Curation SCA31 BEAN1

Gene BEAN1

Disease SCA31

Inheritance AD

Score

9 + 3 = 12 / 18

Genetic + experimental = total

Classification

Definitive

Refuted

Moderate

Definitive

Last Updated 08/11/2025

Pubs Reviewed 4

Publication Span 13.33 years

Publication Interval 13.33 years

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.

All criTRia Curations Locus Page

Genetic evidence

Total: 9

Per page

Category	Type	Citation	Score	Details
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

Per page

Category	Type	Citation	Score	Details
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.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.