SCA7_ATXN7
- Gene
- ATXN7
- Disease
- SCA7
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 18
- Publications Reviewed
- 7
- Publication Span
- 22.92 years
- Last Updated
- 08/12/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
A heterozygous pathogenic CAG repeat expansion in the coding region of ATXN7 causes autosomal dominant spinocerebellar ataxia type 7 (SCA7), characterized by progressive cerebellar ataxia and retinal degeneration. Uploaded studies support the locus-disease relationship through segregation of expanded CAG alleles in SCA7 families, molecularly confirmed case/control cohorts across multiple populations, repeat-length associations with age at onset/anticipation, and experimental evidence that polyQ-expanded ataxin-7 disrupts STAGA/TFTC-mediated transcriptional regulation, forms nuclear inclusions, and causes disease-relevant phenotypes in cell and animal models.
Genetic evidence
Total: 12
| Singular Evidence | Probands | 6 | GeneReviews summarizes SCA7 as established by identification of a heterozygous abnormal ATXN7 CAG trinucleotide repeat expansion in a proband and notes that more than 1,000 affected individuals have been identified worldwide. | |
| Collective Evidence | Allele | 2 | GeneReviews defines ATXN7 CAG repeat ranges as normal 7–27, mutable normal 28–33, pathogenic reduced penetrance 34–36, and pathogenic full penetrance 37–460 repeats; longer repeats correlate with earlier onset, greater severity, and faster progression. | |
| Collective Evidence | Segregation | PMID:8908515 | 1.5 | In 8 SCA7 families, RED detected 150-240 bp CAG expansion products in all affected individuals; expansions cosegregated with disease (P < 0.000001, n = 66), with repeat-size instability observed in affected offspring. |
| Statistics | Case-control data | PMID:30721448 PMID:28597910 PMID:25900954 PMID:11030806 | 6 | Uploaded case-control/cohort studies support ATXN7 CAG expansion enrichment in SCA7: Chinese families showed affected alleles of 44-85 CAG versus 9-18 in 67 controls; Indian SCA7 families had 22 affected individuals with 40-94 CAG expansions and 382 population controls; rs6798742 haplotype association was replicated in Indian and Mexican expansion carriers. PMID 30721448 is a biomarker case-control study, not primary expansion-enrichment evidence. |
Experimental evidence
Total: 6
| Function | Biochemical function | PMID:18418675 | 0.5 | Gene-level/locus-relevant evidence: ataxin-7 is a core STAGA/TFTC transcription co-activator component with histone acetyltransferase-related function; polyQ expansion alters this activity. |
| Function | Protein interaction | PMID:18418675 | 0.5 | Gene-level/locus-relevant evidence: ataxin-7 is incorporated into STAGA/TFTC transcription co-activator complexes and mutant polyQ-expanded ataxin-7 perturbs interactions with transcriptional regulatory machinery. |
| Function | Regulatory impact | PMID:18418675 | 0.5 | PolyQ-expanded ataxin-7 alters SAGA/STAGA/TFTC histone acetyltransferase activity and chromatin/transcriptional regulation in disease-relevant experimental systems. |
| Functional Alteration | Patient cells | PMID:18418675 | 1 | Patient CNS tissue shows mutant ataxin-7 nuclear inclusions with ubiquitin-proteasome components and neurodegenerative pathology in SCA7-vulnerable regions; evidence is tissue/cell-level but not a separate locus-genotyping cohort. |
| Functional Alteration | Non-patient cells | PMID:18418675 | 0.5 | Non-patient cell models expressing mutant polyQ-expanded ataxin-7 show enhanced nuclear localization/toxicity and activation of apoptotic pathways, supporting a repeat-length-dependent toxic gain of function. |
| Models | Non-human model organism | PMID:18418675 | 2 | SCA7 mouse models expressing polyQ-expanded ataxin-7 develop gait ataxia, nuclear inclusions, Purkinje-cell dendritic degeneration, and non-cell-autonomous cerebellar pathology resembling human SCA7. |
| Models | Cell culture | PMID:18418675 | 1 | Cell-culture models expressing polyQ-expanded ataxin-7 reproduce disease-relevant molecular phenotypes, including altered transcriptional regulation, mutant protein accumulation, and cellular toxicity. |
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.