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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NOP56
NOP56 ribonucleoprotein
Chromosome 20 · 20p13
NCBI Gene: 10528Ensembl: ENSG00000101361.18HGNC: HGNC:15911UniProt: O00567
260PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingprotein bindingsnoRNA bindingcadherin bindingspinocerebellar ataxia type 36neurodegenerative diseaseovarian neoplasmgenetic disorder
✦AI Summary

NOP56 encodes a highly conserved nucleolar protein that serves as a core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes, functioning primarily in ribosomal RNA processing and modification 1. The protein is essential for early to middle stages of 60S ribosomal subunit biogenesis and is required for the biogenesis of box C/D snoRNAs including U3, U8, and U14 1. NOP56 participates in the small subunit processome assembly in the nucleolus, where it works with other factors to facilitate RNA folding, modifications, and cleavage of pre-ribosomal RNA 1. The protein enhances rRNA 2'-O methylation through direct interaction with fibrillarin (FBL), strengthening the FBL-NOP56 interaction and facilitating box C/D snoRNP complex assembly 1. Disease relevance centers on spinocerebellar ataxia type 36 (SCA36), caused by intronic GGCCTG hexanucleotide repeat expansions in NOP56 that undergo repeat-associated non-AUG (RAN) translation, producing toxic poly(Gly-Pro) and poly(Pro-Arg) peptides 23. Loss-of-function studies in zebrafish demonstrate severe neurodegenerative phenotypes including cerebellar absence and CNS apoptosis 4. NOP56 also shows dysregulated expression in various cancers, suggesting potential tumor biomarker applications 56.

Sources cited
1
NOP56 is a core component of box C/D snoRNP complexes that enhances rRNA 2'-O methylation through interaction with fibrillarin
PMID: 33795875
2
NOP56 GGCCTG repeat expansions undergo RAN translation producing toxic peptides in SCA36
PMID: 40015643
3
Intronic GGCCTG expansions in NOP56 cause spinocerebellar ataxia type 36
PMID: 36368168
4
NOP56 loss-of-function in zebrafish causes severe neurodegenerative phenotype with cerebellar absence
PMID: 36009362
5
NOP56 is abnormally expressed in malignant tumors and has potential as tumor marker
PMID: 36741964
6
NOP56 is highly expressed in colorectal cancer samples
PMID: 39969382
Disease Associationsⓘ21
spinocerebellar ataxia type 36Open Targets
0.61Moderate
neurodegenerative diseaseOpen Targets
0.50Moderate
ovarian neoplasmOpen Targets
0.30Weak
genetic disorderOpen Targets
0.19Weak
cerebellar ataxiaOpen Targets
0.12Weak
Mild global developmental delayOpen Targets
0.12Weak
anemiaOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.03Suggestive
placenta praeviaOpen Targets
0.03Suggestive
hepatocellular carcinomaOpen Targets
0.02Suggestive
neuropathyOpen Targets
0.02Suggestive
optic neuritisOpen Targets
0.02Suggestive
Alzheimer diseaseOpen Targets
0.02Suggestive
bone remodeling diseaseOpen Targets
0.02Suggestive
autosomal dominant cerebellar ataxiaOpen Targets
0.02Suggestive
amyotrophic lateral sclerosisOpen Targets
0.02Suggestive
acute myeloid leukemiaOpen Targets
0.01Suggestive
Burkitts lymphomaOpen Targets
0.01Suggestive
lung cancerOpen Targets
0.01Suggestive
thyroid cancerOpen Targets
0.01Suggestive
Spinocerebellar ataxia 36UniProt
Pathogenic Variants3
NM_006392.4(NOP56):c.909G>A (p.Ala303=)Likely pathogenic
Spinocerebellar ataxia type 36
☆☆☆☆2021→ Residue 303
NM_006392.4(NOP56):c.3+71GGCCTG[(650_?)]Pathogenic
Spinocerebellar ataxia type 36
☆☆☆☆2014
NM_006392.4(NOP56):c.3+71_3GGCCTG[16_?]Pathogenic
Spinocerebellar ataxia type 36
☆☆☆☆2012
View on ClinVar ↗
Related Genes
DKC1Protein interaction100%MCCProtein interaction100%NCLProtein interaction100%NOP2Protein interaction100%UBTFProtein interaction100%RRP1Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
82%
Liver
58%
Brain
57%
Lung
57%
Heart
43%
Gene Interaction Network
Click a node to explore
NOP56DKC1MCCNCLNOP2UBTFRRP1
PROTEIN STRUCTURE
Preparing viewer…
PDB7MQA · 2.70 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.72LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.54 [0.41–0.72]
RankingsWhere NOP56 stands among ~20K protein-coding genes
  • #1,461of 20,598
    Most Researched260 · top 10%
  • #3,920of 5,498
    Most Pathogenic Variants3
  • #5,587of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedNOP56
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
The roles of NOP56 in cancer and SCA36.
PMID: 36741964
Pathol Oncol Res · 2023
1.00
2
A PRC2-independent function for EZH2 in regulating rRNA 2'-O methylation and IRES-dependent translation.
PMID: 33795875
Nat Cell Biol · 2021
0.90
3
Dissecting the mechanism of NOP56 GGCCUG repeat-associated non-AUG translation using cell-free translation systems.
PMID: 40015643
J Biol Chem · 2025
0.80
4
Association between promoter methylation and gene expression of
PMID: 34820124
Biomed Rep · 2022
0.70
5
Burkitt's lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis.
PMID: 24013231
Oncogene · 2014
0.68