RPS16

Summary

RPS16 (ribosomal protein S16, HGNC:10396) is a protein-coding gene on chromosome 19q13.2, encoding Small ribosomal subunit protein uS9 (P62249). Component of the small ribosomal subunit. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S9P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6217 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 22 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001020

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10396
Approved symbol	RPS16
Name	ribosomal protein S16
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	S16, uS9
Ensembl gene	ENSG00000105193
Ensembl biotype	protein_coding
OMIM	603675
Entrez	6217

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 22 protein_coding, 2 retained_intron

ENST00000251453, ENST00000339471, ENST00000595386, ENST00000599539, ENST00000599705, ENST00000601390, ENST00000601655, ENST00000602153, ENST00000870286, ENST00000870287, ENST00000912429, ENST00000912430, ENST00000912431, ENST00000912432, ENST00000912433, ENST00000912434, ENST00000912435, ENST00000912436, ENST00000912437, ENST00000912438, ENST00000912439, ENST00000912440, ENST00000912441, ENST00000912442

RefSeq mRNA: 3 — MANE Select: NM_001020 NM_001020, NM_001321111, NM_001363860

CCDS: CCDS12535, CCDS82349, CCDS86768

Canonical transcript exons

ENST00000251453 — 5 exons

Exon	Start	End
ENSE00000706039	39433665	39433761
ENSE00000877712	39435607	39435708
ENSE00003519164	39433137	39433418
ENSE00003575561	39433522	39433569
ENSE00003642476	39435848	39435949

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 857.1456 / max 6758.4432, expressed in 1828 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180887	798.7295	1828
180886	54.0981	1813
180885	1.7662	972
180884	1.5103	896
180882	0.5634	289
180883	0.4780	239

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	99.99	gold quality
adult organism	UBERON:0007023	99.99	gold quality
germinal epithelium of ovary	UBERON:0001304	99.98	gold quality
superficial temporal artery	UBERON:0001614	99.98	gold quality
parietal pleura	UBERON:0002400	99.98	gold quality
visceral pleura	UBERON:0002401	99.98	gold quality
pleura	UBERON:0000977	99.97	gold quality
skin of hip	UBERON:0001554	99.97	gold quality
nipple	UBERON:0002030	99.97	gold quality
upper leg skin	UBERON:0004262	99.97	gold quality
urethra	UBERON:0000057	99.96	gold quality
tibia	UBERON:0000979	99.96	gold quality
mammalian vulva	UBERON:0000997	99.96	gold quality
cardia of stomach	UBERON:0001162	99.96	gold quality
pylorus	UBERON:0001166	99.96	gold quality
pericardium	UBERON:0002407	99.96	gold quality
lower lobe of lung	UBERON:0008949	99.96	gold quality
oral cavity	UBERON:0000167	99.95	gold quality
renal medulla	UBERON:0000362	99.95	gold quality
penis	UBERON:0000989	99.95	gold quality
seminal vesicle	UBERON:0000998	99.95	gold quality
heart right ventricle	UBERON:0002080	99.95	gold quality
synovial joint	UBERON:0002217	99.95	gold quality
vena cava	UBERON:0004087	99.95	gold quality
saphenous vein	UBERON:0007318	99.95	gold quality
jejunal mucosa	UBERON:0000399	99.94	gold quality
pigmented layer of retina	UBERON:0001782	99.94	gold quality
gingival epithelium	UBERON:0001949	99.94	gold quality
trabecular bone tissue	UBERON:0002483	99.94	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.94	gold quality

Single-cell (SCXA)

Detected in 39 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	4579.28
E-CURD-122	yes	92.25
E-CURD-88	yes	64.77
E-MTAB-6678	yes	37.07
E-CURD-112	yes	36.39
E-HCAD-13	yes	25.67
E-HCAD-31	yes	24.26
E-MTAB-10042	yes	15.53
E-HCAD-35	yes	9.86
E-MTAB-8495	no	5690.10
E-MTAB-10432	no	5354.64
E-CURD-53	no	4965.31
E-HCAD-23	no	4867.99
E-CURD-79	no	4534.99
E-MTAB-8381	no	4450.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

