NOP2

Summary

NOP2 (NOP2 nucleolar protein, HGNC:7867) is a protein-coding gene on chromosome 12p13.31, encoding 28S rRNA (cytosine(4447)-C(5))-methyltransferase (P46087). S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C(5) position of cytosine 4447 in 28S rRNA. It is a common-essential gene (DepMap: required in 99.5% of cancer cell lines).

Enables rRNA (cytosine-C5-)-methyltransferase activity. Involved in positive regulation of cell population proliferation; regulation of signal transduction by p53 class mediator; and ribosome biogenesis. Located in nucleolus.

Source: NCBI Gene 4839 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 151 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_001258308

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7867
Approved symbol	NOP2
Name	NOP2 nucleolar protein
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	NOP120, NSUN1, p120
Ensembl gene	ENSG00000111641
Ensembl biotype	protein_coding
OMIM	164031
Entrez	4839

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 29 protein_coding, 7 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000322166, ENST00000382421, ENST00000399466, ENST00000400580, ENST00000536124, ENST00000536506, ENST00000537442, ENST00000537708, ENST00000538420, ENST00000538697, ENST00000540228, ENST00000541778, ENST00000542015, ENST00000542867, ENST00000542919, ENST00000542944, ENST00000544630, ENST00000545200, ENST00000545492, ENST00000545915, ENST00000546053, ENST00000872639, ENST00000872640, ENST00000872641, ENST00000872642, ENST00000935750, ENST00000935751, ENST00000935752, ENST00000935753, ENST00000935754, ENST00000935755, ENST00000935756, ENST00000935757, ENST00000935758, ENST00000962902, ENST00000962903, ENST00000962904, ENST00000962905

RefSeq mRNA: 5 — MANE Select: NM_001258308 NM_001033714, NM_001258308, NM_001258309, NM_001258310, NM_006170

CCDS: CCDS44811, CCDS58202, CCDS58203, CCDS58204

Canonical transcript exons

ENST00000322166 — 16 exons

Exon	Start	End
ENSE00000715273	6560698	6560787
ENSE00000715284	6566529	6566617
ENSE00001596900	6563614	6563771
ENSE00001691058	6563315	6563514
ENSE00003470387	6567816	6567922
ENSE00003486866	6560447	6560569
ENSE00003496556	6561884	6561971
ENSE00003498144	6563081	6563170
ENSE00003525513	6566777	6566822
ENSE00003537571	6560931	6561070
ENSE00003576317	6561664	6561804
ENSE00003585744	6566101	6566336
ENSE00003657776	6560098	6560326
ENSE00003787719	6563891	6563946
ENSE00003901436	6568207	6568291
ENSE00003903970	6556871	6557642

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.3234 / max 238.2841, expressed in 1810 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129119	25.3234	1810

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.21	gold quality
lower esophagus mucosa	UBERON:0035834	92.82	gold quality
lymph node	UBERON:0000029	92.80	gold quality
vermiform appendix	UBERON:0001154	92.17	gold quality
spleen	UBERON:0002106	90.84	gold quality
left uterine tube	UBERON:0001303	90.63	gold quality
gastrocnemius	UBERON:0001388	90.56	gold quality
islet of Langerhans	UBERON:0000006	90.26	gold quality
esophagus mucosa	UBERON:0002469	90.13	gold quality
muscle of leg	UBERON:0001383	89.89	gold quality
right lobe of thyroid gland	UBERON:0001119	89.61	gold quality
omental fat pad	UBERON:0010414	89.37	gold quality
adenohypophysis	UBERON:0002196	89.32	gold quality
tonsil	UBERON:0002372	89.28	gold quality
mucosa of transverse colon	UBERON:0004991	89.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.08	gold quality
left lobe of thyroid gland	UBERON:0001120	88.91	gold quality
pancreas	UBERON:0001264	88.91	gold quality
skin of abdomen	UBERON:0001416	88.89	gold quality
prostate gland	UBERON:0002367	88.87	gold quality
thyroid gland	UBERON:0002046	88.80	gold quality
sural nerve	UBERON:0015488	88.73	gold quality
pituitary gland	UBERON:0000007	88.70	gold quality
blood	UBERON:0000178	88.64	gold quality
body of stomach	UBERON:0001161	88.61	gold quality
bone marrow	UBERON:0002371	88.59	gold quality
esophagus	UBERON:0001043	88.49	gold quality
small intestine	UBERON:0002108	88.49	gold quality
metanephros cortex	UBERON:0010533	88.48	gold quality
skeletal muscle tissue	UBERON:0001134	88.41	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting NOP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-3606-3P	99.11	69.84	3254

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 9)

• Findings suggest a newly discovered role of Nop2 in both mature neurons and in cells possibly involved in the regeneration of nervous tissue (PMID:25481415)
• p120 has an rRNA:5-Methylcytosine-Methyltransferase activity. (PMID:26196125)
• NOL1 represents a new route by which telomerase activates transcription of cyclin D1 gene, thus maintaining cell proliferation capacity (PMID:26906424)
• Mechanistically, NOP2 associates with HIV-1 5’ LTR, interacts with HIV-1 TAR RNA by competing with HIV-1 Tat protein, as well as contributes to TAR m5C methylation. RNA MTase catalytic domain (MTD) of NOP2 mediates its competition with Tat and binding with TAR. Overall, these findings verified that NOP2 suppresses HIV-1 transcription and promotes viral latency. (PMID:32176734)
• Long noncoding RNA LINC00963 induces NOP2 expression by sponging tumor suppressor miR-542-3p to promote metastasis in prostate cancer. (PMID:32554858)
• Upregulated expression of NOP2 predicts worse prognosis of gastric adenocarcinoma by promoting tumor growth. (PMID:35381832)
• Human NOP2/NSUN1 regulates ribosome biogenesis through non-catalytic complex formation with box C/D snoRNPs. (PMID:36161484)
• NOP2-mediated m5C methylation of XPD is associated with hepatocellular carcinoma progression. (PMID:37498063)
• NOP2 facilitates EZH2-mediated epithelial-mesenchymal transition by enhancing EZH2 mRNA stability via m5C methylation in lung cancer progression. (PMID:39013911)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nop2	ENSDARG00000043304
mus_musculus	Nop2	ENSMUSG00000038279
rattus_norvegicus	Nop2	ENSRNOG00000018453
drosophila_melanogaster	CG8545	FBGN0033741
caenorhabditis_elegans		WBGENE00021073

Paralogs (2): NSUN5 (ENSG00000130305), NSUN6 (ENSG00000241058)

Protein

Protein identifiers

28S rRNA (cytosine(4447)-C(5))-methyltransferase — P46087 (reviewed: P46087)

Alternative names: Nucleolar protein 1, Nucleolar protein 2 homolog, Proliferating-cell nucleolar antigen p120, Proliferation-associated nucleolar protein p120

All UniProt accessions (7): P46087, F5GWB7, F5GYR3, F5H359, F5H5X6, F5H709, F5H8G6

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C(5) position of cytosine 4447 in 28S rRNA. Required for efficient rRNA processing and 60S ribosomal subunit biogenesis. Regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs and facilitates the recruitment of U3 and U8 snoRNAs to pre-90S ribosomal particles and their stable assembly into snoRNP complexes. May play a role in the regulation of the cell cycle and the increased nucleolar activity that is associated with the cell proliferation.

Subunit / interactions. Interacts with MCRS1. Interacts with WDR46. Interacts with RRP1B. Interacts with NPM1. Interacts with NOP56, FBL, RUVBL1 and NUFIP1.

Subcellular location. Nucleus. Nucleolus.

Post-translational modifications. Citrullinated by PADI4.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.

Isoforms (4)

UniProt ID	Names	Canonical?
P46087-1	1	yes
P46087-2	2
P46087-3	3
P46087-4	4

RefSeq proteins (5): NP_001028886, NP_001245237, NP_001245238, NP_001245239, NP_006161 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001678	MeTrfase_RsmB-F_NOP2_dom	Domain
IPR011023	Nop2p	Domain
IPR012586	NOP2_rpt	Repeat
IPR018314	RsmB/NOL1/NOP2-like_CS	Conserved_site
IPR023267	RCMT	Family
IPR023273	RCMT_NOP2	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR049560	MeTrfase_RsmB-F_NOP2_cat	Domain
IPR054728	RsmB-like_ferredoxin	Domain

Pfam: PF01189, PF08062, PF22458

Catalyzed reactions (Rhea), 1 shown:

• cytidine(4447) in 28S rRNA + S-adenosyl-L-methionine = 5-methylcytidine(4447) in 28S rRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:47792)

UniProt features (52 total): modified residue 18, compositionally biased region 9, region of interest 6, binding site 4, cross-link 3, splice variant 3, sequence conflict 3, short sequence motif 2, chain 1, active site 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8FKV	ELECTRON MICROSCOPY	2.47
8FKW	ELECTRON MICROSCOPY	2.5
8FKX	ELECTRON MICROSCOPY	2.59
8FKY	ELECTRON MICROSCOPY	2.67
8FKT	ELECTRON MICROSCOPY	2.81
8FKU	ELECTRON MICROSCOPY	2.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46087-F1	62.86	0.28

Functional residue map

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

Catalytic / active sites (1): 517 (nucleophile)

Ligand- & substrate-binding residues (4): 392–398; 416; 443; 460

Post-translational modifications (21): 36, 58, 67, 102, 164, 181, 185, 195, 649, 666, 675, 732, 734, 739, 776, 786, 801, 812, 71, 272 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
517	loss of catalytic activity. can rescue the rrna processing defects observed upon depletion of nop2.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-8869496	TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation

MSigDB gene sets: 221 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_RIBOSOME_BIOGENESIS, ENK_UV_RESPONSE_KERATINOCYTE_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_RIBOSOME_ASSEMBLY, GOBP_RNA_METHYLATION, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_RNA_MODIFICATION, GOBP_RIBOSOMAL_LARGE_SUBUNIT_ASSEMBLY, KORKOLA_EMBRYONAL_CARCINOMA_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GROSS_HYPOXIA_VIA_HIF1A_UP, GOBP_MATURATION_OF_LSU_RRNA, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION

GO Biological Process (11): ribosomal large subunit assembly (GO:0000027), maturation of LSU-rRNA (GO:0000470), rRNA processing (GO:0006364), positive regulation of cell population proliferation (GO:0008284), ribosomal large subunit biogenesis (GO:0042273), rRNA base methylation (GO:0070475), regulation of signal transduction by p53 class mediator (GO:1901796), RNA methylation (GO:0001510), RNA processing (GO:0006396), methylation (GO:0032259), ribosome biogenesis (GO:0042254)

GO Molecular Function (7): RNA binding (GO:0003723), rRNA (cytosine-C5-)-methyltransferase activity (GO:0009383), protein binding (GO:0005515), methyltransferase activity (GO:0008168), RNA methyltransferase activity (GO:0008173), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribosomal large subunit biogenesis	2
ribosome biogenesis	2
ribonucleoprotein complex biogenesis	2
methyltransferase activity	2
nuclear lumen	2
protein-RNA complex assembly	1
ribosome assembly	1
rRNA processing	1
RNA processing	1
rRNA metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
rRNA methylation	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
RNA modification	1
macromolecule methylation	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
metabolic process	1
nucleic acid binding	1
C-methyltransferase activity	1
rRNA (cytosine) methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity, acting on RNA	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOP2	RBM28	Q9NW13	849
NOP2	TRDMT1	O14717	827
NOP2	NIP7	Q9Y221	820
NOP2	FTSJ3	Q8IY81	813
NOP2	NSUN7	Q8NE18	806
NOP2	RSL24D1	Q9UHA3	776
NOP2	WDR74	Q6RFH5	768
NOP2	FBL	P22087	757
NOP2	EBNA1BP2	Q99848	744
NOP2	GNL2	Q13823	736
NOP2	GTPBP4	Q9BZE4	725
NOP2	RPF2	Q9H7B2	709
NOP2	NSUN2	Q08J23	704
NOP2	NSA2	O95478	691
NOP2	NOP58	Q9Y2X3	688

IntAct

220 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
SRP68	SRP72	psi-mi:“MI:0914”(association)	0.730
RRP1B	NPM1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NOP2	NIP7	psi-mi:“MI:0915”(physical association)	0.670
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
RBM34	RRP8	psi-mi:“MI:0914”(association)	0.640
KPNA6	NOP2	psi-mi:“MI:0915”(physical association)	0.560
NOP2	MT1F	psi-mi:“MI:0915”(physical association)	0.560
VPS52	NOP2	psi-mi:“MI:0915”(physical association)	0.560
CEP70	NOP2	psi-mi:“MI:0915”(physical association)	0.560
NOP2	CDCA7L	psi-mi:“MI:0915”(physical association)	0.560
MT1F	NOP2	psi-mi:“MI:0915”(physical association)	0.560
CDCA7L	NOP2	psi-mi:“MI:0915”(physical association)	0.560
NOP2	KPNA6	psi-mi:“MI:0915”(physical association)	0.560
RBM28	NOP2	psi-mi:“MI:0915”(physical association)	0.560
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
EED	EPOP	psi-mi:“MI:0914”(association)	0.530
NSA2	TYW5	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530

BioGRID (579): NOP2 (Two-hybrid), VPS52 (Two-hybrid), KPNA6 (Two-hybrid), CDCA7L (Two-hybrid), CEP70 (Two-hybrid), NOP2 (Affinity Capture-RNA), NOP2 (Affinity Capture-MS), NOP2 (Affinity Capture-MS), NOP2 (Affinity Capture-MS), NOP2 (Affinity Capture-MS), NOP2 (Biochemical Activity), NOP2 (Affinity Capture-MS), NOP2 (Affinity Capture-MS), NOP2 (Affinity Capture-MS), NOP2 (Affinity Capture-MS)

ESM2 similar proteins: A0LRM5, A0QNH4, A1KH33, A2C6Q5, B1VTI4, I6YHB0, L8FM21, O69690, P07935, P0A603, P17687, P46040, P46087, P46842, P55046, P55047, P55875, P58346, P64758, P64790, P65301, P65313, P65379, P65731, P71905, P9WGI0, P9WGI1, P9WI68, P9WI69, P9WJC0, P9WJC1, P9WJC4, P9WJC5, P9WJG4, P9WJG5, P9WJT0, P9WJT1, P9WK48, P9WK49, P9WK74

Diamond homologs: A0KKI5, A0KW34, A1AC00, A1RIZ0, A1S788, A1SWV0, A3D5D5, A3QDA2, A4SMI9, A4WBJ4, A4Y7J8, A6TB06, A6WP46, A7MKH5, A7N0K6, A7ZMV8, A8A133, A8AFL6, A8FWM8, A8GDM6, A8H3W2, A9L4E6, A9MNH4, A9MV57, B0TIZ6, B1J0Q3, B1KQN1, B1LD37, B1XHA3, B2U477, B2VJ83, B4SV89, B4TKI0, B4TY18, B5BHA6, B5F3P3, B5FE06, B5FTI4, B5R2S1, B5R8V2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 234 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
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	5	21.3×	9e-05
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	23	17.1×	5e-20
Peptide chain elongation	21	16.9×	2e-18
Viral mRNA Translation	21	16.9×	2e-18
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	21	16.7×	2e-18
Selenocysteine synthesis	21	16.0×	4e-18
Eukaryotic Translation Termination	21	16.0×	4e-18
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	21	15.7×	5e-18

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	5	27.7×	9e-05
chromosome condensation	6	24.9×	2e-05
ribosomal large subunit biogenesis	11	24.0×	2e-10
cytoplasmic translation	22	20.1×	7e-20
stem cell population maintenance	6	12.4×	8e-04
translation	24	12.2×	1e-16
ribosomal small subunit biogenesis	10	11.2×	4e-06
mRNA stabilization	6	10.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	117
Likely benign	10
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1881 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6560097:CCT:C	donor_gain	1.0000
12:6560323:CTAC:C	acceptor_gain	1.0000
12:6560325:ACCTG:A	acceptor_loss	1.0000
12:6560326:CCTG:C	acceptor_loss	1.0000
12:6560327:C:CA	acceptor_loss	1.0000
12:6560328:T:A	acceptor_loss	1.0000
12:6560331:A:AC	acceptor_gain	1.0000
12:6560331:A:C	acceptor_gain	1.0000
12:6560333:G:C	acceptor_gain	1.0000
12:6560333:G:GC	acceptor_gain	1.0000
12:6560419:C:A	donor_gain	1.0000
12:6560445:A:AC	donor_gain	1.0000
12:6560446:C:CT	donor_gain	1.0000
12:6560446:CT:C	donor_gain	1.0000
12:6560476:AGCCT:A	donor_gain	1.0000
12:6560480:T:TA	donor_gain	1.0000
12:6560694:TCAC:T	donor_loss	1.0000
12:6560696:A:AC	donor_gain	1.0000
12:6560696:AC:A	donor_gain	1.0000
12:6560696:ACCTT:A	donor_loss	1.0000
12:6560697:C:CC	donor_gain	1.0000
12:6560697:CC:C	donor_gain	1.0000
12:6560783:ACCAC:A	acceptor_gain	1.0000
12:6560784:CCAC:C	acceptor_gain	1.0000
12:6560784:CCACC:C	acceptor_gain	1.0000
12:6560785:CAC:C	acceptor_gain	1.0000
12:6560785:CACC:C	acceptor_gain	1.0000
12:6560786:AC:A	acceptor_gain	1.0000
12:6560787:CC:C	acceptor_gain	1.0000
12:6560787:CCT:C	acceptor_loss	1.0000

AlphaMissense

5279 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6560768:C:G	R456P	0.999
12:6561671:G:C	S400R	0.999
12:6561671:G:T	S400R	0.999
12:6561673:T:G	S400R	0.999
12:6561913:A:G	L346P	0.999
12:6561929:A:G	W341R	0.999
12:6561929:A:T	W341R	0.999
12:6561958:C:G	R331P	0.999
12:6561967:A:G	L328P	0.999
12:6563114:A:C	N315K	0.999
12:6563114:A:T	N315K	0.999
12:6561752:G:C	S373R	0.998
12:6561752:G:T	S373R	0.998
12:6561754:T:G	S373R	0.998
12:6561780:C:T	G364E	0.998
12:6561781:C:A	G364W	0.998
12:6561946:A:G	L335P	0.998
12:6563088:A:G	L324P	0.998
12:6560142:G:T	A582D	0.997
12:6560143:C:G	A582P	0.997
12:6560315:A:C	N524K	0.997
12:6560315:A:T	N524K	0.997
12:6560707:C:A	K476N	0.997
12:6560707:C:G	K476N	0.997
12:6560746:G:C	C463W	0.997
12:6560753:G:T	A461D	0.997
12:6560986:C:G	R431P	0.997
12:6561705:A:G	L389P	0.997
12:6561780:C:A	G364V	0.997
12:6561784:C:G	A363P	0.997

dbSNP variants (sampled 300 via entrez): RS1000279459 (12:6569555 C>A), RS1000398238 (12:6556824 T>TA), RS1000864902 (12:6564513 C>T), RS1000897756 (12:6558060 G>C), RS1001029468 (12:6564318 A>G), RS1001233336 (12:6564631 G>A,T), RS1001314043 (12:6561262 G>A), RS1001370697 (12:6569923 C>G), RS1002430986 (12:6561920 T>C), RS1002598458 (12:6562221 C>T), RS1002693422 (12:6558566 C>T), RS1002749830 (12:6570178 A>T), RS1002876704 (12:6561579 C>G,T), RS1002878363 (12:6558769 C>T), RS1003003276 (12:6570227 A>C,G)

Disease associations

OMIM: gene MIM:164031 | 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: yes

ChEMBL targets (1): CHEMBL6066899 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.69	Kd	0.204	nM	CHEMBL3752910
9.69	ED50	0.204	nM	CHEMBL3752910
6.44	Kd	366.3	nM	CHEMBL5653589
6.44	ED50	366.3	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148882: Binding affinity to human NOP2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0002	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148882: Binding affinity to human NOP2 incubated for 45 mins by Kinobead based pull down assay	kd	0.3663	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases methylation	3
Cadmium Chloride	decreases expression, increases expression	3
Estradiol	increases expression	2
Nickel	increases expression	2
Valproic Acid	affects expression, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	increases expression	1
alpha phellandrene	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651924	Binding	Binding affinity to human NOP2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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