| Domain | Key findings | Quantitative / implementation details | Suggested ontology terms | Evidence |
|---|---|---|---|---|
| Identity / identifiers | Spinocerebellar ataxia type 31 (SCA31), a disease-level aggregated Mendelian disorder; one of the most common autosomal-dominant cerebellar ataxias in Japan; also described as a pure cerebellar ataxia | MONDO:0007296; common synonyms: SCA31, spinocerebellar ataxia 31; other identifiers not firmly established from available context | MONDO:0007296 | (pqac-00000000, pqac-00000001, pqac-00000003) |
| Inheritance | Autosomal dominant; strong founder effect in Japan; age-dependent expression is likely, but formal penetrance estimates are not established in the available context | Founder disease; essentially absent in most non-Japanese populations except reported Japanese diaspora cases; anticipation not established from available context | HP:0000006 (Autosomal dominant inheritance) | (pqac-00000002, pqac-00000003, pqac-00000005) |
| Causal lesion | Pathogenic lesion is a 2.5-3.8 kb complex pentanucleotide repeat insertion in the shared intronic region of BEAN1 and TK2 at 16q22.1; (TGGAA)n is the disease-segregating pathogenic motif | Repeat composition includes (TGGAA)n, (TAGAA)n, (TAAAA)n, and (TAAAATAGAA)n; controls may carry nonpathogenic short (TAAAA)8-20 tracts; healthy controls rarely have insertions lacking TGGAA (~0.23%) | Gene: BEAN1, TK2; SO conceptually: intronic repeat expansion / short tandem repeat expansion | (pqac-00000001, pqac-00000002, pqac-00000004) |
| Phenotype / onset | Late-onset, slowly progressive cerebellar ataxia with truncal and limb ataxia, dysarthria/cerebellar speech, reduced muscle tone; usually without brainstem involvement; occasional reported parkinsonism or blepharospasm | Mean onset about 58.5-63.8 years; considered among the latest-onset SCAs | HP:0001251 (Ataxia); HP:0002060 (Dysarthria); HP:0001252 (Hypotonia); HP:0002313 (Cerebellar atrophy) | (pqac-00000002, pqac-00000003, pqac-00000005) |
| Progression / prognosis | Chronic lifelong course with slow progression; quantitative natural history available; disability accumulates gradually | SARA progression ~0.8 points/year; wheelchair dependence around 79.4 ± 1.7 years; death around 88.5 ± 0.7 years in reported cohort summaries | HP:0001251; NCIT:C99568 (Wheelchair dependence, approximate mapping not guaranteed) | (pqac-00000002, pqac-00000005) |
| Anatomy / pathology | Primary pathology is cerebellar, especially Purkinje-cell-predominant degeneration and cerebellar cortical atrophy; upper vermis atrophy is typical on MRI | Purkinje-cell nuclear RNA foci seen in ~30% of patient Purkinje cells; foci ~0.2-1.8 µm; pathology includes Purkinje cell loss, shrinkage, halo-like amorphous material, calbindin-positive somatic sprouts, synaptophysin-positive terminals, ubiquitin-positive degradation granules, Golgi fragmentation | UBERON:0002037 (cerebellum); UBERON:0002245 (cerebellar vermis); CL:0000121 (Purkinje cell); GO:0005730 (nucleolus not established), GO:0005634 (nucleus) | (pqac-00000002, pqac-00000004, pqac-00000005) |
| Mechanism | Repeat is bidirectionally transcribed; brain-specific BEAN1-derived (UGGAA)n RNA forms toxic secondary structures and RNA foci in Purkinje-cell nuclei; UGGAA RNA binds TDP-43, FUS, hnRNPA2/B1; toxicity is likely mediated by RNA toxicity plus repeat-associated translation to pentapeptide repeat protein | TDP-43 acts as an RNA chaperone in fly/in vitro systems and suppresses toxicity; UGGAA translation yields poly-WNGME pentapeptide repeat protein detected in patient Purkinje cells; some mechanistic steps remain inferred rather than fully proven in humans | GO:0008380 (RNA splicing, broad RBP relevance); GO:0003723 (RNA binding); GO:0016070 (RNA metabolic process); GO:0034644 (cellular response to UV? not applicable); GO:0031047 (gene silencing by RNA not established) | (pqac-00000001, pqac-00000002, pqac-00000004, pqac-00000007) |
| Diagnostics | Real-world diagnosis relies on targeted repeat-expansion testing in suspected hereditary ataxia; Southern blot and PCR-based methods are described; long-read sequencing and WGS-based repeat detection are emerging adjuncts for complex repeat loci | Historical SCA31 mapping used Southern blot, BAC tiling/shotgun sequencing, PCR/Sanger; 2014 hybrid short+long read sequencing resolved 2.3-3.1 kb SCA31 repeats in 11 samples; current general ataxia RE practice uses repeat-primed PCR or Southern blot, with WGS pipelines increasingly feasible | NCIT:C120299 (Genetic Testing); NCIT:C71484 (Magnetic Resonance Imaging); HP:0001272 (Cerebellar atrophy on neuroimaging, approximate phenotype mapping) | (pqac-00000008, pqac-00000009) |
| Treatment / trials | No disease-modifying therapy is established in available SCA31-specific context; management is supportive and rehabilitative; experimental preclinical strategies target toxic RNA structure/RBP balance | Preclinical naphthyridine carbamate dimer (NCD) binds UGGAA repeats and reduced foci/degeneration in fly systems; trial search found no clearly relevant SCA31-specific interventional trial | NCIT:C15413 (Physical Therapy); NCIT:C15697 (Occupational Therapy); NCIT:C94533 (Speech Therapy); experimental small-molecule therapy not established | (pqac-00000007) |
| Epidemiology | Strongly enriched in Japan; reported as the third most frequent SCA in Japan; rare in neighboring Asian populations and absent from large European cohorts; Brazilian cases linked to Japanese ancestry support founder effect | One review notes 99.7% of controls carry short 8-20 TAAAA repeats at the locus; disease largely population-restricted | MONDO:0007296; HP:0012823 (Founder effect, no HPO term standardly used for disease, use narrative) | (pqac-00000001, pqac-00000003, pqac-00000005) |
| Environmental / protective factors | No established environmental, infectious, lifestyle, or protective factors were identified in the available SCA31-specific evidence; gene-environment interaction not established | Not established / unknown | None reliably assignable | (pqac-00000002, pqac-00000003) |
| Models | Drosophila transgenic models expressing expanded UGGAA/TGGAA repeats recapitulate RNA foci, degeneration, locomotor defects, and shortened lifespan; used for modifier and small-molecule testing | Toxicity is length- and expression-level-dependent; TDP-43/FUS/hnRNPA2B1 co-expression ameliorates phenotypes; poly-WNGME burden correlates with severity in flies | NCBITaxon:7227 (Drosophila melanogaster); CL terms not directly applicable to fly eye models; GO:0003723 (RNA binding) | (pqac-00000002, pqac-00000004, pqac-00000007) |


*Table: This table condenses the highest-confidence, knowledge-base-ready facts on Spinocerebellar Ataxia Type 31, including its causal repeat expansion, core phenotype, mechanistic evidence, diagnostics, and model systems. It also flags domains where the current evidence is limited or not established.*