31 targeting RPS16, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-6882-5P	99.35	71.13	1206

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• RpS16 was shown to specifically bind to the transcript forming a stable complex with the apparent dissociation constant of (1.3 +/- 0.1) x 10(-8) M at 20 degrees C. (PMID:18318121)
• Data demonstrated that while ribosomal proteins S16 and S5 is able to bind to the 18S rRNA independently, their simultaneous binding has a noticeable synergetic effect. (PMID:19559069)
• Results obtained support the possibility of the autoregulation of rpS13 pre-mRNA splicing through feedback mechanism. (PMID:20198863)
• Report dysregulated expression of RPS16 in disc degeneration. (PMID:25893343)
• These data confirmed RPS16 and TNFSF10 as two direct targets of miR-7641, while gene expression study showed that a group of genes are also deregulated by miR-7641, including many ribosomal proteins that are frequently co-expressed with RPS16 in breast cancer. (PMID:28827731)
• USP1-dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells. (PMID:34154657)
• MicroRNA let-7 Suppresses Influenza A Virus Infection by Targeting RPS16 and Enhancing Type I Interferon Response. (PMID:35873150)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps16	ENSDARG00000045487
mus_musculus	Rps16	ENSMUSG00000037563
rattus_norvegicus	Rps16l1	ENSRNOG00000030143
rattus_norvegicus	AABR07019341.1	ENSRNOG00000031960
drosophila_melanogaster	RpS16	FBGN0034743
caenorhabditis_elegans		WBGENE00004485

Paralogs (1): MRPS9 (ENSG00000135972)

Protein

Protein identifiers

Small ribosomal subunit protein uS9 — P62249 (reviewed: P62249)

Alternative names: 40S ribosomal protein S16

All UniProt accessions (6): P62249, M0QX76, M0R1M5, M0R210, M0R3H0, Q6IPX4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.

Subunit / interactions. Component of the small ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Similarity. Belongs to the universal ribosomal protein uS9 family.

RefSeq proteins (3): NP_001011, NP_001308040, NP_001350789 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000754	Ribosomal_uS9	Family
IPR014721	Ribsml_uS5_D2-typ_fold_subgr	Homologous_superfamily
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR020574	Ribosomal_uS9_CS	Conserved_site

Pfam: PF00380

UniProt features (16 total): helix 6, strand 5, modified residue 2, initiator methionine 1, chain 1, turn 1

Structure

Experimental structures (PDB)

212 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8GLP	ELECTRON MICROSCOPY	1.67
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
7R4X	ELECTRON MICROSCOPY	2.15
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8YOP	ELECTRON MICROSCOPY	2.2
9O3V	ELECTRON MICROSCOPY	2.2
9O3Y	ELECTRON MICROSCOPY	2.2
8JDK	ELECTRON MICROSCOPY	2.26
8G5Y	ELECTRON MICROSCOPY	2.29
9S3D	ELECTRON MICROSCOPY	2.32
9RPV	ELECTRON MICROSCOPY	2.35
9S3B	ELECTRON MICROSCOPY	2.38
8K2C	ELECTRON MICROSCOPY	2.4
8XSX	ELECTRON MICROSCOPY	2.4
9SPF	ELECTRON MICROSCOPY	2.4
9SPI	ELECTRON MICROSCOPY	2.4
8JDL	ELECTRON MICROSCOPY	2.42
9S3C	ELECTRON MICROSCOPY	2.42
9QLO	ELECTRON MICROSCOPY	2.47
9P8B	ELECTRON MICROSCOPY	2.48
7XNY	ELECTRON MICROSCOPY	2.5
8JDJ	ELECTRON MICROSCOPY	2.5
9RUC	ELECTRON MICROSCOPY	2.5
8G60	ELECTRON MICROSCOPY	2.54
8IFE	ELECTRON MICROSCOPY	2.57
9P7D	ELECTRON MICROSCOPY	2.57

