NOP53

Summary

NOP53 (NOP53 ribosome biogenesis factor, HGNC:4333) is a protein-coding gene on chromosome 19q13.33, encoding Ribosome biogenesis protein NOP53 (Q9NZM5). Nucleolar protein which is involved in the integration of the 5S RNP into the ribosomal large subunit during ribosome biogenesis. It is a selective cancer dependency (DepMap: 76.4% of cell lines).

Enables 5S rRNA binding activity; identical protein binding activity; and p53 binding activity. Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; regulation of intracellular signal transduction; and regulation of primary metabolic process. Located in cytosol; nuclear lumen; and rDNA heterochromatin.

Source: NCBI Gene 29997 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 140 total
• Cancer dependency (DepMap): dependent in 76.4% of screened cell lines
• MANE Select transcript: NM_015710

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4333
Approved symbol	NOP53
Name	NOP53 ribosome biogenesis factor
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	PICT-1, PICT1
Ensembl gene	ENSG00000105373
Ensembl biotype	protein_coding
OMIM	605691
Entrez	29997

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000246802, ENST00000594182, ENST00000594525, ENST00000595143, ENST00000597985, ENST00000598285, ENST00000598681, ENST00000598959, ENST00000599253, ENST00000599582, ENST00000600266, ENST00000600410, ENST00000856732, ENST00000856733, ENST00000856734, ENST00000917283, ENST00000917284, ENST00000953484

RefSeq mRNA: 1 — MANE Select: NM_015710 NM_015710

CCDS: CCDS12705

Canonical transcript exons

ENST00000246802 — 13 exons

Exon	Start	End
ENSE00001267516	47755756	47755822
ENSE00003130331	47745546	47745783
ENSE00003161900	47756999	47757058
ENSE00003460562	47750178	47750286
ENSE00003470105	47754709	47754891
ENSE00003484575	47751520	47751590
ENSE00003486603	47754527	47754631
ENSE00003516979	47755348	47755523
ENSE00003572408	47756528	47756604
ENSE00003640101	47750908	47751107
ENSE00003644232	47756688	47756744
ENSE00003655200	47752512	47752607
ENSE00003677143	47746967	47747031

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.3863 / max 287.9520, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176715	35.3143	1821
176717	0.5157	242
176716	0.4604	214
176718	0.0958	46

Top tissues by expression

266 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	99.62	gold quality
body of pancreas	UBERON:0001150	99.58	gold quality
right ovary	UBERON:0002118	99.58	gold quality
skin of leg	UBERON:0001511	99.55	gold quality
upper arm skin	UBERON:0004263	99.55	gold quality
embryo	UBERON:0000922	99.54	gold quality
skin of abdomen	UBERON:0001416	99.54	gold quality
ganglionic eminence	UBERON:0004023	99.54	gold quality
endocervix	UBERON:0000458	99.52	gold quality
body of uterus	UBERON:0009853	99.45	gold quality
right uterine tube	UBERON:0001302	99.43	gold quality
ectocervix	UBERON:0012249	99.42	gold quality
granulocyte	CL:0000094	99.41	gold quality
cortical plate	UBERON:0005343	99.41	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.41	gold quality
ventricular zone	UBERON:0003053	99.39	gold quality
mucosa of stomach	UBERON:0001199	99.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.38	gold quality
body of stomach	UBERON:0001161	99.37	gold quality
right lobe of thyroid gland	UBERON:0001119	99.33	gold quality
lower esophagus mucosa	UBERON:0035834	99.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.33	gold quality
lower esophagus	UBERON:0013473	99.32	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.32	gold quality
left uterine tube	UBERON:0001303	99.29	gold quality
left lobe of thyroid gland	UBERON:0001120	99.28	gold quality
minor salivary gland	UBERON:0001830	99.27	gold quality
uterine cervix	UBERON:0000002	99.23	gold quality
colonic epithelium	UBERON:0000397	99.23	gold quality
saliva-secreting gland	UBERON:0001044	99.20	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-HCAD-8	yes	1557.42
E-HCAD-1	yes	111.37
E-MTAB-8142	yes	105.09
E-MTAB-6701	yes	94.67
E-CURD-122	yes	92.89
E-MTAB-9467	yes	65.75
E-CURD-88	yes	48.50
E-MTAB-8410	yes	36.88
E-HCAD-9	yes	24.36
E-CURD-46	yes	20.38
E-GEOD-125970	yes	17.51
E-CURD-112	yes	5.55
E-GEOD-139324	no	1580.46
E-MTAB-8207	no	1459.15
E-HCAD-32	no	1108.41

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 76.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 36)

• These results suggest that PICT-1 plays a role in phosphatidylinositol 3,4,5-trisphosphate signals through controlling PTEN protein stability. (PMID:16971513)
• results suggest that the induction of PTEN-modulated apoptosis is one of the putative mechanisms of tumor suppressive activity by GLTSCR2 (PMID:17657248)
• GLTSCR2 as a proapoptotic protein sensitizing cells to hypoxic injury when overexpressed (PMID:17890897)
• GLTSCR2 expression is down-regulated in glioblastomas. Direct sequencing analysis and fluorescence in situ hybridization clearly demonstrates the presence of genetic alterations, such as a nonsense mutation and deletion, in the GLTSCR2 gene. (PMID:18729076)
• study describes a novel interaction between KS-Bcl-2 & PICT-1 cellular protein, encoded by a candidate tumor suppressor gene, GLTSCR2; show this interaction specifically targets KS-Bcl-2 to the nucleolus & decreases its antiapoptotic activity (PMID:20042497)
• Our results show a down-regulation of GLTSCR2 in seborrheic keratosis, indicating that GLTSCR2 may have a protective effect on the development of SK. (PMID:20185249)
• merlin mediates PICT-1-induced growth inhibition by translocating to the nucleolus and binding PICT-1 (PMID:21167305)
• GLTSCR2 seems to act as a tumor suppressor by participating in optimal DNA damage response because DNA damage is a frequent and crucial event in oncogenesis. (PMID:21741933)
• PICT1 is a potent regulator of the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolus. (PMID:21804542)
• PICT-1 exhibits a nucleolar distribution similar to proteins involved in ribosomal RNA processing, yet does not colocalize precisely with either UBF1 or Fibrillarin under normal or stressed conditions. (PMID:22292050)
• The glioma tumor-suppressor candidate region gene 2 (GLTSCR2)is as a new member of the nucleolus-nucleoplasmic axis for p53 regulation. (PMID:22522597)
• Repeated hypoxia downregulates p53-upstream regulator, GLTSCR2, which resulted in increased death resistance and invasive potential of glioblastoma cells. Restoration of GLTSCR2 expression suppressed the malignant potential of hypoxia-selected cells. (PMID:22850112)
• High PICT1 expression is associated with hepatocellular carcinoma. (PMID:23532381)
• GLTSCR2 functions as a tumor suppressor in prostatic adenocarcinomas. (PMID:23920125)
• GLTSCR2 is down-regulated in squamous cell carcinomas of the skin and UV light exposure decreases the stability of GLTSCR2 and sensitizes keratinocytes to DNA damage. (PMID:23942755)
• Findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. (PMID:24045667)
• GLTCR2 may play a role in the tumorigenesis, progression and biological behavior in breast cancer. (PMID:24054033)
• GLTSCR2 controls cellular proliferation and metabolism via the transcription factor Myc, and is induced by mitochondrial stress, suggesting it may constitute a significant component of the mitochondrial signaling pathway. (PMID:24556985)
• Authors confirmed the interaction of PICT-1 with itself by direct yeast two-hybrid assay and also showed self-association of PICT-1 in mammalian cells by co-immunoprecipitation and fluorescence resonance energy transfer assays. (PMID:24735870)
• These results suggest that PICT1 employs atypical proteasome-mediated degradation machinery to sense nucleolar stress within the nucleolus. (PMID:24923447)
• We demonstrated the GLTSCR2 expression decreased with the rise of the grade of cervical lesions; GLTSCR2 may play an important role in carcinogenesis of cervical cancer (PMID:25118835)
• Data show that tumor sppressor protein GLTSCR2 down-regulates total nucleophosmin (NPM) expression levels by decreasing its protein stability. (PMID:25818168)
• GLTSCR2 was an upstream negative regulator of the nucleophosmin (NPM)-MYC axis involved in controlling the transcriptional activity of MYC. GLTSCR2 may be a candidate for suppressing the growth of cancer cells stimulated by MYC hyperactivation. (PMID:25956029)
• The expression of GLTSCR2 was suppressed in renal cell carcinomas, accentuating the malignant phenotype. (PMID:26724143)
• GLTSCR2 is crucial for normal cellular function as well as for preventing the development or progression of cancer. The JNK-c-jun axis is indispensible for regulating the activities of GLTSCR2. (PMID:26903295)
• GLTSCR2 is a crucially involved in the positive regulation of telomerase and chromosome stability. (PMID:27357325)
• PICT-1 triggers pro-death autophagy through inhibition of rRNA transcription and the inactivation of AKT/mTOR/p70S6K pathway in glioblastoma cells. (PMID:27729611)
• The study presented evidence that viral infection induced translocation of GLTSCR2 from nucleus to cytoplasm, and cytoplasmic translocation enabled GLTSCR2 to effectively attenuate IFN-beta and support viral replication; however, viral infection did not result in elevating GLTSCR2 in cells. (PMID:27824081)
• PICT-1 is a major nucleolar sensor of the DNA damage repair response and an important upstream regulator of p53 via the RPL11-MDM2-p53 pathway. (PMID:27829214)
• Codon 389 polymorphism in PICT-1 is a risk factor for uterine cervical cancers.PICT-1 counteracts HPV-induced p53 degradation. (PMID:27996172)
• The findings of this study suggest that disruption of PICT-1 protein expression and codon 389 polymorphism can contribute to the pathogenesis or neoplastic progression of endometrial cancer. (PMID:29617699)
• Blocking cytoplasmic translocation of nucleolar protein NOP53 by deleting its nuclear export sequence abrogated its support of viral replication. Recombinant N3-T protein, containing NOP53 residues 330-432 and a human immunodeficiency virus-derived cell-penetrating Tat peptide, attenuated the expression of IFN-beta; and IFN-stimulated genes, as well as decreased the phosphorylation of interferon regulatory factor3. (PMID:29677136)
• Downregulation of NOP53 Ribosome Biogenesis Factor Leads to Abnormal Nuclear Division and Chromosomal Instability in Human Cervical Cancer Cells. (PMID:30421090)
• Germline variant p. Asp31His was present in all affected members in three families with familial non-medullary thyroid cancer. NOP53 is likely a low-penetrant gene implicated in FNMTC. (PMID:31703244)
• PICT1 is critical for regulating the Rps27a-Mdm2-p53 pathway by microtubule polymerization inhibitor against cervical cancer. (PMID:34166715)
• MTR4 adaptor PICT1 functions in two distinct steps during pre-rRNA processing. (PMID:36403484)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nop53	ENSDARG00000100452
mus_musculus	Nop53	ENSMUSG00000041560
rattus_norvegicus	Nop53	ENSRNOG00000013023
drosophila_melanogaster	CG1785	FBGN0030061
caenorhabditis_elegans		WBGENE00012692

Protein

Protein identifiers

Ribosome biogenesis protein NOP53 — Q9NZM5 (reviewed: Q9NZM5)

Alternative names: Glioma tumor suppressor candidate region gene 2 protein, Protein interacting with carboxyl terminus 1, p60

All UniProt accessions (5): Q9NZM5, M0QX73, M0QYZ9, M0QZ34, M0QZU5

UniProt curated annotations — full annotation on UniProt →

Function. Nucleolar protein which is involved in the integration of the 5S RNP into the ribosomal large subunit during ribosome biogenesis. In ribosome biogenesis, may also play a role in rRNA transcription. 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. 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. 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. 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. May also inhibit cell proliferation and increase apoptosis through its interaction with NF2. May negatively regulate NPM1 by regulating its nucleoplasmic localization, oligomerization and ubiquitin-mediated proteasomal degradation. Thereby, may prevent NPM1 interaction with MYC and negatively regulate transcription mediated by the MYC-NPM1 complex. May also regulate cellular aerobic respiration. In the cellular response to viral infection, may play a role in the attenuation of interferon-beta through the inhibition of RIGI.

Subunit / interactions. Homooligomer. Interacts with PTEN; regulates PTEN phosphorylation and increases its stability. Interacts with RPL11; retains RPL11 into the nucleolus. Interacts with CDKN2A/isoform tumor suppressor ARF; the interaction is direct and promotes ARF nucleoplasmic relocalization and ubiquitin-mediated proteasomal degradation. Interacts with NPM1; the interaction is direct and competitive with MYC. Interacts with NF2 (via FERM domain); the interaction is direct. Interacts with p53/TP53 (via the oligomerization region); the interaction is direct and may prevent the MDM2-mediated proteasomal degradation of p53/TP53. Interacts with RIGI; may regulate RIGI through USP15-mediated ‘Lys-63’-linked deubiquitination. Interacts with UBTF. (Microbial infection) Interacts with herpes simplex virus 1 early proteins ICP22 and ICP0. (Microbial infection) Interacts with Human herpesvirus 8 protein ORF16; may sequester ORF16 in host nucleolus and reduce its antiapoptotic activity.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm.

Tissue specificity. Expressed at high levels in heart and pancreas, moderate levels in placenta, liver, skeletal muscle, and kidney, and low levels in brain and lung.

Post-translational modifications. Ubiquitin-mediated proteasomal degradation is regulated by c-JUN. It is associated with relocalization to the nucleoplasm and decreased homooligomerization. Phosphorylated upon DNA damage probably by ATM and DNA-PK; may regulate NOP53 degradation.

Induction. Down-regulated by nucleolar stress through ubiquitin-independent proteasomal degradation (at protein level). Up-regulated upon mitochondrial stress (at protein level). Expression of the protein might be regulated by DNA damage but results are not consistent.

Similarity. Belongs to the NOP53 family.

RefSeq proteins (1): NP_056525* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011687	Nop53/GLTSCR2	Family

Pfam: PF07767

UniProt features (29 total): region of interest 7, sequence conflict 7, modified residue 4, mutagenesis site 4, compositionally biased region 3, sequence variant 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
8FLE	ELECTRON MICROSCOPY	2.48
8FL3	ELECTRON MICROSCOPY	2.53
8FL7	ELECTRON MICROSCOPY	2.55
8FLB	ELECTRON MICROSCOPY	2.55
8FLD	ELECTRON MICROSCOPY	2.58
8FL6	ELECTRON MICROSCOPY	2.62
8FLA	ELECTRON MICROSCOPY	2.63
8FL2	ELECTRON MICROSCOPY	2.67
8FL4	ELECTRON MICROSCOPY	2.89
8INF	ELECTRON MICROSCOPY	3
8FKZ	ELECTRON MICROSCOPY	3.04
8INE	ELECTRON MICROSCOPY	3.2
8IPY	ELECTRON MICROSCOPY	3.2
8IR3	ELECTRON MICROSCOPY	3.5
8IPX	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZM5-F1	79.84	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 2, 29, 93, 305

Mutagenesis-validated functional residues (4):

Position	Phenotype
233	decreased phosphorylation, degradation and increased interaction with rpl11 in response to dna damage; when associated w
233	loss of localization to the nucleolus and in response to dna damage increased degradation and decreased interaction with
289	decreased degradation in response to dna damage. decreased phosphorylation, degradation and increased interaction with r
289	loss of localization to the nucleolus and in response to dna damage increased degradation and decreased interaction with

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 310 (showing top): RNGTGGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_RIBOSOME_BIOGENESIS, WANG_CLIM2_TARGETS_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PHOSPHORYLATION, MODULE_255, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_317, GOBP_RIBOSOME_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (24): ribosomal large subunit assembly (GO:0000027), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of protein phosphorylation (GO:0001932), DNA repair (GO:0006281), rRNA processing (GO:0006364), DNA damage response (GO:0006974), mitotic G2 DNA damage checkpoint signaling (GO:0007095), negative regulation of protein-containing complex assembly (GO:0031333), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), regulation of RIG-I signaling pathway (GO:0039535), regulation of apoptotic process (GO:0042981), protein stabilization (GO:0050821), regulation of cell cycle (GO:0051726), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), cellular response to hypoxia (GO:0071456), regulation of signal transduction by p53 class mediator (GO:1901796), negative regulation of signal transduction by p53 class mediator (GO:1901797), negative regulation of transcription of nucleolar large rRNA by RNA polymerase I (GO:1901837), protein localization to nucleolus (GO:1902570), positive regulation of protein K63-linked deubiquitination (GO:1903006), regulation of aerobic respiration (GO:1903715), protein localization to nucleoplasm (GO:1990173), ribosome biogenesis (GO:0042254)

GO Molecular Function (5): p53 binding (GO:0002039), RNA binding (GO:0003723), 5S rRNA binding (GO:0008097), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (6): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), nucleus (GO:0005634), rDNA heterochromatin (GO:0033553)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular response to stress	2
regulation of proteasomal ubiquitin-dependent protein catabolic process	2
proteasome-mediated ubiquitin-dependent protein catabolic process	2
negative regulation of intracellular signal transduction	2
signal transduction by p53 class mediator	2
protein binding	2
nuclear lumen	2
protein-RNA complex assembly	1
ribosome assembly	1
ribosomal large subunit biogenesis	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
protein phosphorylation	1
regulation of protein modification process	1
regulation of phosphorylation	1
DNA metabolic process	1
DNA damage response	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
regulation of protein-containing complex assembly	1
negative regulation of cellular component organization	1
protein-containing complex assembly	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
RIG-I signaling pathway	1
regulation of cytoplasmic pattern recognition receptor signaling pathway	1
apoptotic process	1
regulation of programmed cell death	1
regulation of protein stability	1
cell cycle	1
regulation of cellular process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1

Protein interactions and networks

STRING

2286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOP53	AGL	P35573	983
NOP53	MTREX	P42285	959
NOP53	PTEN	P60484	937
NOP53	BICRA	Q9NZM4	778
NOP53	NIP7	Q9Y221	771
NOP53	RPL11	P25121	763
NOP53	UTP18	Q9Y5J1	729
NOP53	GNL2	Q13823	723
NOP53	NSA2	O95478	719
NOP53	RPF2	Q9H7B2	716
NOP53	RSL24D1	Q9UHA3	665
NOP53	NVL	O15381	618
NOP53	WDR12	Q9GZL7	616
NOP53	PIH1D1	Q9NWS0	616
NOP53	WDR74	Q6RFH5	608

IntAct

184 interactions, top by confidence:

A	B	Type	Score
TSPYL2	NOP53	psi-mi:“MI:0915”(physical association)	0.740
HMGB2	MIEN1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RPL10A	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
SLX4	ERCC1	psi-mi:“MI:0914”(association)	0.640
CPSF3	CPSF4	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
HMGB2	NOP53	psi-mi:“MI:0915”(physical association)	0.620
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
NPM1	NVL	psi-mi:“MI:0914”(association)	0.610
CSNK2A1	SURF6	psi-mi:“MI:0914”(association)	0.590
	NOP53	psi-mi:“MI:0915”(physical association)	0.560
CEP70	NOP53	psi-mi:“MI:0915”(physical association)	0.560
NOP53	MDM2	psi-mi:“MI:0915”(physical association)	0.550
NOP53	CFTR	psi-mi:“MI:0915”(physical association)	0.550
NSA2	TYW5	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
PDGFB	DKC1	psi-mi:“MI:0914”(association)	0.530
ZCRB1	DKC1	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
CASQ2	PES1	psi-mi:“MI:0914”(association)	0.530

BioGRID (422): GLTSCR2 (Two-hybrid), GLTSCR2 (Two-hybrid), GLTSCR2 (Affinity Capture-Western), GLTSCR2 (Affinity Capture-Western), GLTSCR2 (Co-localization), GLTSCR2 (Affinity Capture-MS), GLTSCR2 (Affinity Capture-MS), GLTSCR2 (Affinity Capture-MS), GLTSCR2 (Affinity Capture-MS), GLTSCR2 (Affinity Capture-MS), GLTSCR2 (Co-fractionation), GLTSCR2 (Co-fractionation), GLTSCR2 (Co-fractionation), GLTSCR2 (Co-fractionation), MPHOSPH10 (Co-fractionation)

ESM2 similar proteins: A1A5P2, A6QNR1, A8WY26, D3ZND0, O15213, O59678, P27672, P78316, Q0V8M0, Q15050, Q24K12, Q28IV8, Q2KIH4, Q2KII6, Q3T0Q8, Q3T0Z5, Q3UFY0, Q4KLC4, Q5M985, Q5RAS1, Q5RJT2, Q5TAP6, Q5TJE7, Q5ZKM1, Q640M1, Q6EJB6, Q6P0I6, Q6PFJ1, Q8BK35, Q8IY81, Q8N9T8, Q8NEJ9, Q8R3N1, Q8VDQ9, Q96BZ8, Q96EU6, Q9BRP8, Q9BRR8, Q9BVJ6, Q9C086

Diamond homologs: Q12080, Q8BK35, Q9NZM5, Q9UUI4, O22892, Q9W3C2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATM	“down-regulates quantity by destabilization”	NOP53	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 194 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
rRNA modification in the nucleus and cytosol	9	12.9×	1e-06
Peptide chain elongation	12	11.6×	5e-08
Viral mRNA Translation	12	11.6×	5e-08
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	12	11.5×	5e-08
Formation of a pool of free 40S subunits	13	11.1×	4e-08
Selenocysteine synthesis	12	11.0×	5e-08
Eukaryotic Translation Termination	12	11.0×	5e-08
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	12	10.8×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
liver regeneration	7	20.4×	9e-06
ribosomal small subunit biogenesis	12	15.6×	7e-09
cytoplasmic translation	13	13.8×	7e-09
ribosomal large subunit biogenesis	5	12.7×	5e-03
negative regulation of viral genome replication	5	10.7×	1e-02
rRNA processing	13	10.5×	9e-08
translation	15	8.8×	6e-08
mRNA processing	11	5.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

140 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	106
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1639 predictions. Top by Δscore:

Variant	Effect	Δscore
19:47745779:AGCGG:A	donor_gain	1.0000
19:47745780:GCGG:G	donor_gain	1.0000
19:47745780:GCGGG:G	donor_gain	1.0000
19:47745781:CGGGT:C	donor_loss	1.0000
19:47745782:GG:G	donor_gain	1.0000
19:47745783:GG:G	donor_gain	1.0000
19:47745783:GGT:G	donor_loss	1.0000
19:47745784:G:GG	donor_gain	1.0000
19:47745784:GTA:G	donor_loss	1.0000
19:47745785:T:G	donor_loss	1.0000
19:47746965:A:AG	acceptor_gain	1.0000
19:47746965:AGT:A	acceptor_gain	1.0000
19:47746966:G:GA	acceptor_gain	1.0000
19:47746966:GT:G	acceptor_gain	1.0000
19:47746966:GTG:G	acceptor_gain	1.0000
19:47750170:A:AG	acceptor_gain	1.0000
19:47750171:T:G	acceptor_gain	1.0000
19:47750174:TTAG:T	acceptor_gain	1.0000
19:47750174:TTAGG:T	acceptor_loss	1.0000
19:47750175:TA:T	acceptor_loss	1.0000
19:47750175:TAGG:T	acceptor_gain	1.0000
19:47750176:A:AG	acceptor_gain	1.0000
19:47750176:AG:A	acceptor_gain	1.0000
19:47750176:AGG:A	acceptor_gain	1.0000
19:47750176:AGGGC:A	acceptor_gain	1.0000
19:47750177:G:GA	acceptor_gain	1.0000
19:47750177:GG:G	acceptor_gain	1.0000
19:47750177:GGG:G	acceptor_gain	1.0000
19:47750177:GGGC:G	acceptor_gain	1.0000
19:47750177:GGGCT:G	acceptor_gain	1.0000

AlphaMissense

3030 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:47745701:T:A	W48R	0.995
19:47745701:T:C	W48R	0.995
19:47745703:G:C	W48C	0.995
19:47745703:G:T	W48C	0.995
19:47756561:A:C	S444R	0.988
19:47756563:C:A	S444R	0.988
19:47756563:C:G	S444R	0.988
19:47756731:T:C	F473L	0.988
19:47756733:C:A	F473L	0.988
19:47756733:C:G	F473L	0.988
19:47745746:T:C	F63L	0.985
19:47745748:C:A	F63L	0.985
19:47745748:C:G	F63L	0.985
19:47745774:G:C	R72P	0.985
19:47752602:C:G	H254D	0.985
19:47756583:T:A	I451N	0.983
19:47747001:T:C	F87L	0.981
19:47747003:C:A	F87L	0.981
19:47747003:C:G	F87L	0.981
19:47751095:T:A	W196R	0.981
19:47751095:T:C	W196R	0.981
19:47756574:G:C	R448T	0.980
19:47756574:G:T	R448M	0.980
19:47745694:G:C	K45N	0.979
19:47745694:G:T	K45N	0.979
19:47756569:G:C	Q446H	0.979
19:47756569:G:T	Q446H	0.979
19:47756553:G:C	R441P	0.978
19:47755514:G:A	G407E	0.977
19:47756575:G:C	R448S	0.977

dbSNP variants (sampled 300 via entrez): RS1000011170 (19:47745891 T>C,G), RS1000072814 (19:47744508 C>A), RS1000235016 (19:47748932 C>A,G,T), RS1000519381 (19:47748041 A>C,G), RS1000585417 (19:47748755 C>G,T), RS1001097406 (19:47750043 G>T), RS1001350713 (19:47744776 C>G,T), RS1001426270 (19:47748298 A>G), RS1001434631 (19:47749006 A>G), RS1001501274 (19:47748793 C>T), RS1001776711 (19:47756876 C>T), RS1001801582 (19:47744471 C>G), RS1001833349 (19:47747786 T>C), RS1001874622 (19:47752021 C>T), RS1002051936 (19:47753187 T>C)

Disease associations

OMIM: gene MIM:605691 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
sodium arsenite	increases expression	2
Estradiol	affects expression, decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
bisphenol A	decreases expression	1
cobaltous chloride	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
chloropicrin	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Air Pollutants	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thimerosal	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.