RPS9

Summary

RPS9 (ribosomal protein S9, HGNC:10442) is a protein-coding gene on chromosome 19q13.42, encoding Small ribosomal subunit protein uS4 (P46781). 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 S4P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome.

Source: NCBI Gene 6203 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 32 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001013

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10442
Approved symbol	RPS9
Name	ribosomal protein S9
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	S9, uS4
Ensembl gene	ENSG00000170889
Ensembl biotype	protein_coding
OMIM	603631
Entrez	6203

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 27 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000302907, ENST00000391751, ENST00000391752, ENST00000391753, ENST00000402367, ENST00000436445, ENST00000441429, ENST00000445961, ENST00000448962, ENST00000460761, ENST00000484121, ENST00000495002, ENST00000626547, ENST00000910926, ENST00000910927, ENST00000910928, ENST00000910929, ENST00000910930, ENST00000910931, ENST00000919246, ENST00000919247, ENST00000919248, ENST00000919249, ENST00000919250, ENST00000919251, ENST00000919252, ENST00000919253, ENST00000919254, ENST00000919255, ENST00000919256, ENST00000919257, ENST00000960920, ENST00000960921

RefSeq mRNA: 6 — MANE Select: NM_001013 NM_001013, NM_001321701, NM_001321702, NM_001321704, NM_001321705, NM_001321706

CCDS: CCDS12884, CCDS82397

Canonical transcript exons

ENST00000302907 — 5 exons

Exon	Start	End
ENSE00001276356	54206276	54206462
ENSE00001404574	54200858	54200888
ENSE00003649985	54207398	54207647
ENSE00003680529	54201160	54201281
ENSE00003692829	54201487	54201609

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 479.1673 / max 3247.5362, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
208925	469.5667	1827
177481	5.3589	1677
177480	2.1005	1192
177479	1.6000	992
177482	0.5412	304

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.88	gold quality
leukocyte	CL:0000738	99.87	gold quality
left ovary	UBERON:0002119	99.84	gold quality
ovary	UBERON:0000992	99.83	gold quality
right ovary	UBERON:0002118	99.83	gold quality
right uterine tube	UBERON:0001302	99.81	gold quality
zone of skin	UBERON:0000014	99.80	gold quality
lymph node	UBERON:0000029	99.80	gold quality
endocervix	UBERON:0000458	99.80	gold quality
skin of abdomen	UBERON:0001416	99.80	gold quality
skin of leg	UBERON:0001511	99.80	gold quality
vermiform appendix	UBERON:0001154	99.79	gold quality
fallopian tube	UBERON:0003889	99.79	gold quality
right lobe of thyroid gland	UBERON:0001119	99.78	gold quality
left adrenal gland	UBERON:0001234	99.78	gold quality
gall bladder	UBERON:0002110	99.78	gold quality
ganglionic eminence	UBERON:0004023	99.78	gold quality
thoracic mammary gland	UBERON:0005200	99.78	gold quality
metanephros cortex	UBERON:0010533	99.78	gold quality
left adrenal gland cortex	UBERON:0035825	99.78	gold quality
granulocyte	CL:0000094	99.77	gold quality
adipose tissue	UBERON:0001013	99.77	gold quality
body of pancreas	UBERON:0001150	99.77	gold quality
mucosa of stomach	UBERON:0001199	99.77	gold quality
mammary gland	UBERON:0001911	99.77	gold quality
spleen	UBERON:0002106	99.77	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.77	gold quality
prostate gland	UBERON:0002367	99.77	gold quality
body of uterus	UBERON:0009853	99.77	gold quality
left lobe of thyroid gland	UBERON:0001120	99.76	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-8	yes	1104.71
E-CURD-46	yes	57.75
E-HCAD-35	yes	8.74
E-HCAD-25	yes	4.57
E-MTAB-10596	no	3894.19
E-HCAD-6	no	1433.53
E-MTAB-10885	no	1107.55
E-GEOD-125970	no	1071.73
E-MTAB-10283	no	973.02
E-CURD-114	no	819.76
E-MTAB-8060	no	589.81
E-CURD-120	no	586.91
E-GEOD-110499	no	162.46
E-MTAB-6911	no	131.10
E-HCAD-1	no	95.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 7)