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62249-F1	93.99	0.94

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 (2): 3, 60

Function

Pathways and Gene Ontology

Reactome pathways

50 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-156902	Peptide chain elongation
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-192823	Viral mRNA Translation
R-HSA-2408557	Selenocysteine synthesis
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72649	Translation initiation complex formation
R-HSA-72689	Formation of a pool of free 40S subunits
R-HSA-72695	Formation of the ternary complex, and subsequently, the 43S complex
R-HSA-72702	Ribosomal scanning and start codon recognition
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-72764	Eukaryotic Translation Termination
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-9735869	SARS-CoV-1 modulates host translation machinery
R-HSA-9754678	SARS-CoV-2 modulates host translation machinery
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-9954714	PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-156842	Eukaryotic Translation Elongation
R-HSA-1643685	Disease
R-HSA-168255	Influenza Infection
R-HSA-168273	Influenza Viral RNA Transcription and Replication
R-HSA-2262752	Cellular responses to stress
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-376176	Signaling by ROBO receptors
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 259 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, GOBP_RESPONSE_TO_PEPTIDE, MODULE_151, GCM_NPM1, GOBP_MATURATION_OF_SSU_RRNA, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, HSIAO_HOUSEKEEPING_GENES, PATIL_LIVER_CANCER, GOBP_TRANSLATION, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME

GO Biological Process (6): maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462), cytoplasmic translation (GO:0002181), rRNA processing (GO:0006364), translation (GO:0006412), ribosomal small subunit biogenesis (GO:0042274), cellular response to leukemia inhibitory factor (GO:1990830)

GO Molecular Function (3): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (15): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), small ribosomal subunit (GO:0015935), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), small-subunit processome (GO:0032040), synapse (GO:0045202), extracellular exosome (GO:0070062), nucleus (GO:0005634), nucleolus (GO:0005730), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Translation	2
Nonsense-Mediated Decay (NMD)	2
Ribosome-associated quality control	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	1
rRNA processing in the nucleus and cytosol	1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1
Signaling by ROBO receptors	1
Cellular response to starvation	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
ribosome biogenesis	2
ribosome	2
nuclear lumen	2
intracellular membraneless organelle	2
maturation of SSU-rRNA	1
translation	1
RNA processing	1
rRNA metabolic process	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
ribonucleoprotein complex biogenesis	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
nucleic acid binding	1
structural molecule activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
ribosomal subunit	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
cell junction	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

280 interactions, top by confidence:

A	B	Type	Score
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RPS19	RPS16	psi-mi:“MI:0915”(physical association)	0.670
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
E4F1	ZBTB24	psi-mi:“MI:0914”(association)	0.530
RPF1	ZNF324	psi-mi:“MI:0914”(association)	0.530
BHLHA15	RPLP0	psi-mi:“MI:0914”(association)	0.530
RBM8A	RPS16	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
WDR4	PCNA	psi-mi:“MI:0914”(association)	0.460
ESR1		psi-mi:“MI:0914”(association)	0.460
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430
NDRG1	RPS16	psi-mi:“MI:0915”(physical association)	0.400
C1orf87	RPS16	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1202): RPS16 (Affinity Capture-MS), RPS16 (Affinity Capture-MS), RPS16 (Affinity Capture-MS), ATP6V0D1 (Co-fractionation), FAU (Co-fractionation), RPL10A (Co-fractionation), RPL12 (Co-fractionation), RPL13 (Co-fractionation), RPL13A (Co-fractionation), RPL18 (Co-fractionation), RPL18A (Co-fractionation), RPL21 (Co-fractionation), RPL23 (Co-fractionation), RPL24 (Co-fractionation), RPL27 (Co-fractionation)

