RPS13

Summary

RPS13 (ribosomal protein S13, HGNC:10386) is a protein-coding gene on chromosome 11p15.1, encoding Small ribosomal subunit protein uS15 (P62277). Component of the small ribosomal subunit. It is a common-essential gene (DepMap: required in 99.8% 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 S15P family of ribosomal proteins. It is located in the cytoplasm. The protein has been shown to bind to the 5.8S rRNA in rat. The gene product of the E. coli ortholog (ribosomal protein S15) functions at early steps in ribosome assembly. This gene is co-transcribed with two U14 small nucleolar RNA genes, which are located in its third and fifth introns. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6207 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 11 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_001017

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10386
Approved symbol	RPS13
Name	ribosomal protein S13
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	S13, uS15
Ensembl gene	ENSG00000110700
Ensembl biotype	protein_coding
OMIM	180476
Entrez	6207

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 6 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000228140, ENST00000525634, ENST00000525828, ENST00000526895, ENST00000527571, ENST00000528074, ENST00000531008, ENST00000531908, ENST00000533969, ENST00000534329, ENST00000864174, ENST00000924886, ENST00000924887, ENST00000924888, ENST00000924889, ENST00000924890, ENST00000924891, ENST00000924892, ENST00000924893

RefSeq mRNA: 1 — MANE Select: NM_001017 NM_001017

CCDS: CCDS7823

Canonical transcript exons

ENST00000525634 — 6 exons

Exon	Start	End
ENSE00002152657	17077619	17077667
ENSE00003472747	17075097	17075197
ENSE00003497234	17075454	17075623
ENSE00003521366	17077168	17077246
ENSE00003536803	17077429	17077477
ENSE00003613132	17074388	17074466

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 455.2463 / max 5911.1419, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118848	454.6924	1826
118847	0.5539	312

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.89	gold quality
leukocyte	CL:0000738	99.89	gold quality
ganglionic eminence	UBERON:0004023	99.88	gold quality
cortical plate	UBERON:0005343	99.88	gold quality
lymph node	UBERON:0000029	99.84	gold quality
left ovary	UBERON:0002119	99.84	gold quality
right ovary	UBERON:0002118	99.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.82	gold quality
endocervix	UBERON:0000458	99.82	gold quality
ovary	UBERON:0000992	99.82	gold quality
gall bladder	UBERON:0002110	99.82	gold quality
granulocyte	CL:0000094	99.81	gold quality
endometrium	UBERON:0001295	99.81	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.81	gold quality
fallopian tube	UBERON:0003889	99.81	gold quality
zone of skin	UBERON:0000014	99.80	gold quality
adipose tissue	UBERON:0001013	99.80	gold quality
left uterine tube	UBERON:0001303	99.80	gold quality
skin of abdomen	UBERON:0001416	99.80	gold quality
skin of leg	UBERON:0001511	99.80	gold quality
ventricular zone	UBERON:0003053	99.80	gold quality
thoracic mammary gland	UBERON:0005200	99.80	gold quality
body of uterus	UBERON:0009853	99.80	gold quality
omental fat pad	UBERON:0010414	99.80	gold quality
ectocervix	UBERON:0012249	99.80	gold quality
islet of Langerhans	UBERON:0000006	99.79	gold quality
smooth muscle tissue	UBERON:0001135	99.79	gold quality
body of pancreas	UBERON:0001150	99.79	gold quality
vagina	UBERON:0000996	99.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.78	gold quality

Single-cell (SCXA)

Detected in 29 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	6113.61
E-CURD-88	yes	5940.36
E-CURD-122	yes	115.40
E-MTAB-9221	yes	52.73
E-HCAD-9	yes	26.09
E-MTAB-10042	yes	16.82
E-GEOD-135922	yes	12.20
E-MTAB-6678	yes	4.72
E-MTAB-8207	no	7169.19
E-CURD-95	no	6435.12
E-GEOD-134144	no	5131.39
E-MTAB-8495	no	4612.71
E-GEOD-114530	no	4313.40
E-HCAD-5	no	4220.99
E-MTAB-7381	no	969.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, NR1I2

