYL1 gene causes aberrant splicing in a family with cerebellar ataxia, recurrent episodes of liver failure, and growth retardation. 38
30258122 2019
5
Hereditary ataxias and paraparesias: clinical and genetic update. 38
29847346 2018
6
Spinocerebellar Ataxia-21 in a Turkish Child. 38
29720801 2018

Variations for Spinocerebellar Ataxia, Autosomal Recessive 21

ClinVar genetic disease variations for Spinocerebellar Ataxia, Autosomal Recessive 21:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 SCYL1 NM_020680.4(SCYL1): c.1412C> T (p.Ala471Val) single nucleotide variant Likely pathogenic rs1554969894 11:65303449-65303449 11:65535978-65535978

Expression for Spinocerebellar Ataxia, Autosomal Recessive 21

Search GEO for disease gene expression data for Spinocerebellar Ataxia, Autosomal Recessive 21.

Pathways for Spinocerebellar Ataxia, Autosomal Recessive 21

GO Terms for Spinocerebellar Ataxia, Autosomal Recessive 21

Cellular components related to Spinocerebellar Ataxia, Autosomal Recessive 21 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 9.97 TMEM240 SPG7 SCYL1 PNPLA6 PLD3 GRM1
2 endoplasmic reticulum membrane GO:0005789 9.43 PNPLA6 PLD3 GBA2 FA2H CYP7B1 CPT1C
3 endoplasmic reticulum GO:0005783 9.17 PNPLA6 PLD3 KIF1C GBA2 FA2H CYP7B1

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

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.1 PNPLA6 PLD3 GBA2 FA2H CYP7B1 CPT1C

Molecular functions related to Spinocerebellar Ataxia, Autosomal Recessive 21 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.1 SPG7 PNPLA6 PLD3 GBA2 CAPN1 ATP13A2

Sources for Spinocerebellar Ataxia, Autosomal Recessive 21

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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