SCAR16
MCID: SPN273
MIFTS: 44

Spinocerebellar Ataxia, Autosomal Recessive 16 (SCAR16)

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 16

MalaCards integrated aliases for Spinocerebellar Ataxia, Autosomal Recessive 16:

Name: Spinocerebellar Ataxia, Autosomal Recessive 16 56 29 6 71
Scar16 56 58 73
Autosomal Recessive Spinocerebellar Ataxia 16 12 15
Autosomal Recessive Cerebellar Ataxia Due to Stub1 Deficiency 58
Ataxia, Spinocerebellar, Autosomal Recessive, Type 16 39
Spinocerebellar Ataxia Autosomal Recessive Type 16 58
Spinocerebellar Ataxia, Autosomal Recessive, 16 73

Characteristics:

Orphanet epidemiological data:

58
autosomal recessive cerebellar ataxia due to stub1 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

56
Inheritance:
autosomal recessive

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


HPO:

31
spinocerebellar ataxia, autosomal recessive 16:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Spinocerebellar Ataxia, Autosomal Recessive 16

UniProtKB/Swiss-Prot : 73 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 Parathyroid hormone synthesis, secretion and action and Pancreatic secretion. Affiliated tissues include eye, cerebellum and spinal cord, and related phenotypes are dysarthria and limb ataxia

OMIM : 56 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 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 Type 19/22 Grid2-Related Spinocerebellar Ataxia
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
4 spinocerebellar ataxia 48 9.9 STUB1 JMJD8
5 spinal and bulbar muscular atrophy, x-linked 1 9.6 STUB1 ST13
6 cutaneous anthrax 9.5 ADCY2 ADCY1

Graphical network of the top 20 diseases related to Spinocerebellar Ataxia, Autosomal Recessive 16:



Diseases related to Spinocerebellar Ataxia, Autosomal Recessive 16

Symptoms & Phenotypes for Spinocerebellar Ataxia, Autosomal Recessive 16

Human phenotypes related to Spinocerebellar Ataxia, Autosomal Recessive 16:

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

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
dysarthria
limb ataxia
cerebellar hypoplasia
truncal ataxia
cerebellar atrophy
more
Genitourinary Bladder:
urinary urgency (in some patients)
urinary 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:

40
Eye, Cerebellum, Spinal Cord, Pons, Skeletal Muscle, Liver, Skin

Publications for Spinocerebellar Ataxia, Autosomal Recessive 16

Articles related to Spinocerebellar Ataxia, Autosomal Recessive 16:

(show all 19)
# Title Authors PMID Year
1
STUB1 mutations in autosomal recessive ataxias - evidence for mutation-specific clinical heterogeneity. 56 6
25258038 2014
2
Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts. 56 6
24742043 2014
3
Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP. 56 6
24113144 2014
4
Identification of CHIP as a novel causative gene for autosomal recessive cerebellar ataxia. 56 6
24312598 2013
5
Autosomal recessive cerebellar ataxia of adult onset due to STUB1 mutations. 56
24719489 2014
6
The complex phenotype of spinocerebellar ataxia type 48 in eight unrelated Italian families. 61
31571321 2020
7
Changes in protein function underlie the disease spectrum in patients with CHIP mutations. 61
31619515 2019
8
Spinocerebellar ataxia 48 presenting with ataxia associated with cognitive, psychiatric, and extrapyramidal features: A report of two Italian families. 61
31126790 2019
9
Feedback inhibition of cAMP effector signaling by a chaperone-assisted ubiquitin system. 61
31189917 2019
10
[Diagnostic algorithm for autosomal recessive ataxia]. 61
31626222 2019
11
Generation of a homozygous CRISPR/Cas9-mediated knockout human iPSC line for the STUB1 locus. 61
30605842 2019
12
Inaugural cognitive decline, late disease onset and novel STUB1 variants in SCAR16. 61
30206723 2018
13
Heterozygous STUB1 mutation causes familial ataxia with cognitive affective syndrome (SCA48). 61
30381368 2018
14
STUB1 polyadenylation signal variant AACAAA does not affect polyadenylation but decreases STUB1 translation causing SCAR16. 61
30058754 2018
15
Disrupted structure and aberrant function of CHIP mediates the loss of motor and cognitive function in preclinical models of SCAR16. 61
30222779 2018
16
Establishment of STUB1/CHIP mutant induced pluripotent stem cells (iPSCs) from a patient with Gordon Holmes syndrome/SCAR16. 61
29679845 2018
17
Most mutations that cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16) destabilize the protein quality-control E3 ligase CHIP. 61
29317501 2018
18
In vitro characterization of six STUB1 variants in spinocerebellar ataxia 16 reveals altered structural properties for the encoded CHIP proteins. 61
28396517 2017
19
SKELETAL MUSCLE MITOCHONDRIAL ALTERATIONS IN CARBOXYL TERMINUS OF HSC70 INTERACTING PROTEIN (CHIP) -/- MICE. 61
28593200 2016

