SCA36_NOP56
- Gene
- NOP56
- Disease
- SCA36
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 13
- Publications Reviewed
- 4
- Publication Span
- 13.75 years
- Last Updated
- 08/11/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
Autosomal dominant spinocerebellar ataxia 36 (SCA36) is caused by a heterozygous intronic GGCCTG hexanucleotide repeat expansion in NOP56. The relationship is supported by multiple SCA36 cohorts and families with repeat-positive affected individuals, autosomal dominant segregation/linkage evidence, and cohort screening showing NOP56 expansions among undiagnosed hereditary ataxia cases. Experimental support is mainly gene-level: NOP56 functions in box C/D snoRNP biogenesis and ribosomal RNA methylation, while several cited functional evidence rows require curator review because the provided sources do not directly test the SCA36 repeat locus.
Genetic evidence
Total: 12
| Singular Evidence | Probands | PMID:37332636 | 6 | NOP56 GGCCTG repeat expansion identified in 37 individuals from 16 apparently unrelated families with SCA36 in an Eastern Spain ataxia cohort; most families showed autosomal dominant transmission. |
| Collective Evidence | Computational | PMID:28761930 | 0.5 | Exome sequencing and SNP-array linkage analysis in two dominant ataxia families found chromosome 20 candidate regions including NOP56, with no rare coding ataxia-gene variants identified; RP-PCR/Southern blot then confirmed the intronic GGCCTG expansion. |
| Collective Evidence | Segregation | PMID:28761930 | 1.5 | Affected individuals in two families shared linked chromosome 20 haplotypes consistent with autosomal dominant inheritance; the study notes maximum LOD was limited by pedigree power and used linkage to prioritize NOP56 expansion testing. |
| Statistics | Case-control data | PMID:37332636 | 6 | Cohort screening identified NOP56 expansions in 16/297 hereditary ataxia pedigrees (5.4%) and 16/84 screened undiagnosed cerebellar ataxia families; no matched unaffected control group was reported in this study. |
Experimental evidence
Total: 1
| Function | Biochemical function | PMID:37810464 | 0.5 | Gene-level, not SCA36 locus-specific: NOP56 is described as a core scaffolding component of box C/D snoRNP complexes involved in ribosomal RNA methylation; no biochemical assay of the SCA36 expansion was performed. |
| Function | Regulatory impact | PMID:19620283 | 0.5 | Gene-level, not SCA36 locus-specific: siRNA depletion of NOP56 in HeLa cells altered U3/U8 snoRNA maturation levels, supporting a role in box C/D snoRNP biogenesis rather than an epigenetic effect of the SCA36 repeat. |
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.