Curation SCA36 NOP56

Gene NOP56
Disease SCA36
Inheritance AD
Score

12 + 1 = 13 / 18

Genetic + experimental = total
Classification
0
18
Refuted
Moderate
Definitive
Last Updated 08/11/2025
Pubs Reviewed 4
Publication Span 13.75 years
Publication Interval 13.75 years
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

Category
Type
Citation
Score
Details
Singular Evidence
Probands
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
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
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
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

Category
Type
Citation
Score
Details
Function
Biochemical function
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
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.

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