ESM2 similar proteins: A2YDY2, A5PK63, A8D8X1, A9CB60, B7NZQ2, G1SGX4, G1TG89, G1TU13, P02362, P04644, P05388, P08636, P08708, P14131, P14869, P19945, P27635, P42794, P42795, P46287, P50894, P62084, P62244, P62245, P62246, P62249, P62250, P63273, P63274, P63275, P63276, P86048, Q0DK10, Q29195, Q29201, Q2TBW8, Q3T0X6, Q4R7Y2, Q5R931, Q5R938

Diamond homologs: A0A1D8PCW6, A0B6E8, A0LIV3, A0LXM9, A1BHZ6, A1VBD2, A2ZB00, A4FWK9, A6GWU3, A6UPX0, A6UW00, A6VGR2, A9BHB5, B2SYK9, B2URR4, B3E0U1, B3EFY3, B3PBL9, B4SEC8, B5Z683, B6JPI5, B6YQS6, B8D6F5, B8DPL8, B8IZP3, C4XNQ1, C6A1B6, C6C1K0, G1SGX4, O22647, O26146, O29136, O59299, O94017, P05763, P0CT64, P0CT65, P0CX51, P0CX52, P14131

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS16	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 216 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
TRAF6 mediated NF-kB activation	6	18.0×	3e-05
SRP-dependent cotranslational protein targeting to membrane	23	15.2×	3e-18
Formation of a pool of free 40S subunits	20	14.7×	5e-16
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	19	14.7×	2e-15
GTP hydrolysis and joining of the 60S ribosomal subunit	22	14.5×	3e-17
Eukaryotic Translation Termination	18	14.2×	3e-14
Peptide chain elongation	17	14.2×	1e-13
Viral mRNA Translation	17	14.2×	1e-13

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	5	29.7×	7e-05
cytoplasmic translation	20	19.6×	2e-17
translational initiation	8	15.2×	2e-05
ribosomal large subunit biogenesis	6	14.1×	4e-04
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	12.4×	3e-03
regulation of translational initiation	5	12.4×	3e-03
mitophagy	7	11.8×	3e-04
canonical NF-kappaB signal transduction	6	11.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

646 predictions. Top by Δscore:

Variant	Effect	Δscore
19:39433414:CACAT:C	acceptor_gain	1.0000
19:39433415:ACAT:A	acceptor_gain	1.0000
19:39433416:CAT:C	acceptor_gain	1.0000
19:39433416:CATC:C	acceptor_gain	1.0000
19:39433417:AT:A	acceptor_gain	1.0000
19:39433417:ATCT:A	acceptor_loss	1.0000
19:39433418:TCTG:T	acceptor_loss	1.0000
19:39433419:C:CC	acceptor_gain	1.0000
19:39433419:CTG:C	acceptor_loss	1.0000
19:39433420:T:C	acceptor_loss	1.0000
19:39433423:C:CT	acceptor_gain	1.0000
19:39433424:A:T	acceptor_gain	1.0000
19:39433432:C:CT	acceptor_gain	1.0000
19:39433516:A:AC	donor_gain	1.0000
19:39433517:C:CC	donor_gain	1.0000
19:39433517:CT:C	donor_gain	1.0000
19:39433517:CTCA:C	donor_gain	1.0000
19:39433519:CACA:C	donor_loss	1.0000
19:39433520:A:AC	donor_gain	1.0000
19:39433521:C:CA	donor_gain	1.0000
19:39433521:CA:C	donor_gain	1.0000
19:39433521:CATTT:C	donor_gain	1.0000
19:39433567:TAG:T	acceptor_gain	1.0000
19:39433569:GC:G	acceptor_loss	1.0000
19:39433570:C:CC	acceptor_gain	1.0000
19:39433571:T:C	acceptor_loss	1.0000
19:39433660:CTCA:C	donor_loss	1.0000
19:39433661:TCA:T	donor_loss	1.0000
19:39433662:CACC:C	donor_loss	1.0000
19:39433663:A:AC	donor_gain	1.0000