• B23 selectively stores, and protects ribosomal protein S9 in nucleoli and therefore could facilitate ribosome biogenesis. (PMID:18420587)
• ribosomal protein S9 silencing elicits a multitude of cellular responses inhibiting the growth of cancer cells subsequent to p53 activation (PMID:20221446)
• Evaluating different RPS9 fragments for their ability to bind NPM1 indicated that there are two binding sites for NPM1 on RPS9. (PMID:23285058)
• RPS9/LILRB3 (rs11666543) was associated with Takayasu arteritis. (PMID:25604533)
• Inhibition of RPS9 can promote apoptosis, cell cycle arrest, and proliferation of myeloma cells. RPS9 can affect the activation of NF-kappaB pathway and cell apoptosis through SENP1 (PMID:31060671)
• LncRNA BRCAT54 inhibits the tumorigenesis of non-small cell lung cancer by binding to RPS9 to transcriptionally regulate JAK-STAT and calcium pathway genes. (PMID:32459848)
• LAPTM4B promotes AML progression through regulating RPS9/STAT3 axis. (PMID:36758682)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps9	ENSDARG00000011405
mus_musculus	Rps9	ENSMUSG00000006333
rattus_norvegicus	LOC120097492	ENSRNOG00000050067
drosophila_melanogaster	RpS9	FBGN0010408
caenorhabditis_elegans		WBGENE00004478

Protein

Protein identifiers

Small ribosomal subunit protein uS4 — P46781 (reviewed: P46781)

Alternative names: 40S ribosomal protein S9

All UniProt accessions (5): P46781, A8MXK4, B5MCT8, C9JM19, F2Z3C0

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. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. 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 uS4 family.

RefSeq proteins (6): NP_001004, NP_001308630, NP_001308631, NP_001308633, NP_001308634, NP_001308635 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001912	Ribosomal_uS4_N	Domain
IPR002942	S4_RNA-bd	Domain
IPR005710	Ribosomal_uS4_euk_arc	Family
IPR018079	Ribosomal_uS4_CS	Conserved_site
IPR022801	Ribosomal_uS4	Family
IPR036986	S4_RNA-bd_sf	Homologous_superfamily

Pfam: PF00163, PF01479

UniProt features (31 total): helix 11, strand 6, modified residue 5, cross-link 2, sequence conflict 2, initiator methionine 1, chain 1, sequence variant 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

213 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-P46781-F1	88.90	0.76

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 (7): 139, 66, 116, 153, 155, 163, 93

Function

Pathways and Gene Ontology

Reactome pathways

51 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-6790901	rRNA modification in the nucleus and cytosol
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

MSigDB gene sets: 241 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, GRUETZMANN_PANCREATIC_CANCER_DN, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCM_NPM1, HSIAO_HOUSEKEEPING_GENES, GOBP_TRANSLATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, DIRMEIER_LMP1_RESPONSE_EARLY, CHNG_MULTIPLE_MYELOMA_HYPERPLOID_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, CUI_TCF21_TARGETS_2_UP

GO Biological Process (3): cytoplasmic translation (GO:0002181), ribosomal small subunit biogenesis (GO:0042274), translation (GO:0006412)

GO Molecular Function (4): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), rRNA binding (GO:0019843), protein binding (GO:0005515)

GO Cellular Component (15): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), ribosome (GO:0005840), focal adhesion (GO:0005925), 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), ribonucleoprotein complex (GO:1990904), small ribosomal subunit (GO:0015935)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Translation	2
rRNA processing in the nucleus and cytosol	2
Nonsense-Mediated Decay (NMD)	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	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
Ribosome-associated quality control	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
ribosome	2
nuclear lumen	2
intracellular membraneless organelle	2
translation	1
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	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
nucleic acid binding	1
structural molecule activity	1
RNA binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	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
protein-containing complex	1
ribosomal subunit	1

Protein interactions and networks

STRING

5207 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS9	RPS5	P46782	969
RPS9	RPL27A	P46776	957
RPS9	RPL5	P46777	954
RPS9	RPL21	P46778	953
RPS9	RPS10	P46783	946
RPS9	RPS29	P30054	943
RPS9	RPL28	P46779	938
RPS9	RPS8	P09058	893
RPS9	RPS2	P15880	880
RPS9	RPS14	P06366	860
RPS9	RPS11	P04643	836
RPS9	RPS6	P08227	814
RPS9	RPS18	P25232	809
RPS9	RPS19	P39019	802
RPS9	RPL6	Q02878	784

IntAct

348 interactions, top by confidence:

A	B	Type	Score
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
N	HNRNPR	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
LRIF1	SMCHD1	psi-mi:“MI:0914”(association)	0.680
MRPS30	GTPBP10	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPS9	RPS2	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
RPS9	STAT3	psi-mi:“MI:0915”(physical association)	0.510
STAT3	RPS9	psi-mi:“MI:0915”(physical association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
ESR1		psi-mi:“MI:0914”(association)	0.460
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410

BioGRID (852): RPS9 (Affinity Capture-MS), RPS9 (Affinity Capture-MS), RPS9 (Affinity Capture-MS), RPS9 (Affinity Capture-MS), RPS9 (Affinity Capture-MS), RNPS1 (Co-fractionation), RPL10A (Co-fractionation), RPL12 (Co-fractionation), RPL13A (Co-fractionation), RPL14 (Co-fractionation), RPL15 (Co-fractionation), RPL17 (Co-fractionation), RPL23A (Co-fractionation), RPL27A (Co-fractionation), RPL32 (Co-fractionation)

ESM2 similar proteins: A0A1D8PGY8, A0B9L2, A0RY02, A1RT03, A2SSV9, A3CWH7, A3MUS9, A4YIN4, A5UN53, A6QLG5, A7IAH7, A8MDS5, A9A436, A9L913, B1Y9B8, B4PEU8, B7NZS8, B8GEG7, C3MJP5, C3MZ03, C3N052, C3N8R6, C3NMQ2, C4KJ91, O13516, O15612, O26142, O59675, P05755, P14132, P17959, P29314, P46781, P52810, P55935, P95987, Q09757, Q20228, Q25555, Q2FT97