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• S13 subunit may possess multiple functions, including a deubiquitinylating activity and distinct activities essential for cell cycle progression that require the conserved C120 residue (PMID:12861018)
• either RPS13 or RPL23 can promote MDR in gastric cancer cells by suppressing drug-induced apoptosis, and RPL23 may also promote MDR in gastric cancer cells through regulation of glutathione S-transferase-mediated drug-detoxifying system (PMID:15149863)
• Recombinant ribosomal protein S13 expressed in and isolated from E.coli was shown to be suitable for structural and functional investigations. (PMID:15680243)
• Overproduction of rpS13 in mammalian cells interferes with splicing of its own pre-mRNA by a feedback mechanism. (PMID:17881366)
• these data indicate that RPS13 could promote the growth and cell cycle progression of gastric cancer cells at least through inhibiting p27(kip1) expression. (PMID:19912438)
• binding of ribosomal protein S13 to 18S rRNA is provided mainly by conserved motifs of the protein corresponding to those motifs in its eubacterial homologue that are involved in the interaction with 16S rRNA in the 30S subunit. (PMID:22295575)
• RPS13, a potential universal reference gene for normalisation of gene expression in multiple human normal and cancer tissue samples. (PMID:34657252)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps13	ENSDARG00000036298
mus_musculus	Rps13	ENSMUSG00000090862
rattus_norvegicus		ENSRNOG00000090662
drosophila_melanogaster	RpS13	FBGN0010265
caenorhabditis_elegans		WBGENE00004482

Protein

Protein identifiers

Small ribosomal subunit protein uS15 — P62277 (reviewed: P62277)

Alternative names: 40S ribosomal protein S13

All UniProt accessions (3): P62277, E9PS50, J3KMX5

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.

Post-translational modifications. Ubiquitinated at Lys-27 by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling).

Similarity. Belongs to the universal ribosomal protein uS15 family.

RefSeq proteins (1): NP_001008* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000589	Ribosomal_uS15	Family
IPR009068	uS15_NS1_RNA-bd_sf	Homologous_superfamily
IPR012606	Ribosomal_uS15_N	Domain
IPR023029	Ribosomal_uS15_arc_euk	Family

Pfam: PF00312, PF08069

UniProt features (21 total): helix 7, modified residue 5, strand 2, turn 2, cross-link 2, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

217 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-P62277-F1	94.29	0.93

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): 27, 27, 30, 34, 38, 27, 43

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: 199 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, AAGCAAT_MIR137, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_151, GNF2_TPT1, MORF_UBE2I, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING, GOBP_TRANSLATION, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GOBP_RNA_SPLICING, GNF2_ST13, CHNG_MULTIPLE_MYELOMA_HYPERPLOID_UP

GO Biological Process (5): cytoplasmic translation (GO:0002181), translation (GO:0006412), negative regulation of RNA splicing (GO:0033119), ribosomal small subunit biogenesis (GO:0042274), RNA processing (GO:0006396)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA binding (GO:0003729), structural constituent of ribosome (GO:0003735), mRNA 5’-UTR binding (GO:0048027), small ribosomal subunit rRNA binding (GO:0070181), protein binding (GO:0005515)

GO Cellular Component (14): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), ribosome (GO:0005840), focal adhesion (GO:0005925), postsynaptic density (GO:0014069), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), small-subunit processome (GO:0032040), extracellular exosome (GO:0070062), 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	2
nuclear lumen	2
intracellular membraneless organelle	2
translation	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
RNA splicing	1
negative regulation of gene expression	1
regulation of RNA splicing	1
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
nucleic acid binding	1
RNA binding	1
structural molecule activity	1
mRNA binding	1
rRNA binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
asymmetric synapse	1
postsynaptic specialization	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

332 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
DCC	NTN1	psi-mi:“MI:0914”(association)	0.700
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
MAGEB10	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
PRR11	NVL	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
PRPF38A	H2BC17	psi-mi:“MI:0914”(association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460

BioGRID (756): RPS13 (Affinity Capture-MS), RPS13 (Affinity Capture-MS), RPS13 (Affinity Capture-MS), RPS13 (Affinity Capture-MS), RPS13 (Affinity Capture-MS), RPS13 (Affinity Capture-MS), RPS13 (Affinity Capture-MS), RPS13 (Affinity Capture-MS), RPS13 (Affinity Capture-MS), RPS13 (Affinity Capture-MS), BRIX1 (Co-fractionation), DIMT1 (Co-fractionation), EEF1A1 (Co-fractionation), EIF2A (Co-fractionation), EIF3I (Co-fractionation)

ESM2 similar proteins: A0A1D8PPE0, A0RTT1, A2SQ60, A3CSL3, A4G0Z3, A4YIY3, A6UQM4, A6UUL9, A6VHG7, A7IAI8, A9A4V0, G1SP51, O77303, P05756, P27072, P28189, P33192, P46298, P47772, P49393, P51404, P52811, P59223, P59224, P62277, P62278, P62299, P62300, P62301, P62302, P78571, Q03334, Q05761, Q0W938, Q2FS30, Q4JAI3, Q54PH8, Q56JX8, Q69UI1, Q69UI2

Diamond homologs: A0A1D8PPE0, A0B5E6, A0RTT1, A1RSM4, A1RXJ1, A2BJY6, A2SQ60, A3CSL3, A3DMT2, A3MVD1, A4G0Z3, A4WMA2, A4YIY3, A5UMH1, A6UQM4, A6UUL9, A6VHG7, A7IAI8, A8AAU0, A8MCD3, A9A4V0, G1SP51, O27474, O29457, O57805, O77303, P05756, P05762, P27072, P28189, P33192, P46298, P47772, P49393, P51404, P52811, P54012, P59223, P59224, P62277

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS13	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 207 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
SARS-CoV-1 modulates host translation machinery	9	19.2×	2e-08
Formation of the ternary complex, and subsequently, the 43S complex	12	17.8×	2e-10
Eukaryotic Translation Initiation	8	17.0×	5e-07
Cap-dependent Translation Initiation	8	17.0×	5e-07
Nonsense-Mediated Decay (NMD)	10	16.1×	2e-08
Translation initiation complex formation	12	15.8×	5e-10
Ribosomal scanning and start codon recognition	12	15.8×	5e-10
TRAF6 mediated NF-kB activation	5	15.8×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	17	17.3×	1e-13
stress granule assembly	5	16.5×	1e-03
translational initiation	8	15.8×	9e-06
mRNA stabilization	7	14.1×	1e-04
ribosomal small subunit biogenesis	11	13.8×	2e-07
mitophagy	7	12.2×	3e-04
ribosomal large subunit biogenesis	5	12.2×	5e-03
stem cell population maintenance	5	11.6×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

563 predictions. Top by Δscore:

Variant	Effect	Δscore
11:17074463:TTCA:T	acceptor_gain	1.0000
11:17074464:TCA:T	acceptor_gain	1.0000
11:17074465:CA:C	acceptor_gain	1.0000
11:17074465:CAC:C	acceptor_gain	1.0000
11:17074467:C:CC	acceptor_gain	1.0000
11:17075091:ACTT:A	donor_loss	1.0000
11:17075092:CTT:C	donor_loss	1.0000
11:17075093:TTACT:T	donor_loss	1.0000
11:17075094:TACT:T	donor_loss	1.0000
11:17075095:A:AC	donor_gain	1.0000
11:17075095:A:C	donor_loss	1.0000
11:17075096:C:CC	donor_gain	1.0000
11:17075096:CT:C	donor_gain	1.0000
11:17075096:CTA:C	donor_gain	1.0000
11:17075096:CTAT:C	donor_gain	1.0000
11:17075096:CTATT:C	donor_gain	1.0000
11:17075448:GCTTA:G	donor_loss	1.0000
11:17075449:CTTAC:C	donor_loss	1.0000
11:17075450:TTACC:T	donor_loss	1.0000
11:17075452:A:AC	donor_gain	1.0000
11:17075453:C:CA	donor_loss	1.0000
11:17075453:C:CC	donor_gain	1.0000
11:17075453:CCTTT:C	donor_gain	1.0000
11:17075621:CAC:C	acceptor_gain	1.0000
11:17075625:T:A	acceptor_loss	1.0000
11:17077163:CTCA:C	donor_loss	1.0000
11:17077164:TCAC:T	donor_loss	1.0000
11:17077165:CA:C	donor_loss	1.0000
11:17077166:A:AC	donor_gain	1.0000
11:17077167:C:CC	donor_gain	1.0000

