SCAR16
MCID: SPN273
MIFTS: 37

Spinocerebellar Ataxia, Autosomal Recessive 16 (SCAR16)

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 16

MalaCards integrated aliases for Spinocerebellar Ataxia, Autosomal Recessive 16:

Name: Spinocerebellar Ataxia, Autosomal Recessive 16 57 29 6 72
Scar16 57 59 74
Autosomal Recessive Spinocerebellar Ataxia 16 12 15
Autosomal Recessive Cerebellar Ataxia Due to Stub1 Deficiency 59
Ataxia, Spinocerebellar, Autosomal Recessive, Type 16 40
Spinocerebellar Ataxia Autosomal Recessive Type 16 59
Spinocerebellar Ataxia, Autosomal Recessive, 16 74

Characteristics:

Orphanet epidemiological data:

59
autosomal recessive cerebellar ataxia due to stub1 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset usually in second decade
variable age at onset (range 2 to 48 years)


HPO:

32
spinocerebellar ataxia, autosomal recessive 16:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0080029
ICD10 via Orphanet 34 G11.1
Orphanet 59 ORPHA412057
UMLS 72 C4014261

Summaries for Spinocerebellar Ataxia, Autosomal Recessive 16

UniProtKB/Swiss-Prot : 74 Spinocerebellar ataxia, autosomal recessive, 16: 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. SCAR16 is characterized by truncal and limb ataxia resulting in gait instability. Additionally, patients may show dysarthria, nystagmus, spasticity of the lower limbs, and mild peripheral sensory neuropathy.

MalaCards based summary : Spinocerebellar Ataxia, Autosomal Recessive 16, also known as scar16, is related to ataxia and polyneuropathy, adult-onset and autosomal dominant cerebellar ataxia, and has symptoms including ataxia, truncal An important gene associated with Spinocerebellar Ataxia, Autosomal Recessive 16 is STUB1 (STIP1 Homology And U-Box Containing Protein 1), and among its related pathways/superpathways are Chks in Checkpoint Regulation and Proteolysis Role of Parkin in the Ubiquitin-Proteasomal Pathway. Affiliated tissues include eye, spinal cord and cerebellum, and related phenotypes are dysarthria and limb ataxia

OMIM : 57 Autosomal recessive spinocerebellar ataxia-16 is a progressive neurologic disorder characterized by truncal and limb ataxia resulting in gait instability. Most patients have onset in the teenage years, although earlier and later onset have been reported. Additional features may include dysarthria, nystagmus, spasticity of the lower limbs, and mild peripheral sensory neuropathy (summary by Shi et al., 2013). (615768)

Related Diseases for Spinocerebellar Ataxia, Autosomal Recessive 16

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

# Related Disease Score Top Affiliating Genes
1 ataxia and polyneuropathy, adult-onset 10.4
2 autosomal dominant cerebellar ataxia 10.4
3 aceruloplasminemia 10.2

Symptoms & Phenotypes for Spinocerebellar Ataxia, Autosomal Recessive 16

Human phenotypes related to Spinocerebellar Ataxia, Autosomal Recessive 16:

59 32 (show top 50) (show all 58)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysarthria 59 32 hallmark (90%) Very frequent (99-80%) HP:0001260
2 limb ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002070
3 truncal ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002078
4 cerebellar atrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0001272
5 impaired proprioception 59 32 frequent (33%) Frequent (79-30%) HP:0010831
6 arachnodactyly 59 32 frequent (33%) Frequent (79-30%) HP:0001166
7 difficulty walking 59 32 frequent (33%) Frequent (79-30%) HP:0002355
8 adducted thumb 59 32 frequent (33%) Frequent (79-30%) HP:0001181
9 postural instability 59 32 frequent (33%) Frequent (79-30%) HP:0002172
10 unsteady gait 59 32 frequent (33%) Frequent (79-30%) HP:0002317
11 abnormal motor evoked potentials 59 32 frequent (33%) Frequent (79-30%) HP:0012896
12 progeroid facial appearance 59 32 frequent (33%) Frequent (79-30%) HP:0005328
13 nystagmus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000639
14 dysphagia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002015
15 hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000365
16 global developmental delay 59 32 occasional (7.5%) Occasional (29-5%) HP:0001263
17 cognitive impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0100543
18 memory impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0002354
19 ophthalmoplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000602
20 hypogonadism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000135
21 cerebellar hypoplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001321
22 rigidity 59 32 occasional (7.5%) Occasional (29-5%) HP:0002063
23 postural tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0002174
24 horizontal nystagmus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000666
25 distal amyotrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0003693
26 lower limb spasticity 59 32 occasional (7.5%) Occasional (29-5%) HP:0002061
27 ankle clonus 59 32 occasional (7.5%) Occasional (29-5%) HP:0011448
28 corpus callosum atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0007371
29 speech apraxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0011098
30 head tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0002346
31 hyperactive deep tendon reflexes 59 32 occasional (7.5%) Occasional (29-5%) HP:0006801
32 parietal cortical atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0012104
33 hypoplasia of the pons 59 32 occasional (7.5%) Occasional (29-5%) HP:0012110
34 gaze-evoked nystagmus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000640
35 hand tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0002378
36 spasticity 32 occasional (7.5%) HP:0001257
37 tremor 32 occasional (7.5%) HP:0001337
38 external ophthalmoplegia 32 occasional (7.5%) HP:0000544
39 hypothyroidism 59 32 very rare (1%) Very rare (<4-1%) HP:0000821
40 seizures 59 32 very rare (1%) Very rare (<4-1%) HP:0001250
41 type ii diabetes mellitus 59 32 very rare (1%) Very rare (<4-1%) HP:0005978
42 abnormal facial shape 59 32 very rare (1%) Very rare (<4-1%) HP:0001999
43 type i diabetes mellitus 59 32 very rare (1%) Very rare (<4-1%) HP:0100651
44 alopecia 59 32 very rare (1%) Very rare (<4-1%) HP:0001596
45 pancreatitis 59 32 very rare (1%) Very rare (<4-1%) HP:0001733
46 glaucoma 59 32 very rare (1%) Very rare (<4-1%) HP:0000501
47 saccadic smooth pursuit 59 32 very rare (1%) Very rare (<4-1%) HP:0001152
48 infertility 59 32 very rare (1%) Very rare (<4-1%) HP:0000789
49 oculomotor apraxia 59 32 very rare (1%) Very rare (<4-1%) HP:0000657
50 oligomenorrhea 59 32 very rare (1%) Very rare (<4-1%) HP:0000876

