SCA31_BEAN1
- Gene
- BEAN1
- Disease
- SCA31
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 12
- Publications Reviewed
- 4
- Publication Span
- 13.33 years
- Last Updated
- 08/11/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
SCA31 is an autosomal dominant, late-onset progressive cerebellar ataxia associated with a 2.5–3.8 kb complex pentanucleotide repeat insertion containing pathogenic (TGGAA)n at the shared intronic BEAN1/TK2 locus. The insertion was reported in 160 affected individuals from 98 SCA31 families, was absent from disease controls and SCA4 subjects, and rare control insertions were shorter and lacked the (TGGAA)n component. Repeat insertion length inversely correlates with age at onset, and patient Purkinje cells show sense-direction RNA foci, supporting a toxic RNA gain-of-function mechanism. The locus-disease relationship is classified as Definitive.
Genetic evidence
Total: 9
| Singular Evidence | Probands | PMID:19878914 | 6 | The pathogenic 2.5–3.8 kb BEAN1/TK2 intronic repeat insertion containing (TGGAA)n was identified in 160 affected individuals from 98 SCA31 families. |
| Collective Evidence | Allele | PMID:19878914 | 1 | Insertion length inversely correlated with age at onset (r = -0.41, p = 0.010, n = 39), with subtle expansion documented in one family showing mild anticipation. |
| Statistics | Case-control data | PMID:19878914 | 2 | The SCA31 insertion was found in affected individuals and was absent from 21 disease controls and SCA4 subjects; 2/860 control chromosomes carried shorter insertions lacking (TGGAA)n and were considered non-pathogenic. |
Experimental evidence
Total: 3
| Function | Biochemical function | PMID:36371266 | 0.5 | BEAN1 (TGGAA)n repeat is transcribed to (UGGAA)n RNA that forms RNA foci in Purkinje cells and binds TDP-43, FUS, and hnRNP A2/B1. |
| Function | Protein interaction | PMID:36563608 | 0.5 | Review-level, locus-specific evidence: TDP-43 is described as suppressing (UGGAA)n-mediated neurotoxicity; original interaction experiments are cited within the review but not presented in this source. |
| Function | Regulatory impact | PMID:23331413 | 1 | Review-level, locus-specific evidence: the (TGGAA)n-containing insertion lies in the BEAN/TK2 shared intronic region and insertion length inversely correlates with age at onset, supporting length-dependent toxicity. |
| Functional Alteration | Patient cells | PMID:36563608 | 1 | Review-level evidence: the source summarizes neurotoxic RNA foci in human SCA31 Purkinje cells; original patient-cell experimental data are not presented in this review. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.