Spinocerebellar Ataxia 7 (ATXN7)
| Dred_ID | RD00005 |
| OMIM ID | 164500 |
| Disease name | Spinocerebellar Ataxia 7 |
| Alternative names | SCA7 |
| Category | Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Skin diseases, Mental diseases, Ear diseases, Metabolic diseases, Fetal diseases, Liver diseases |
| Phenotype | pinocerebellar ataxia type 7 (SCA7) is characterized by progressive cerebellar ataxia, including dysarthria and dysphagia, and cone-rod and retinal dystrophy with progressive central visual loss resulting in blindness in affected adults. Onset in early childhood or infancy has an especially rapid and aggressive course often associated with failure to thrive and regression of motor milestones. |
| Miscellaneouse | OMIM: genetic anticipation paternal anticipation bias mean age at onset 32 years |
| Prevalence | Prevalence: 1-9/1000000 (Worldwide) [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | ATXN7 |
| Alias symbols | SCA7; OPCA3; ADCAII |
| Gene name | ataxin 7 |
| Gene map locus | 3p14.1; chr3:63,863,144-64,003,462(+) |
| Ensembl Gene ID | ENSG00000163635 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the 'pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. This locus has been mapped to chromosome 3, and it has been determined that the diseased allele associated with spinocerebellar ataxia-7 contains 37-306 CAG repeats (near the N-terminus), compared to 4-35 in the normal allele. The encoded protein is a component of the SPT3/TAF9/GCN5 acetyltransferase (STAGA) and TBP-free TAF-containing (TFTC) chromatin remodeling complexes, and it thus plays a role in transcriptional regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016] |
| Repeat unit | CAG |
| Normal repeat copies | 4-28 |
| Pathogenic repeat copies | ≥37 |
| Gene | ATXN7 |
| Repeat location | CDS |
| Chromosome locus | chr3:63912686-63912718 (-) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | Protein |
| Possible toxicity | The SCA7 protein ATXN7 is a component of the SPT–ADA–GCN5 acetyltransferase complex (SAGA complex)106. SAGA broadly regulates transcription through its dual histone-modifying enzymes, the histone acetyltransferase GCN5 (also known as KAT2A) and the DUB ubiquitin C-terminal hydrolase 22 (USP22). Although ATXN7 itself has no enzymatic activity, it anchors USP22 within the DUB module of the SAGA complex, enhancing the DUB activity of SAGA. In vitro, normal and polyQ-expanded ATXN7 enhance DUB activity equally; however, in vivo, expanded ATXN7 forms insoluble complexes that sequester other components of the DUB module such that the SAGA complex can no longer remove ubiquitin from its substrates, including histone H2B107. This dominant-negative effect of expanded ATXN7 probably disrupts the careful balance between the acetylation and de-ubiquitylation mediated by SAGA, leading to deleterious changes in gene expression that help to precipitate retinal and neurodegeneration in SCA7. [By PMID: 28855740] |
| Pathway annotation | Reactome, KEGG |
| PMID | 23100044 |
| Authors | van der Heijden CD, Rijpkema M, Arias-Vásquez A, Hakobjan M, Scheffer H, Fernandez G, Franke B, van de Warrenburg BP |
| Title | Genetic variation in ataxia gene ATXN7 influences cerebellar grey matter volume in healthy adults |
| Journal | Cerebellum. 12(3):390-5 |
| Year | 2013 |
| PMID | 16434483 |
| Authors | Abou-Sleymane G, Chalmel F, Helmlinger D, Lardenois A, Thibault C, Weber C, Mérienne K, Mandel JL, Poch O, Devys D, Trottier Y |
| Title | Polyglutamine expansion causes neurodegeneration by altering the neuronal differentiation program |
| Journal | Hum Mol Genet. 15(5):691-703 |
| Year | 2006 |