Variations for Spinocerebellar Ataxia, Autosomal Recessive 16

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

6 (show all 15) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 STUB1 NM_005861.4(STUB1):c.367C>G (p.Leu123Val)SNV Pathogenic 127147 rs587777344 16:731446-731446 16:681446-681446
2 STUB1 NM_005861.4(STUB1):c.719T>C (p.Met240Thr)SNV Pathogenic 127148 rs587777345 16:732214-732214 16:682214-682214
3 STUB1 NM_005861.4(STUB1):c.235G>A (p.Ala79Thr)SNV Pathogenic 127149 rs587777346 16:731227-731227 16:681227-681227
4 STUB1 NM_005861.4(STUB1):c.236C>A (p.Ala79Asp)SNV Pathogenic 127150 rs587777347 16:731228-731228 16:681228-681228
5 STUB1 NM_005861.4(STUB1):c.646dup (p.Ser216fs)duplication Pathogenic 436887 rs1555475283 16:732047-732048 16:682047-682048
6 STUB1 NM_005861.4(STUB1):c.493C>T (p.Leu165Phe)SNV Pathogenic 127143 rs587777340 16:731572-731572 16:681572-681572
7 STUB1 NM_005861.4(STUB1):c.389A>T (p.Asn130Ile)SNV Pathogenic 127144 rs587777341 16:731468-731468 16:681468-681468
8 STUB1 NM_005861.4(STUB1):c.441G>T (p.Trp147Cys)SNV Pathogenic 127145 rs587777342 16:731520-731520 16:681520-681520
9 STUB1 NM_005861.4(STUB1):c.194A>G (p.Asn65Ser)SNV Pathogenic 162097 rs690016544 16:731186-731186 16:681186-681186
10 STUB1 NM_005861.4(STUB1):c.885dup (p.Glu296Ter)duplication Pathogenic 623185 rs1567283195 16:732461-732462 16:682461-682462
11 STUB1 NM_005861.4(STUB1):c.694_699del (p.Cys232_Gly233del)deletion Likely pathogenic 436888 rs1555475375 16:732189-732194 16:682189-682194
12 STUB1 NM_005861.4(STUB1):c.721C>G (p.Arg241Gly)SNV Likely pathogenic 436889 rs760424025 16:732216-732216 16:682216-682216
13 STUB1 NM_005861.4(STUB1):c.*240T>CSNV Likely pathogenic 522378 rs1555475794 16:732729-732729 16:682729-682729
14 STUB1 NM_005861.4(STUB1):c.433A>C (p.Lys145Gln)SNV Uncertain significance 212325 rs146251364 16:731512-731512 16:681512-681512
15 STUB1 NM_005861.4(STUB1):c.737C>T (p.Thr246Met)SNV Uncertain significance 127146 rs587777343 16:732232-732232 16:682232-682232

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

73 (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

GO Terms for Spinocerebellar Ataxia, Autosomal Recessive 16

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

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0007189 9.51 ADCY2 ADCY1
2 positive regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0032436 9.49 STUB1 HSPBP1
3 positive regulation of protein ubiquitination GO:0031398 9.48 STUB1 HSPBP1
4 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway GO:0007193 9.46 ADCY2 ADCY1
5 activation of adenylate cyclase activity GO:0007190 9.43 ADCY2 ADCY1
6 renal water homeostasis GO:0003091 9.4 ADCY2 ADCY1
7 cAMP-mediated signaling GO:0019933 9.37 ADCY2 ADCY1
8 cellular response to glucagon stimulus GO:0071377 9.32 ADCY2 ADCY1
9 activation of protein kinase A activity GO:0034199 9.26 ADCY2 ADCY1
10 cyclic nucleotide biosynthetic process GO:0009190 9.16 ADCY2 ADCY1
11 cellular response to forskolin GO:1904322 8.96 ADCY2 ADCY1
12 cAMP biosynthetic process GO:0006171 8.62 ADCY2 ADCY1

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

# Name GO ID Score Top Affiliating Genes
1 chaperone binding GO:0051087 9.32 STUB1 ST13
2 protein binding, bridging GO:0030674 9.26 STUB1 ST13
3 Hsp70 protein binding GO:0030544 9.16 STUB1 ST13
4 phosphorus-oxygen lyase activity GO:0016849 8.96 ADCY2 ADCY1
5 adenylate cyclase activity GO:0004016 8.62 ADCY2 ADCY1

Sources for Spinocerebellar Ataxia, Autosomal Recessive 16

3 CDC
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11 DGIdb
17 EFO
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68 SNOMED-CT via HPO
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