Diamond homologs: A0A1D8PGY8, A0B9L2, A0RY02, A0T0H2, A1RT03, A1RWT8, A2BK77, A2SSV9, A3CWH7, A3DMQ4, A3MUS9, A4FWL4, A4WM27, A4XLQ3, A4YIN4, A5UN53, A6KYH1, A6QLG5, A6UPW5, A6UW05, A6VGQ7, A7IAH7, A8A8W3, A8MDS5, A9A436, A9A9Z3, A9L913, B0R4Y0, B1L795, B1Y9B8, B2RLW6, B4PEU8, B6YSQ1, B7NZS8, B8GEG7, C0ZHK9, C3MJP5, C3MZ03, C3N052, C3N8R6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS9	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 206 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
Eukaryotic Translation Initiation	8	17.4×	5e-07
Cap-dependent Translation Initiation	8	17.4×	5e-07
SARS-CoV-1 modulates host translation machinery	8	17.4×	5e-07
Eukaryotic Translation Elongation	8	15.7×	1e-06
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	8	15.3×	1e-06
Formation of the ternary complex, and subsequently, the 43S complex	10	15.2×	4e-08
SRP-dependent cotranslational protein targeting to membrane	19	13.4×	1e-13
Peptide chain elongation	15	13.4×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	19	19.6×	1e-16
positive regulation of transcription by RNA polymerase I	5	18.0×	1e-03
mRNA stabilization	6	12.2×	1e-03
translational initiation	6	11.9×	1e-03
ribosomal small subunit biogenesis	9	11.4×	3e-05
rRNA processing	14	11.0×	1e-08
mitophagy	6	10.6×	2e-03
translation	16	9.1×	1e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2808 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54200877:T:TA	donor_gain	1.0000
19:54200878:G:GA	donor_gain	1.0000
19:54201277:GATCG:G	donor_gain	1.0000
19:54201282:G:A	donor_loss	1.0000
19:54201282:G:GG	donor_gain	1.0000
19:54201283:T:G	donor_loss	1.0000
19:54201481:CACCA:C	acceptor_loss	1.0000
19:54201482:A:AG	acceptor_gain	1.0000
19:54201485:A:AG	acceptor_gain	1.0000
19:54201485:AG:A	acceptor_gain	1.0000
19:54201486:G:GC	acceptor_gain	1.0000
19:54201486:GG:G	acceptor_gain	1.0000
19:54201486:GGC:G	acceptor_gain	1.0000
19:54201486:GGCGA:G	acceptor_gain	1.0000
19:54201606:GAAG:G	donor_gain	1.0000
19:54201607:AAG:A	donor_gain	1.0000
19:54201608:AG:A	donor_gain	1.0000
19:54201609:GG:G	donor_gain	1.0000
19:54201610:G:GA	donor_loss	1.0000
19:54201610:G:GG	donor_gain	1.0000
19:54206274:A:AG	acceptor_gain	1.0000
19:54206275:G:GG	acceptor_gain	1.0000
19:54206458:ATCAG:A	donor_loss	1.0000
19:54206459:TCAG:T	donor_loss	1.0000
19:54206460:CAGG:C	donor_loss	1.0000
19:54206461:AGGT:A	donor_loss	1.0000
19:54206462:GG:G	donor_loss	1.0000
19:54206463:GTACC:G	donor_loss	1.0000
19:54206464:T:A	donor_loss	1.0000
19:54207394:CCAG:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000166465 (19:54201826 C>T), RS1000420584 (19:54203777 C>CCA,CCG,CCT), RS1000662391 (19:54208099 A>G), RS1000771943 (19:54202843 T>A), RS1001204199 (19:54202597 C>G,T), RS1001375054 (19:54206138 C>T), RS1001390596 (19:54204727 C>A), RS1001420384 (19:54205063 A>G), RS1001491105 (19:54201264 A>T), RS1002706511 (19:54200622 A>G), RS1003130744 (19:54199404 T>C), RS1003480471 (19:54202947 C>G,T), RS1003534766 (19:54205668 C>A,T), RS1004200516 (19:54207768 A>G), RS1004748538 (19:54203139 A>G)

Disease associations

OMIM: gene MIM:603631 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006575_26	Takayasu arteritis	2.000000e-08
GCST006575_50	Takayasu arteritis	4.000000e-08
GCST008362_34	Birth weight	1.000000e-11
GCST011938_5	Takayasu arteritis	1.000000e-06
GCST011939_33	Takayasu arteritis	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066893 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds).

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

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

ChEMBL bioactivities

48 potent at pChembl≥5 of 54 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.63	Kd	0.236	nM	CHEMBL5653589
9.63	ED50	0.236	nM	CHEMBL5653589
6.52	IC50	300	nM	CHEMBL4109308
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
5.16	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

47 with measured affinity, of 209 total; 27 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149317: Binding affinity to human RPS9 incubated for 45 mins by Kinobead based pull down assay	kd	0.0002	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
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
2,2-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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases activity, increases abundance, increases expression	3
bisphenol A	increases expression, affects expression	2
chloropicrin	decreases expression	2
Arsenic	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
Cadmium Chloride	increases abundance, increases expression	2
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects 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
tetrabromobisphenol A	decreases expression	1
coumarin	decreases phosphorylation	1
artenimol	affects binding	1
arsenic trichloride	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1

ChEMBL screening assays

90 unique, capped per target: 90 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.