NOP56

Chr 20AD

NOP56 ribonucleoprotein

Also known as: NOL5A, SCA36

NCBI Gene: 10528ENSG00000101361UniProt: O00567

Nop56p is a yeast nucleolar protein that is part of a complex with the nucleolar proteins Nop58p and fibrillarin. Nop56p is required for assembly of the 60S ribosomal subunit and is involved in pre-rRNA processing. The protein encoded by this gene is similar in sequence to Nop56p and is also found in the nucleolus. Expansion of a GGCCTG repeat from 3-8 copies to 1500-2500 copies in an intron of this gene results in spinocerebellar ataxia 36. Multiple transcript variants encoding several different isoforms have been found for this gene, but the full-length nature of most of them has not been determined. [provided by RefSeq, Jul 2016]

Primary Disease Associations & Inheritance

Spinocerebellar ataxia 36MIM #614153
AD
160
ClinVar variants
26
Pathogenic / LP
0.62
pLI score
0
Active trials
Clinical Summary— NOP56
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 86 VUS of 160 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.40LOEUF
pLI 0.621
Z-score 3.99
OE 0.20 (0.11–0.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.60Z-score
OE missense 0.91 (0.82–1.00)
299 obs / 329.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.20 (0.11–0.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.82–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 6 / 29.3Missense obs/exp: 299 / 329.9Syn Z: -1.00

ClinVar Variant Classifications

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic2
VUS86
Likely Benign15
Benign12
Conflicting1
24
Pathogenic
2
Likely Pathogenic
86
VUS
15
Likely Benign
12
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
1
1
2
VUS
0
78
8
0
86
Likely Benign
0
3
5
7
15
Benign
0
4
2
6
12
Conflicting
—1
Total0854014140

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NOP56 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spinocerebellar ataxia 36

MIM #614153

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Long-read sequencing identified intronic (GGCCTG)n expansion in NOP56 in one SCA36 family and literature review.
Wang Q et al.·Clin Neurol Neurosurg
2022Review
Investigating Repeat Expansions in NIPA1, NOP56, and NOTCH2NLC Genes: A Closer Look at Amyotrophic Lateral Sclerosis Patients from Southern Italy.
Ruffo P et al.·Cells
2024Cohort
Association of Non-Coding Repeat Expansions with Parkinson's Disease Risk: Evidence from a UK Biobank-Based Whole-Genome Sequencing Study.
Hu Z et al.·Mov Disord
2026
Genetic and clinical analysis of spinocerebellar ataxia type 36 in Mainland China.
Zeng S et al.·Clin Genet
2016
Spinocerebellar ataxia 36 (SCA36): «Costa da Morte ataxia».
Arias M et al.·Neurologia
2017Review
[Spinocerebellar ataxia type 36 (nicknamed Asidan)].
Abe K et al.·Brain Nerve
2012Review
Exploration of PVT1 as a biomarker in prostate cancer.
Liang X et al.·Medicine (Baltimore)
2024
LncRNA PVT1 drives macrophage polarization and triple-negative breast cancer progression via PPARγ-mediated transcriptional activation​.
Zhang X et al.·Apoptosis
2026
Whole Exome Sequencing Indicating GGCCTG Hexanucleotide Repeat in Patients with Spinocerebellar Ataxia Type 36.
Chen R et al.·Neurodegener Dis
2024Cohort
Revealing the Key MSCs Niches and Pathogenic Genes in Influencing CEP Homeostasis: A Conjoint Analysis of Single-Cell and WGCNA.
Li W et al.·Front Immunol
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools