NOP16

Summary

NOP16 (NOP16 nucleolar protein, HGNC:26934) is a protein-coding gene on chromosome 5q35.2, encoding Nucleolar protein 16 (Q9Y3C1). It is a common-essential gene (DepMap: required in 99.2% of cancer cell lines).

This gene encodes a protein that is localized to the nucleolus. Expression of this gene is induced by estrogens and Myc protein and is a marker of poor patient survival in breast cancer. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51491 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• Cancer dependency (DepMap): dependent in 99.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_016391

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26934
Approved symbol	NOP16
Name	NOP16 nucleolar protein
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Aliases	HSPC111, HSPC185, LOC51491
Ensembl gene	ENSG00000048162
Ensembl biotype	protein_coding
OMIM	612861
Entrez	51491

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000502577, ENST00000502663, ENST00000503849, ENST00000504821, ENST00000509257, ENST00000510608, ENST00000614830, ENST00000616685, ENST00000618911, ENST00000621444, ENST00000860843, ENST00000935388, ENST00000935389, ENST00000935390, ENST00000935391, ENST00000935392, ENST00000935393

RefSeq mRNA: 7 — MANE Select: NM_016391 NM_001256539, NM_001256540, NM_001291305, NM_001291307, NM_001291308, NM_001317975, NM_016391

CCDS: CCDS43403, CCDS58991, CCDS78091

Canonical transcript exons

ENST00000614830 — 5 exons

Exon	Start	End
ENSE00003482207	176386840	176386909
ENSE00003566971	176388235	176388343
ENSE00003724637	176388433	176388598
ENSE00003726100	176385221	176385327
ENSE00003735499	176383946	176384374

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 95.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.4794 / max 356.0481, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64998	47.6229	1818
64999	0.8565	500

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	95.49	gold quality
lower esophagus mucosa	UBERON:0035834	94.91	gold quality
muscle of leg	UBERON:0001383	94.49	gold quality
mucosa of transverse colon	UBERON:0004991	94.33	gold quality
esophagus mucosa	UBERON:0002469	94.20	gold quality
skin of abdomen	UBERON:0001416	92.82	gold quality
muscle organ	UBERON:0001630	92.65	gold quality
gingival epithelium	UBERON:0001949	92.65	gold quality
esophagus	UBERON:0001043	92.60	gold quality
skin of leg	UBERON:0001511	92.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.10	gold quality
left uterine tube	UBERON:0001303	92.05	gold quality
omental fat pad	UBERON:0010414	91.73	gold quality
peritoneum	UBERON:0002358	91.71	gold quality
right atrium auricular region	UBERON:0006631	91.69	gold quality
granulocyte	CL:0000094	91.68	gold quality
gingiva	UBERON:0001828	91.66	gold quality
heart left ventricle	UBERON:0002084	91.46	gold quality
zone of skin	UBERON:0000014	91.22	gold quality
cardiac ventricle	UBERON:0002082	91.13	gold quality
transverse colon	UBERON:0001157	91.11	gold quality
lower esophagus	UBERON:0013473	91.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.06	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.87	gold quality
body of stomach	UBERON:0001161	90.72	gold quality
cardiac atrium	UBERON:0002081	90.52	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.41	gold quality
right lobe of liver	UBERON:0001114	90.27	gold quality
triceps brachii	UBERON:0001509	90.23	gold quality
gluteal muscle	UBERON:0002000	90.23	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	1147.18
E-MTAB-9543	yes	14.97
E-MTAB-6819	no	378.33
E-HCAD-13	no	3.40
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

13 targeting NOP16, 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-6867-5P	100.00	82.21	3464
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• HSPC111 is an estrogen and c-Myc target gene that is over-expressed in breast cancer and is associated with an adverse patient outcome. (PMID:18373870)
• RNA 3’-phosphate cyclase (RTCD1/RTCA) interacted with HSPC111, and RTCD1 was involved in the HSPC111 multiprotein complex in regulating rRNA production and ribosomal biogenesis. (PMID:24425784)
• Cancer-derived exosomal HSPC111 promotes colorectal cancer liver metastasis by reprogramming lipid metabolism in cancer-associated fibroblasts. (PMID:35027547)
• Elevated Expression of NOP16 as a Novel Prognostic Biomarker of Prostate Cancer. (PMID:37625836)
• NOP16 promotes hepatocellular carcinoma progression and triggers EMT through the Keap1-Nrf2 signaling pathway. (PMID:38251077)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nop16	ENSDARG00000044402
mus_musculus	Nop16	ENSMUSG00000025869
rattus_norvegicus	Nop16	ENSRNOG00000017284
drosophila_melanogaster	CG11563	FBGN0039868
caenorhabditis_elegans	nol-16	WBGENE00013958

Protein

Protein identifiers

Nucleolar protein 16 — Q9Y3C1 (reviewed: Q9Y3C1)

Alternative names: HBV pre-S2 trans-regulated protein 3

All UniProt accessions (5): A0A087WU10, A0A0C4DGU5, D6RC60, D6RIC3, Q9Y3C1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus. Nucleolus.

Similarity. Belongs to the NOP16 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y3C1-1	1	yes
Q9Y3C1-2	2
Q9Y3C1-3	3

RefSeq proteins (7): NP_001243468, NP_001243469, NP_001278234, NP_001278236, NP_001278237, NP_001304904, NP_057475* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019002	Ribosome_biogenesis_Nop16	Family

Pfam: PF09420

UniProt features (16 total): cross-link 5, modified residue 4, sequence conflict 3, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

10 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
8FKQ	ELECTRON MICROSCOPY	2.76
8FKT	ELECTRON MICROSCOPY	2.81
8FKU	ELECTRON MICROSCOPY	2.82
8FKP	ELECTRON MICROSCOPY	2.85
8FKS	ELECTRON MICROSCOPY	2.88
8FKR	ELECTRON MICROSCOPY	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3C1-F1	85.68	0.56

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 (9): 166, 172, 167, 173, 8, 16, 90, 144, 74

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 244 (showing top): GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, BASSO_B_LYMPHOCYTE_NETWORK, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, GENTILE_UV_HIGH_DOSE_DN, FUNG_IL2_SIGNALING_1, DODD_NASOPHARYNGEAL_CARCINOMA_UP, BROWN_MYELOID_CELL_DEVELOPMENT_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, HAN_SATB1_TARGETS_DN, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_RIBOSOMAL_LARGE_SUBUNIT_BIOGENESIS, BERENJENO_TRANSFORMED_BY_RHOA_UP

GO Biological Process (1): ribosomal large subunit biogenesis (GO:0042273)

GO Molecular Function (1): RNA binding (GO:0003723)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
nucleic acid binding	1
cellular anatomical structure	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOP16	FBL	P22087	664
NOP16	ARL10	Q8N8L6	607
NOP16	RPS10	P46783	498
NOP16	RPL5	P46777	481
NOP16	RPS17	P08708	470
NOP16	ZNF593	O00488	462
NOP16	RPL11	P25121	456
NOP16	CRYBG2	Q8N1P7	455
NOP16	MYC	P01106	452
NOP16	NCAPG2	Q86XI2	449
NOP16	CD34	P28906	426
NOP16	HIGD2A	Q9BW72	419
NOP16	ESR1	P03372	412
NOP16	SIMC1	Q8NDZ2	399
NOP16	DDX27	Q96GQ7	399

IntAct

166 interactions, top by confidence:

A	B	Type	Score
STK3	RASSF2	psi-mi:“MI:0914”(association)	0.950
N	HNRNPR	psi-mi:“MI:0914”(association)	0.730
NPM1	NVL	psi-mi:“MI:0914”(association)	0.610
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
BHLHA15	RPLP0	psi-mi:“MI:0914”(association)	0.530
NOP16	NAP1L1	psi-mi:“MI:0914”(association)	0.530
WDR48	USP12	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
ZC3HAV1	KHNYN	psi-mi:“MI:0914”(association)	0.530
CLEC3A	ZZEF1	psi-mi:“MI:0914”(association)	0.530
H1-4	RRP8	psi-mi:“MI:0914”(association)	0.530
MRPL18	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
NOP16	IPO5	psi-mi:“MI:0914”(association)	0.530
KRR1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
NAP1L1	H2AC11	psi-mi:“MI:0914”(association)	0.530
BHLHA15	YBX3	psi-mi:“MI:0914”(association)	0.530
NOP16	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SRPK1	NOP16	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PRPF38B	NOP16	psi-mi:“MI:0915”(physical association)	0.400
CERK	NOP16	psi-mi:“MI:0915”(physical association)	0.400
Srp72		psi-mi:“MI:0914”(association)	0.350
NOP56	C12orf43	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
OAS3	PTBP1	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
P2RY6	RAVER1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (237): NOP16 (Affinity Capture-MS), NOP16 (Affinity Capture-MS), NOP16 (Affinity Capture-MS), NOP16 (Affinity Capture-MS), NOP16 (Affinity Capture-MS), NOP16 (Reconstituted Complex), NOP16 (Affinity Capture-MS), NOP16 (Affinity Capture-MS), NOP16 (Affinity Capture-MS), NOP16 (Affinity Capture-MS), NOP16 (Affinity Capture-MS), HERC5 (Affinity Capture-MS), NOP16 (Affinity Capture-MS), NAP1L1 (Affinity Capture-MS), NOP16 (Affinity Capture-MS)

ESM2 similar proteins: A1CFJ6, A1CYJ1, A2QGZ1, A3LU29, A4IGY3, A4R9U5, A5DFT1, A5DYR5, A6RC73, A6RNR4, A6ZQU8, A7E664, A7TP28, B0UYI1, O08837, O60870, P0CP24, P0CP25, P27088, P40007, Q0CDP3, Q0UBQ5, Q1EBC4, Q1RP77, Q2KIA6, Q2KJC1, Q3TIV5, Q4SQ06, Q4WIK9, Q59YD8, Q5AVK6, Q5E996, Q5H7N8, Q64267, Q6A068, Q6BWR0, Q6DD06, Q6DGI3, Q6GP80, Q6NVB0

Diamond homologs: Q1RP77, Q4SQ06, Q5E996, Q6DGI3, Q6GP80, Q6NVB0, Q94402, Q9CPT5, Q9Y3C1, Q6CQW3, Q76IQ1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 191 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
Peptide chain elongation	17	16.3×	2e-14
Viral mRNA Translation	17	16.3×	2e-14
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	17	16.2×	2e-14
Selenocysteine synthesis	17	15.5×	3e-14
Eukaryotic Translation Termination	17	15.5×	3e-14
Formation of a pool of free 40S subunits	18	15.3×	1e-14
SRP-dependent cotranslational protein targeting to membrane	20	15.2×	8e-16
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	17	15.2×	3e-14

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	7	30.5×	4e-07
cytoplasmic translation	20	21.0×	3e-18
ribosomal large subunit biogenesis	6	15.1×	2e-04
negative regulation of viral genome replication	7	14.9×	5e-05
translation	23	13.4×	6e-17
ribosomal small subunit biogenesis	10	12.9×	9e-07
regulation of alternative mRNA splicing, via spliceosome	9	12.5×	6e-06
rRNA processing	15	12.1×	5e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

912 predictions. Top by Δscore:

Variant	Effect	Δscore
5:176384371:TGGC:T	acceptor_gain	1.0000
5:176384374:CCTA:C	acceptor_loss	1.0000
5:176384375:C:CC	acceptor_gain	1.0000
5:176384375:CTA:C	acceptor_loss	1.0000
5:176385215:GCTCA:G	donor_loss	1.0000
5:176385217:TCAC:T	donor_loss	1.0000
5:176385220:C:G	donor_loss	1.0000
5:176385323:CAGGT:C	acceptor_gain	1.0000
5:176385324:AGGT:A	acceptor_gain	1.0000
5:176385325:GGT:G	acceptor_gain	1.0000
5:176385326:GT:G	acceptor_gain	1.0000
5:176385328:C:CA	acceptor_loss	1.0000
5:176385328:C:CC	acceptor_gain	1.0000
5:176385333:G:C	acceptor_gain	1.0000
5:176385333:G:GC	acceptor_gain	1.0000
5:176385336:A:AC	acceptor_gain	1.0000
5:176385336:A:C	acceptor_gain	1.0000
5:176385346:C:CT	acceptor_gain	1.0000
5:176384370:ATGGC:A	acceptor_gain	0.9900
5:176384372:GGC:G	acceptor_gain	0.9900
5:176384373:GC:G	acceptor_gain	0.9900
5:176384374:CC:C	acceptor_gain	0.9900
5:176384376:T:G	acceptor_loss	0.9900
5:176385347:G:T	acceptor_gain	0.9900
5:176388455:T:TA	donor_gain	0.9900
5:176385219:A:AC	donor_gain	0.9800
5:176385220:C:CC	donor_gain	0.9800
5:176385243:TC:T	donor_gain	0.9800
5:176385244:C:CT	donor_gain	0.9800
5:176385245:T:TT	donor_gain	0.9800

AlphaMissense

1173 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:176384351:A:C	N139K	0.999
5:176384351:A:T	N139K	0.999
5:176384342:T:A	Q142H	0.997
5:176384342:T:G	Q142H	0.997
5:176388322:C:A	W43C	0.997
5:176388322:C:G	W43C	0.997
5:176388324:A:G	W43R	0.997
5:176388324:A:T	W43R	0.997
5:176388278:A:G	L58S	0.996
5:176384367:G:T	A134D	0.995
5:176384368:C:G	A134P	0.995
5:176388501:A:C	F13L	0.995
5:176388501:A:T	F13L	0.995
5:176388503:A:G	F13L	0.995
5:176384325:A:C	I148S	0.994
5:176384325:A:G	I148T	0.994
5:176384353:T:C	N139D	0.994
5:176384369:C:A	M133I	0.994
5:176384369:C:G	M133I	0.994
5:176384369:C:T	M133I	0.994
5:176388293:A:G	L53P	0.993
5:176384353:T:G	N139H	0.992
5:176385313:C:G	A101P	0.992
5:176388282:C:A	G57W	0.992
5:176384352:T:A	N139I	0.991
5:176388282:C:G	G57R	0.991
5:176388282:C:T	G57R	0.991
5:176388295:G:C	N52K	0.991
5:176388295:G:T	N52K	0.991
5:176388323:C:G	W43S	0.991

dbSNP variants (sampled 300 via entrez): RS1000108407 (5:176384619 T>G), RS1000459344 (5:176389670 T>C), RS1001320589 (5:176389600 C>T), RS1001629098 (5:176387265 A>G), RS1002462273 (5:176386761 A>C), RS1003075003 (5:176385780 G>A), RS1003098830 (5:176387027 A>T), RS1003724854 (5:176385415 C>T), RS10042045 (5:176385214 C>T), RS1004469296 (5:176383971 C>T), RS1004551807 (5:176388945 G>A,C,T), RS1005097758 (5:176390049 T>G), RS1005104678 (5:176390254 G>A), RS1005629082 (5:176389134 A>C), RS1005818842 (5:176387650 G>T)

Disease associations

OMIM: gene MIM:612861 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	5
bisphenol A	decreases reaction, increases abundance, affects expression, decreases expression	4
trichostatin A	affects expression, affects cotreatment, increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
cobaltous chloride	decreases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression, affects response to substance	2
Benzo(a)pyrene	increases expression, increases methylation	2
Tretinoin	decreases expression	2
Aflatoxin B1	affects cotreatment, decreases expression, increases expression, increases methylation	2
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
afuresertib	decreases expression	1
TAK-243	increases sumoylation	1
ginger extract	decreases expression, decreases reaction, increases abundance	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
nivalenol	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol S	affects expression	1
LDN 193189	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1

Clinical trials (associated diseases)

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