Spinocerebellar Ataxia 36 (NOP56)
| Dred_ID | RD00055 |
| OMIM ID | 614153 |
| Disease name | Spinocerebellar Ataxia 36 |
| Alternative names | Asidan/SCA36, Costa da Morte Ataxia, SCA36 |
| Category | Genetic diseases, Rare diseases, Neuronal diseases, Skin diseases, Eye diseases, Mental diseases, Ear diseases, Metabolic diseases, Fetal diseases, Liver diseases |
| Phenotype | OMIM: Spinocerebellar ataxia type 36 (SCA36) is characterized by a late-onset, slowly progressive cerebellar syndrome typically associated with sensorineural hearing loss. Other common features are muscle atrophy and denervation, especially of the tongue, as well as pyramidal signs, thus overlapping with motor neuron disorders. Mild frontal-subcortical affective and cognitive decline may be present as the disease progresses. Brain MRI shows atrophy of the cerebellar vermis in initial stages, later evolving to a pattern of olivopontocerebellar atrophy. Confirmation of the diagnosis relies on detection of an abnormal hexanucleotide GGCCTG repeat expansion in NOP56. Affected individuals typically have alleles with 650 or more repeats. Such testing detects virtually 100% of affected individuals. |
| Miscellaneouse | OMIM: progressive disorder mean age at onset of cerebellar ataxia is 52.8 years patients with longer disease duration show motor neuron involvement described in families from western japan described in families from galicia, spain unaffected individuals carry 3 to 14 repeats, whereas affected individuals carry 650 to 2,500 repeats |
| Prevalence | Prevalence: <1/1000000 (Worldwide); [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | NOP56 |
| Alias symbols | NOL5A; SCA36 |
| Gene name | NOP56 ribonucleoprotein |
| Gene map locus | 20p13; chr20:2,652,593-2,658,393(+) |
| Ensembl Gene ID | ENSG00000101361 |
| 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 | Nop56p is a yeast nucleolar protein that is part of a complex with the nucleolar proteins Nop58p and fibrillarin. Nop56p is required for assembly of the 60S ribosomal subunit and is involved in pre-rRNA processing. The protein encoded by this gene is similar in sequence to Nop56p and is also found in the nucleolus. Expansion of a GGCCTG repeat from 3-8 copies to 1500-2500 copies in an intron of this gene results in spinocerebellar ataxia 36. Multiple transcript variants encoding several different isoforms have been found for this gene, but the full-length nature of most of them has not been determined. [provided by RefSeq, Jul 2016] |
| Repeat unit | GGCCTG |
| Normal repeat copies | 3-14 |
| Pathogenic repeat copies | ≥650 |
| Gene | NOP56 |
| Repeat location | intron |
| Chromosome locus | chr20:2652734-2652760 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | In total, nine unrelated cases were found in 251 cohort SCA patients (3.6%). A founder haplotype was confirmed in these cases. RNA foci formation was detected in lymphoblastoid cells from affected subjects by fluorescence in situ hybridization. Double staining and gel-shift assay showed that (GGCCUG)n binds the RNA-binding protein SRSF2 but that (CUG)(6) does not. In addition, transcription of MIR1292, a neighboring miRNA, was significantly decreased in lymphoblastoid cells of SCA patients. Our finding suggests that SCA36 is caused by hexanucleotide repeat expansions through RNA gain of function. [By PMID: 21683323] |
| Pathway annotation | Reactome, KEGG |
| PMID | 21683323 |
| Authors | Kobayashi H, Abe K, Matsuura T, Ikeda Y, Hitomi T, Akechi Y, Habu T, Liu W, Okuda H, Koizumi A |
| Title | Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement |
| Journal | Am J Hum Genet. 89(1):121-30 |
| Year | 2011 |