AlphaMissense

954 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:17074452:G:T	A146D	1.000
11:17075098:A:G	Y141H	1.000
11:17075104:A:G	W139R	1.000
11:17075104:A:T	W139R	1.000
11:17075149:G:T	R124S	1.000
11:17075169:A:G	L117P	1.000
11:17075175:A:G	L115P	1.000
11:17075180:G:C	F113L	1.000
11:17075180:G:T	F113L	1.000
11:17075182:A:G	F113L	1.000
11:17075470:A:G	L102P	1.000
11:17075551:A:G	L75P	1.000
11:17075551:A:T	L75H	1.000
11:17075608:T:A	D56V	1.000
11:17075608:T:G	D56A	1.000
11:17075609:C:G	D56H	1.000
11:17075610:T:A	R55S	1.000
11:17075610:T:G	R55S	1.000
11:17075611:C:A	R55I	1.000
11:17075611:C:G	R55T	1.000
11:17075614:A:G	L54P	1.000
11:17075623:C:T	G51D	1.000
11:17077168:C:G	G51R	1.000
11:17077246:A:G	W25R	1.000
11:17077246:A:T	W25R	1.000
11:17074440:A:T	V150D	0.999
11:17074443:A:G	L149P	0.999
11:17075102:C:A	W139C	0.999
11:17075102:C:G	W139C	0.999
11:17075103:C:G	W139S	0.999

dbSNP variants (sampled 300 via entrez): RS1000196432 (11:17076445 A>G,T), RS1000251438 (11:17076726 G>A,C,T), RS1000740367 (11:17078102 TG>T), RS1001198648 (11:17074916 T>C), RS1001651117 (11:17075176 G>A,T), RS1001760272 (11:17078753 C>T), RS1003372679 (11:17073967 C>A,G,T), RS1003388595 (11:17078241 T>A), RS1004154774 (11:17074041 A>C,G), RS1004161345 (11:17074560 T>C), RS1005833101 (11:17076007 T>C,G), RS1006388472 (11:17077509 G>A), RS1007260235 (11:17076852 C>A), RS1007436000 (11:17076393 C>A), RS1007796235 (11:17076137 C>T)

Disease associations

OMIM: gene MIM:180476 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005951_67	Body mass index	6.000000e-09
GCST005951_68	Body mass index	3.000000e-09
GCST007327_50	Smoking status (ever vs never smokers)	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004318	smoking behavior

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066850 (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

50 potent at pChembl≥5 of 54 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.18	Kd	6.565	nM	CHEMBL5653589
8.18	ED50	6.565	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
5.66	Kd	2208	nM	CHEMBL3752910
5.66	ED50	2208	nM	CHEMBL3752910
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

48 with measured affinity, of 215 total; 28 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	2149285: Binding affinity to human RPS13 incubated for 45 mins by Kinobead based pull down assay	kd	0.0066	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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149285: Binding affinity to human RPS13 incubated for 45 mins by Kinobead based pull down assay	kd	2.2081	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression, decreases expression	6
sodium arsenite	increases abundance, decreases expression, increases activity	2
Arsenic	affects cotreatment, decreases expression, increases abundance	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Rotenone	decreases expression, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Particulate Matter	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
4-oxoretinoic acid	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctanoic acid	decreases expression	1
artenimol	affects binding	1
epigallocatechin gallate	increases expression	1
arsenic trichloride	affects cotreatment, decreases expression, increases abundance	1
azoxystrobin	increases expression	1
chloropicrin	affects expression	1
deguelin	increases expression	1
fenpyroximate	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
pyrimidifen	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases 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.