AlphaMissense

922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:39433318:A:C	F132L	0.999
19:39433318:A:T	F132L	0.999
19:39433320:A:G	F132L	0.999
19:39433288:C:A	Q142H	0.998
19:39433288:C:G	Q142H	0.998
19:39433316:C:T	G133E	0.998
19:39433703:A:T	V70D	0.998
19:39435682:G:C	C25W	0.998
19:39435684:A:G	C25R	0.998
19:39435695:G:T	A21D	0.998
19:39435696:C:G	A21P	0.998
19:39435701:G:T	A19E	0.998
19:39435702:C:G	A19P	0.998
19:39435855:C:T	G14E	0.998
19:39435857:G:C	F13L	0.998
19:39435857:G:T	F13L	0.998
19:39435859:A:G	F13L	0.998
19:39433313:C:T	G134D	0.997
19:39433324:T:A	K130N	0.997
19:39433324:T:G	K130N	0.997
19:39433341:G:T	R125S	0.997
19:39433367:T:A	D116V	0.997
19:39433379:A:G	L112P	0.997
19:39433545:G:T	A91D	0.997
19:39433546:C:G	A91P	0.997
19:39433563:C:G	R85P	0.997
19:39433569:G:T	A83D	0.997
19:39435689:G:T	A23E	0.997
19:39435690:C:G	A23P	0.997
19:39433285:T:A	K143N	0.996

dbSNP variants (sampled 300 via entrez): RS1000541073 (19:39432704 G>T), RS1000701357 (19:39435118 G>A,C,T), RS1002093885 (19:39434961 A>C), RS1002549601 (19:39435256 G>A), RS1003326876 (19:39436280 C>T), RS1003600482 (19:39436553 C>T), RS1003810603 (19:39436079 G>A,C,T), RS1004836724 (19:39436693 C>G), RS1005681085 (19:39433186 A>C,G), RS1005735465 (19:39437907 A>T), RS1005772489 (19:39435815 T>C), RS1005838050 (19:39436936 A>G), RS1006122466 (19:39436552 T>C), RS1007361447 (19:39434109 C>G,T), RS1007795825 (19:39437687 G>A)

Disease associations

OMIM: gene MIM:603675 | 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 (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067569 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

51 potent at pChembl≥5 of 55 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	Kd	49.74	nM	CHEMBL3752910
7.30	ED50	49.74	nM	CHEMBL3752910
6.52	IC50	300	nM	CHEMBL4109308
6.46	Kd	344.9	nM	CHEMBL5653589
6.46	ED50	344.9	nM	CHEMBL5653589
6.42	IC50	380	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4574496
6.41	IC50	390	nM	CHEMBL4126894
6.39	IC50	410	nM	CHEMBL4114159
6.35	IC50	450	nM	CHEMBL4126496
6.30	IC50	500	nM	CHEMBL4574496
6.30	IC50	500	nM	CHEMBL4560206
6.16	IC50	690	nM	CHEMBL4130157
6.15	IC50	710	nM	CHEMBL4108338
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	IC50	900	nM	CHEMBL4126894
6.05	IC50	900	nM	CHEMBL4126496
6.04	IC50	920	nM	CHEMBL4554909
5.97	IC50	1060	nM	CHEMBL4128388
5.89	IC50	1290	nM	CHEMBL4130157
5.86	IC50	1370	nM	CHEMBL4107559
5.84	IC50	1440	nM	CHEMBL4108338
5.81	IC50	1540	nM	CHEMBL4534859
5.76	IC50	1730	nM	CHEMBL4534859
5.69	IC50	2050	nM	CHEMBL4566239
5.68	IC50	2080	nM	CHEMBL4446635
5.66	IC50	2210	nM	CHEMBL4446635
5.66	EC50	2200	nM	CHEMBL4464929
5.64	IC50	2270	nM	CHEMBL4533299
5.63	IC50	2330	nM	CHEMBL4566239
5.62	IC50	2380	nM	CHEMBL4128388
5.58	IC50	2630	nM	CHEMBL4128250
5.55	IC50	2820	nM	CHEMBL4127458
5.53	IC50	2970	nM	CHEMBL4127311
5.51	IC50	3080	nM	CHEMBL4126072
5.46	IC50	3500	nM	CHEMBL4525277
5.44	IC50	3630	nM	CHEMBL4469712
5.39	IC50	4100	nM	CHEMBL4128560
5.37	IC50	4300	nM	CHEMBL4127016
5.36	IC50	4380	nM	CHEMBL4527910
5.36	IC50	4410	nM	MOLIBRESIB
5.16	IC50	7000	nM	CHEMBL4109308
5.13	IC50	7400	nM	CHLORAMPHENICOL SULFATE SALT
5.09	IC50	8040	nM	CHEMBL4128250
5.08	IC50	8370	nM	CHEMBL4128250
5.03	IC50	9320	nM	CHEMBL4127016
5.03	IC50	9240	nM	CHEMBL4128560

