{"doi":"10.1093/hmg/9.12.1753","title":"CAG repeat length in RAI1 is associated with age at onset variability in spinocerebellar ataxia type 2 (SCA2)","abstract":null,"journal":"Human Molecular Genetics","year":2000,"id":636887,"datarank":0.6749714505495399,"base_score":4.499809670330265,"endowment":4.499809670330265,"self_citation_contribution":0.6749714505495399,"citation_network_contribution":0.0,"self_endowment_contribution":0.6749714505495399,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":89,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1629591,"name":"S. Hayes","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"CAG repeat length in RAI1 is associated with age at onset variability in spinocerebellar ataxia type 2 (SCA2)","abstract":"Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder caused by the expansion of a polymorphic (CAG)(n) tract, which is translated into an expanded polyglutamine tract in the ataxin-2 protein. Although repeat length and age at disease onset are inversely related, approximately 50% of the age at onset variance in SCA2 remains unexplained. Other familial factors have been proposed to account for at least part of this remaining variance in the polyglutamine dis-orders. The ability of polyglutamine tracts to interact with each other, as well as the presence of intra-nuclear inclusions in other polyglutamine disorders, led us to hypothesize that other CAG-containing proteins may interact with expanded ataxin-2 and affect the rate of protein accumulation, and thus influence age at onset. To test this hypothesis, we used step-wise multiple linear regression to examine 10 CAG-containing genes for possible influences on SCA2 age at onset. One locus, RAI1, contributed an additional 4.1% of the variance in SCA2 age at onset after accounting for the effect of the SCA2 expanded repeat. This locus was further studied in SCA3/Machado-Joseph disease (MJD), but did not have an effect on SCA3/MJD age at onset. This result implicates RAI1 as a possible contributor to SCA2 neurodegeneration and raises the possibility that other CAG-containing proteins may play a role in the pathogenesis of other polyglutamine disorders.","is_dataset_classified":null,"base_score":4.499809670330265,"endowment":4.499809670330265,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10915763","pmcid":null,"openalex_id":"https://openalex.org/W2119887971","authors":[],"funders":[],"total_grants":0,"fwci":1.0955,"citation_percentile":0.74139626,"influential_citations":4,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":6},{"year":2014,"count":5},{"year":2015,"count":2},{"year":2016,"count":3},{"year":2017,"count":8},{"year":2018,"count":4},{"year":2019,"count":3},{"year":2021,"count":2},{"year":2022,"count":4},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/hmg/article-pdf/9/12/1753/9813764/091753.pdf","host_type":"journal"},{"url":"https://academic.oup.com/hmg/article-pdf/9/12/1753/9813764/091753.pdf","host_type":"BRONZE"},{"url":"https://academic.oup.com/hmg/article-pdf/9/12/1753/9813764/091753.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/hmg/article-pdf/9/12/1753/9813764/091753.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/hmg/9.12.1753","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10915763","host_type":"repository"}],"fields_of_study":["Genetic Neurodegenerative Diseases","Mitochondrial Function and Pathology","Neurological disorders and treatments","Biology","Medicine","Age of Onset","Alleles","Ataxins","Humans","Nerve Tissue Proteins","Potassium Channels","Potassium Channels, Calcium-Activated","Proteins","Small-Conductance Calcium-Activated Potassium Channels","Spinocerebellar Ataxias","Trinucleotide Repeats"],"mesh_terms":["Ataxins","Alleles","Humans","Nerve Tissue Proteins","Proteins","Potassium Channels","Age of Onset","Trinucleotide Repeats","Spinocerebellar Ataxias","Potassium Channels, Calcium-Activated","Small-Conductance Calcium-Activated Potassium Channels"],"keywords":["Machado–Joseph disease","Spinocerebellar ataxia","Polyglutamine tract","Biology","Trinucleotide repeat expansion","Locus (genetics)","Age of onset","Neurodegeneration","Ataxia","Genetics","Degenerative disease","Disease","Central nervous system disease","Gene","Neuroscience","Internal medicine","Allele","Medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T17:54:50.686268Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}