NOP53
protein-codingNOP53 ribosome biogenesis factor, the group of Ribosomal biogenesis factors
Gene summary
Enables 5S rRNA binding activity; identical protein binding activity; and p53 binding activity. Involved in several processes, including negative regulation of DNA-templated transcription; regulation of intracellular signal transduction; and regulation of protein metabolic process. Located in cytosol; nuclear lumen; and rDNA heterochromatin. [provided by Alliance of Genome Resources, Jun 2026]
- GLTSCR2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NOP53 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015710.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 2 | 3 | 10 | ||
| missense | 126 | 4 | 130 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 134 | 6 | 3 | 143 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056525.2 | 13 | MANE Select | |
| Ensembl | ENSP00000246802.4 | 13 | MANE Select | |
| Ensembl | ENSP00000470773.1 | 5 | Standard | |
| Ensembl | ENSP00000468948.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Herpes simplex infection - Homo sapiens (human)
Biological Process
- ribosomal large subunit assembly
- negative regulation of transcription by RNA polymerase II
- regulation of protein phosphorylation
- DNA repair
- rRNA processing
Molecular Function
- p53 binding
- RNA binding
- protein binding
- 5S rRNA binding
- identical protein binding
Cellular Component
- fibrillar center
- nucleoplasm
- nucleolus
- cytosol
- rDNA heterochromatin
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000246802
- Coding exons
- 13
- Length
- 11537
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125744
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.647 | 306 | 276 | 1.11 | 0.0000182 | 2932 |
| Missense (PolyPhen) | 84 | 82.507 | 1.0181 | 857 | ||
| Synonymous | -1.99 | 152 | 124 | 1.23 | 0.00000827 | 997 |
| Loss of Function | 3.40 | 6 | 24.0 | 0.250 | 0.00000115 | 294 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000079 | 0.000079 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Nucleolar protein which is involved in the integration of the 5S RNP into the ribosomal large subunit during ribosome biogenesis (PubMed:24120868). In ribosome biogenesis, may also play a role in rRNA transcription (PubMed:27729611). Also functions as a nucleolar sensor that regulates the activation of p53/TP53 in response to ribosome biogenesis perturbation, DNA damage and other stress conditions (PubMed:21741933, PubMed:24120868, PubMed:27829214). DNA damage or perturbation of ribosome biogenesis disrupt the interaction between NOP53 and RPL11 allowing RPL11 transport to the nucleoplasm where it can inhibit MDM2 and allow p53/TP53 activation (PubMed:24120868, PubMed:27829214). It may also positively regulate the function of p53/TP53 in cell cycle arrest and apoptosis through direct interaction, preventing its MDM2-dependent ubiquitin-mediated proteasomal degradation (PubMed:22522597). Originally identified as a tumor suppressor, it may also play a role in cell proliferation and apoptosis by positively regulating the stability of PTEN, thereby antagonizing the PI3K-AKT/PKB signaling pathway (PubMed:15355975, PubMed:16971513, PubMed:27729611). May also inhibit cell proliferation and increase apoptosis through its interaction with NF2 (PubMed:21167305). May negatively regulate NPM1 by regulating its nucleoplasmic localization, oligomerization and ubiquitin-mediated proteasomal degradation (PubMed:25818168). Thereby, may prevent NPM1 interaction with MYC and negatively regulate transcription mediated by the MYC-NPM1 complex (PubMed:25956029). May also regulate cellular aerobic respiration (PubMed:24556985). In the cellular response to viral infection, may play a role in the attenuation of interferon-beta through the inhibition of DDX58/RIG-1 (PubMed:27824081). {ECO:0000269|PubMed:15355975, ECO:0000269|PubMed:16971513, ECO:0000269|PubMed:21167305, ECO:0000269|PubMed:21741933, ECO:0000269|PubMed:22522597, ECO:0000269|PubMed:24120868, ECO:0000269|PubMed:24556985, ECO:0000269|PubMed:25818168, ECO:0000269|PubMed:25956029, ECO:0000269|PubMed:27729611, ECO:0000269|PubMed:27824081, ECO:0000269|PubMed:27829214}.;
Recessive Scores
- pRec
- 0.181
Intolerance Scores
- RVIS EVS
- 0.4
- RVIS percentile EVS
- 76.41
Essentials
- Essential (gene trap)
- E