PubChem BioAssay actives

49 with measured affinity, of 215 total; 29 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	2149289: Binding affinity to human RPS16 incubated for 45 mins by Kinobead based pull down assay	kd	0.0497	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1585498: Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method	ic50	0.3000	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149289: Binding affinity to human RPS16 incubated for 45 mins by Kinobead based pull down assay	kd	0.3449	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-3-[4-(triazolo[4,5-b]pyridin-3-yl)phenyl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3800	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3900	uM
N-(3-chloro-2-pyridinyl)-4-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4100	uM
N-(3-chloro-2-pyridinyl)-4-(5-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4500	uM
N-(1-methylpyrrolo[2,3-c]pyridin-7-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.5000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.6900	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-5-(triazolo[4,5-b]pyridin-3-yl)pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.7100	uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylpiperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.9200	uM
N-isoquinolin-1-yl-4-(1-methylpyrazol-4-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	1.0600	uM
N-isoquinolin-1-yl-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	1.5400	uM
N-(3-methyl-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.0500	uM
N-(3-chloro-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	2.0800	uM
N-(5,8-dihydroisoquinolin-1-yl)-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1584424: Inhibition of human 80S ribosome-mediated PCSK9 translation expressed in CHO-K1 cells assessed as reduction in PCSK9 secretion	ec50	2.2000	uM
N-isoquinolin-1-yl-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.6300	uM
N-(3-chloro-2-pyridinyl)-4-(6-methylpyrazin-2-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.8200	uM
N-(3-chloro-2-pyridinyl)-4-[6-(dimethylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.9700	uM
N-(3-chloro-2-pyridinyl)-4-[6-(methylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	3.0800	uM
N-isoquinolin-1-yl-4-(6-methyl-1,2-benzoxazol-3-yl)-N-[(3R)-piperidin-3-yl]piperazine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	3.5000	uM
N-(3-methylpyrazin-2-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	3.6300	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-6-(triazolo[4,5-b]pyridin-3-yl)pyridine-3-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.1000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazin-2-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.3000	uM
4-(2-fluorophenyl)-N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	4.3800	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178980: Inhibition of RPS16 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	4.4100	uM
2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide;sulfuric acid	717551: Inhibition of mitochondrial ribosome-mediated protein synthesis in human HeLa cells assessed as {35S]methionine incorporation by autoradiography	ic50	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	2
sodium arsenite	increases activity, increases abundance, increases expression, decreases expression	2
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
tetrabromobisphenol A	decreases expression	1
CD 437	decreases expression	1
chloropicrin	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
Grape Seed Proanthocyanidins	increases expression, affects cotreatment	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Arsenic	increases abundance, increases expression	1
Aspirin	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	decreases expression	1

ChEMBL screening assays

96 unique, capped per target: 96 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1920845	Binding	Induction of ribosome to readthrough in human A-T lymphoblastoid cells assessed as ATM ser1981 autophosphorylation at 30 uM after 4 days by PTT-ELISA assay	Synthesis and evaluation of compounds that induce readthrough of premature termination codons. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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