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
dysarthria
limb ataxia
cerebellar hypoplasia
truncal ataxia
cerebellar atrophy
more
Genitourinary Bladder:
urinary urge incontinence (in some patients)

Endocrine Features:
hypogonadotropic hypogonadism (in some females)
lack of secondary sexual characteristics (in 1 family)

Head And Neck Eyes:
nystagmus (in some patients)
external ophthalmoplegia (in some patients)

Neurologic Peripheral Nervous System:
sensory axonal neuropathy, distal, mild

Clinical features from OMIM:

615768

UMLS symptoms related to Spinocerebellar Ataxia, Autosomal Recessive 16:


ataxia, truncal

Drugs & Therapeutics for Spinocerebellar Ataxia, Autosomal Recessive 16

Search Clinical Trials , NIH Clinical Center for Spinocerebellar Ataxia, Autosomal Recessive 16

Genetic Tests for Spinocerebellar Ataxia, Autosomal Recessive 16

Genetic tests related to Spinocerebellar Ataxia, Autosomal Recessive 16:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia, Autosomal Recessive 16 29 STUB1

Anatomical Context for Spinocerebellar Ataxia, Autosomal Recessive 16

MalaCards organs/tissues related to Spinocerebellar Ataxia, Autosomal Recessive 16:

41
Eye, Spinal Cord, Cerebellum, Pons, Skeletal Muscle

Publications for Spinocerebellar Ataxia, Autosomal Recessive 16

Articles related to Spinocerebellar Ataxia, Autosomal Recessive 16:

(show all 16)
# Title Authors PMID Year
1
STUB1 mutations in autosomal recessive ataxias - evidence for mutation-specific clinical heterogeneity. 8 71
25258038 2014
2
Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts. 8 71
24742043 2014
3
Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP. 8 71
24113144 2014
4
Identification of CHIP as a novel causative gene for autosomal recessive cerebellar ataxia. 8 71
24312598 2013
5
Autosomal recessive cerebellar ataxia of adult onset due to STUB1 mutations. 8
24719489 2014
6
Feedback inhibition of cAMP effector signaling by a chaperone-assisted ubiquitin system. 38
31189917 2019
7
Spinocerebellar ataxia 48 presenting with ataxia associated with cognitive, psychiatric, and extrapyramidal features: A report of two Italian families. 38
31126790 2019
8
Generation of a homozygous CRISPR/Cas9-mediated knockout human iPSC line for the STUB1 locus. 38
30605842 2019
9
Inaugural cognitive decline, late disease onset and novel STUB1 variants in SCAR16. 38
30206723 2018
10
Heterozygous STUB1 mutation causes familial ataxia with cognitive affective syndrome (SCA48). 38
30381368 2018
11
STUB1 polyadenylation signal variant AACAAA does not affect polyadenylation but decreases STUB1 translation causing SCAR16. 38
30058754 2018
12
Disrupted structure and aberrant function of CHIP mediates the loss of motor and cognitive function in preclinical models of SCAR16. 38
30222779 2018
13
Establishment of STUB1/CHIP mutant induced pluripotent stem cells (iPSCs) from a patient with Gordon Holmes syndrome/SCAR16. 38
29679845 2018
14
Most mutations that cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16) destabilize the protein quality-control E3 ligase CHIP. 38
29317501 2018
15
In vitro characterization of six STUB1 variants in spinocerebellar ataxia 16 reveals altered structural properties for the encoded CHIP proteins. 38
28396517 2017
16
SKELETAL MUSCLE MITOCHONDRIAL ALTERATIONS IN CARBOXYL TERMINUS OF HSC70 INTERACTING PROTEIN (CHIP) -/- MICE. 38
28593200 2016

