Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome (RFC1)
| Dred_ID | RD00048 |
| OMIM ID | 614575 |
| Disease name | Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome |
| Alternative names | CANVAS |
| Category | Genetic diseases, Neuronal diseases |
| Phenotype | OMIM: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive adult-onset, slowly progressive neurologic disorder characterized by imbalance due to cerebellar gait and limb ataxia, impaired vestibular function bilaterally, and non-length-dependent sensory neuropathy (summary by Szmulewicz et al., 2011). |
| Miscellaneouse | Slowly progressive Adult onset (mean 54 years) |
| Prevalence | <1/1000000 (Worldwide) [source: MalaCards] |
| Inheritance | Autosomal recessive |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | RFC1 |
| Alias symbols | A1; RFC; PO-GA; RECC1; CANVAS; MHCBFB; RFC140 |
| Gene name | replication factor C subunit 1 |
| Gene map locus | 4p14; chr4:39,287,456-39,366,381(-) |
| Ensembl Gene ID | ENSG00000035928 |
| 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 | This gene encodes the large subunit of replication factor C, a five subunit DNA polymerase accessory protein, which is a DNA-dependent ATPase required for eukaryotic DNA replication and repair. The large subunit acts as an activator of DNA polymerases, binds to the 3' end of primers, and promotes coordinated synthesis of both strands. It may also have a role in telomere stability. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. |
| Repeat unit | AAGGG |
| Normal repeat copies | 11 |
| Pathogenic repeat copies | ≥100 |
| Gene | RFC1 |
| Repeat location | intron |
| Chromosome locus | NULL (-) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive adult-onset, slowly progressive neurologic disorder characterized by imbalance due to cerebellar gait and limb ataxia, impaired vestibular function bilaterally, and non-length-dependent sensory neuropathy. |
| Pathway annotation | Reactome, KEGG |
| PMID | 32040556 |
| Authors | Paisán-Ruiz C, Jen JC. |
| Title | CANVAS with cerebellar/sensory/vestibular dysfunction from RFC1 intronic pentanucleotide expansion |
| Journal | Brain |
| Year | 2020 |
| PMID | 32040556 |
| Authors | Cortese A, Tozza S, Yau WY, Rossi S, et al |
| Title | Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion |
| Journal | Brain |
| Year | 2020 |