SCA35
MCID: SPN266
MIFTS: 34

Spinocerebellar Ataxia 35 (SCA35)

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 35

MalaCards integrated aliases for Spinocerebellar Ataxia 35:

Name: Spinocerebellar Ataxia 35 58 54 76 30 13 6 74
Sca35 58 54 60 76
Spinocerebellar Ataxia Type 35 12 60 15
Ataxia, Spinocerebellar, Type 35 41

Characteristics:

Orphanet epidemiological data:

60
spinocerebellar ataxia type 35
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
variable age at onset (range teenage to adult years)


HPO:

33
spinocerebellar ataxia 35:
Onset and clinical course adult onset slow progression
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Spinocerebellar Ataxia 35

UniProtKB/Swiss-Prot : 76 Spinocerebellar ataxia 35: 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. SCA35 patients commonly show upper limb involvement and torticollis. There is no cognitive impairment.

MalaCards based summary : Spinocerebellar Ataxia 35, also known as sca35, is related to ataxia and polyneuropathy, adult-onset and autosomal dominant cerebellar ataxia, and has symptoms including action tremor and abnormal pyramidal signs. An important gene associated with Spinocerebellar Ataxia 35 is TGM6 (Transglutaminase 6). Affiliated tissues include eye, spinal cord and cerebellum, and related phenotypes are progressive cerebellar ataxia and hyperreflexia

Disease Ontology : 12 An autosomal dominant cerebellar ataxia that is characterized by a slowly progressive ataxia, tremor, dysarthria and hyperreflexia, has material basis in mutation in the TGM6 gene.

OMIM : 58 Spinocerebellar ataxia-35 is an autosomal dominant adult-onset neurologic disorder characterized by difficulty walking due to cerebellar ataxia. The age at onset ranges from teenage years to late adulthood, and the disorder is slowly progressive. Additional features may include hand tremor, dysarthria, hyperreflexia, and saccadic eye movements (summary by Guo et al., 2014). (613908)

Related Diseases for Spinocerebellar Ataxia 35

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 Grid2-Related Spinocerebellar Ataxia
Spinocerebellar Ataxia Autosomal Recessive 5

Diseases related to Spinocerebellar Ataxia 35 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 ataxia and polyneuropathy, adult-onset 10.1
2 autosomal dominant cerebellar ataxia 10.1
3 autoimmune disease of gastrointestinal tract 9.6 TGM2 TGM6
4 dermatitis herpetiformis 9.5 TGM2 TGM6

Symptoms & Phenotypes for Spinocerebellar Ataxia 35

Human phenotypes related to Spinocerebellar Ataxia 35:

60 33 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 progressive cerebellar ataxia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002073
2 hyperreflexia 60 33 frequent (33%) Frequent (79-30%) HP:0001347
3 gait ataxia 60 33 frequent (33%) Frequent (79-30%) HP:0002066
4 limb ataxia 60 33 frequent (33%) Frequent (79-30%) HP:0002070
5 babinski sign 60 33 frequent (33%) Frequent (79-30%) HP:0003487
6 dysmetria 60 33 frequent (33%) Frequent (79-30%) HP:0001310
7 intention tremor 60 33 frequent (33%) Frequent (79-30%) HP:0002080
8 difficulty walking 60 33 frequent (33%) Frequent (79-30%) HP:0002355
9 cerebellar atrophy 60 33 frequent (33%) Frequent (79-30%) HP:0001272
10 intellectual disability, moderate 60 33 occasional (7.5%) Occasional (29-5%) HP:0002342
11 torticollis 60 33 occasional (7.5%) Occasional (29-5%) HP:0000473
12 neck muscle weakness 60 33 occasional (7.5%) Occasional (29-5%) HP:0000467
13 dysmetric saccades 60 33 occasional (7.5%) Occasional (29-5%) HP:0000641
14 pseudobulbar paralysis 60 33 occasional (7.5%) Occasional (29-5%) HP:0007024
15 dysarthria 60 33 Frequent (79-30%) HP:0001260
16 nystagmus 60 Excluded (0%)
17 peripheral neuropathy 60 Excluded (0%)
18 ophthalmoplegia 60 Excluded (0%)
19 incoordination 33 HP:0002311
20 abnormality of the orbital region 33 HP:0000315

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
dysarthria
hyperreflexia
dysmetria
intention tremor
difficulty walking
more
Head And Neck Neck:
torticollis (rare)
neck muscle weakness (rare)

Head And Neck Eyes:
ocular dysmetria
saccadic slowing

Clinical features from OMIM:

613908

UMLS symptoms related to Spinocerebellar Ataxia 35:


action tremor, abnormal pyramidal signs

Drugs & Therapeutics for Spinocerebellar Ataxia 35

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Spinocerebellar Ataxia 35

Genetic Tests for Spinocerebellar Ataxia 35

Genetic tests related to Spinocerebellar Ataxia 35:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia 35 30 TGM6

Anatomical Context for Spinocerebellar Ataxia 35

MalaCards organs/tissues related to Spinocerebellar Ataxia 35:

42
Eye, Spinal Cord, Cerebellum, Brain, Skin, Liver

Publications for Spinocerebellar Ataxia 35

Articles related to Spinocerebellar Ataxia 35:

# Title Authors Year
1
Hispanic Spinocerebellar Ataxia Type 35 (SCA35) with a Novel Frameshift Mutation. ( 30229425 )
2019
2
Mutations in TGM6 induce the unfolded protein response in SCA35. ( 28934387 )
2017
3
Spinocerebellar ataxia 35: novel mutations in TGM6 with clinical and genetic characterization. ( 25253745 )
2014
4
Spinocerebellar ataxia type 35 (SCA35)-associated transglutaminase 6 mutants sensitize cells to apoptosis. ( 23206699 )
2013
5
Whole exome sequencing identifies a novel mutation in the transglutaminase 6 gene for spinocerebellar ataxia in a Chinese family. ( 22554020 )
2013
6
TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. ( 21106500 )
2010

Variations for Spinocerebellar Ataxia 35

UniProtKB/Swiss-Prot genetic disease variations for Spinocerebellar Ataxia 35:

76
# Symbol AA change Variation ID SNP ID
1 TGM6 p.Asp327Gly VAR_065360 rs387907098
2 TGM6 p.Leu517Trp VAR_065361 rs387907097
3 TGM6 p.Arg111Cys VAR_072179 rs372250159
4 TGM6 p.Asp510His VAR_072180 rs201964784
5 TGM6 p.Thr426Asn VAR_080737

ClinVar genetic disease variations for Spinocerebellar Ataxia 35:

6 (show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 TGM6 NM_198994.2(TGM6): c.1550T> G (p.Leu517Trp) single nucleotide variant Pathogenic rs387907097 GRCh37 Chromosome 20, 2398091: 2398091
2 TGM6 NM_198994.2(TGM6): c.1550T> G (p.Leu517Trp) single nucleotide variant Pathogenic rs387907097 GRCh38 Chromosome 20, 2417445: 2417445
3 TGM6 NM_198994.2(TGM6): c.980A> G (p.Asp327Gly) single nucleotide variant Pathogenic rs387907098 GRCh37 Chromosome 20, 2381081: 2381081
4 TGM6 NM_198994.2(TGM6): c.980A> G (p.Asp327Gly) single nucleotide variant Pathogenic rs387907098 GRCh38 Chromosome 20, 2400435: 2400435
5 TGM6 NM_198994.2(TGM6): c.1528G> C (p.Asp510His) single nucleotide variant Pathogenic rs201964784 GRCh37 Chromosome 20, 2398069: 2398069
6 TGM6 NM_198994.2(TGM6): c.1528G> C (p.Asp510His) single nucleotide variant Pathogenic rs201964784 GRCh38 Chromosome 20, 2417423: 2417423
7 TGM6 NM_198994.2(TGM6): c.1476G> A (p.Lys492=) single nucleotide variant Benign rs2295077 GRCh37 Chromosome 20, 2398017: 2398017
8 TGM6 NM_198994.2(TGM6): c.1476G> A (p.Lys492=) single nucleotide variant Benign rs2295077 GRCh38 Chromosome 20, 2417371: 2417371
9 TGM6 NM_198994.2(TGM6): c.172A> G (p.Met58Val) single nucleotide variant Benign rs2076405 GRCh37 Chromosome 20, 2375262: 2375262
10 TGM6 NM_198994.2(TGM6): c.172A> G (p.Met58Val) single nucleotide variant Benign rs2076405 GRCh38 Chromosome 20, 2394616: 2394616
11 TGM6 NM_198994.2(TGM6): c.331C> T (p.Arg111Cys) single nucleotide variant Pathogenic rs372250159 GRCh38 Chromosome 20, 2395343: 2395343
12 TGM6 NM_198994.2(TGM6): c.331C> T (p.Arg111Cys) single nucleotide variant Pathogenic rs372250159 GRCh37 Chromosome 20, 2375989: 2375989
13 TGM6 NM_198994.2(TGM6): c.1722_1724delAGA (p.Glu574del) deletion Pathogenic rs793888526 GRCh37 Chromosome 20, 2411135: 2411137
14 TGM6 NM_198994.2(TGM6): c.1722_1724delAGA (p.Glu574del) deletion Pathogenic rs793888526 GRCh38 Chromosome 20, 2430489: 2430491
15 TGM6 NM_198994.2(TGM6): c.850+12G> A single nucleotide variant Benign rs2076404 GRCh37 Chromosome 20, 2380396: 2380396
16 TGM6 NM_198994.2(TGM6): c.850+12G> A single nucleotide variant Benign rs2076404 GRCh38 Chromosome 20, 2399750: 2399750
17 TGM6 NM_198994.2(TGM6): c.1968-11C> T single nucleotide variant Benign rs2076653 GRCh38 Chromosome 20, 2432479: 2432479
18 TGM6 NM_198994.2(TGM6): c.1968-11C> T single nucleotide variant Benign rs2076653 GRCh37 Chromosome 20, 2413125: 2413125
19 TGM6 NM_198994.2(TGM6): c.1968-10C> T single nucleotide variant Benign rs6036467 GRCh38 Chromosome 20, 2432480: 2432480
20 TGM6 NM_198994.2(TGM6): c.1968-10C> T single nucleotide variant Benign rs6036467 GRCh37 Chromosome 20, 2413126: 2413126

Expression for Spinocerebellar Ataxia 35

Search GEO for disease gene expression data for Spinocerebellar Ataxia 35.

Pathways for Spinocerebellar Ataxia 35

GO Terms for Spinocerebellar Ataxia 35

Biological processes related to Spinocerebellar Ataxia 35 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peptide cross-linking GO:0018149 8.62 TGM2 TGM6

Molecular functions related to Spinocerebellar Ataxia 35 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity, transferring acyl groups GO:0016746 8.96 TGM2 TGM6
2 protein-glutamine gamma-glutamyltransferase activity GO:0003810 8.62 TGM2 TGM6

Sources for Spinocerebellar Ataxia 35

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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