Variations for Spinocerebellar Ataxia, Autosomal Recessive 16

ClinVar genetic disease variations for Spinocerebellar Ataxia, Autosomal Recessive 16:

6 (show all 14)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 STUB1 NM_005861.4(STUB1): c.493C> T (p.Leu165Phe) single nucleotide variant Pathogenic rs587777340 16:731572-731572 16:681572-681572
2 STUB1 NM_005861.4(STUB1): c.389A> T (p.Asn130Ile) single nucleotide variant Pathogenic rs587777341 16:731468-731468 16:681468-681468
3 STUB1 NM_005861.4(STUB1): c.441G> T (p.Trp147Cys) single nucleotide variant Pathogenic rs587777342 16:731520-731520 16:681520-681520
4 STUB1 NM_005861.4(STUB1): c.737C> T (p.Thr246Met) single nucleotide variant Pathogenic rs587777343 16:732232-732232 16:682232-682232
5 STUB1 NM_005861.4(STUB1): c.367C> G (p.Leu123Val) single nucleotide variant Pathogenic rs587777344 16:731446-731446 16:681446-681446
6 STUB1 NM_005861.4(STUB1): c.719T> C (p.Met240Thr) single nucleotide variant Pathogenic rs587777345 16:732214-732214 16:682214-682214
7 STUB1 NM_005861.4(STUB1): c.235G> A (p.Ala79Thr) single nucleotide variant Pathogenic rs587777346 16:731227-731227 16:681227-681227
8 STUB1 NM_005861.4(STUB1): c.236C> A (p.Ala79Asp) single nucleotide variant Pathogenic rs587777347 16:731228-731228 16:681228-681228
9 STUB1 NM_005861.4(STUB1): c.194A> G (p.Asn65Ser) single nucleotide variant Pathogenic rs690016544 16:731186-731186 16:681186-681186
10 STUB1 NM_005861.4(STUB1): c.885dup (p.Glu296Ter) duplication Pathogenic 16:732462-732463 16:682462-682462
11 STUB1 NM_005861.4(STUB1): c.646dup (p.Ser216fs) duplication Pathogenic rs1555475283 16:732053-732053 16:682053-682053
12 STUB1 NM_005861.4(STUB1): c.694_699del (p.Cys232_Gly233del) deletion Likely pathogenic rs1555475375 16:732189-732194 16:682189-682194
13 STUB1 NM_005861.4(STUB1): c.721C> G (p.Arg241Gly) single nucleotide variant Likely pathogenic rs760424025 16:732216-732216 16:682216-682216
14 STUB1 NM_005861.4(STUB1): c.*240T> C single nucleotide variant Likely pathogenic rs1555475794 16:732729-732729 16:682729-682729

UniProtKB/Swiss-Prot genetic disease variations for Spinocerebellar Ataxia, Autosomal Recessive 16:

74 (show all 12)
# Symbol AA change Variation ID SNP ID
1 STUB1 p.Ala79Asp VAR_071293 rs587777347
2 STUB1 p.Ala79Thr VAR_071294 rs587777346
3 STUB1 p.Leu123Val VAR_071295 rs587777344
4 STUB1 p.Asn130Ile VAR_071296 rs587777341
5 STUB1 p.Trp147Cys VAR_071297 rs587777342
6 STUB1 p.Leu165Phe VAR_071298 rs587777340
7 STUB1 p.Ser236Thr VAR_071299
8 STUB1 p.Met240Thr VAR_071300 rs587777345
9 STUB1 p.Thr246Met VAR_071301 rs587777343
10 STUB1 p.Glu28Lys VAR_072348
11 STUB1 p.Asn65Ser VAR_072349 rs690016544
12 STUB1 p.Lys145Gln VAR_072350 rs146251364

Expression for Spinocerebellar Ataxia, Autosomal Recessive 16

Search GEO for disease gene expression data for Spinocerebellar Ataxia, Autosomal Recessive 16.

Pathways for Spinocerebellar Ataxia, Autosomal Recessive 16

Pathways related to Spinocerebellar Ataxia, Autosomal Recessive 16 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.86 STUB1 HSPA4
2
Show member pathways
11.31 STUB1 HSPA4
3
Show member pathways
10.96 STUB1 HSPA4
4 10.17 STUB1 HSPA4

GO Terms for Spinocerebellar Ataxia, Autosomal Recessive 16

Sources for Spinocerebellar Ataxia, Autosomal Recessive 16

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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