RPS12

Summary

RPS12 (ribosomal protein S12, HGNC:10385) is a protein-coding gene on chromosome 6q23.2, encoding Small ribosomal subunit protein eS12 (P25398). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic 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 S12E family of ribosomal proteins. It is located in the cytoplasm. Increased expression of this gene in colorectal cancers compared to matched normal colonic mucosa has been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6206 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 21 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_001016

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10385
Approved symbol	RPS12
Name	ribosomal protein S12
Location	6q23.2
Locus type	gene with protein product
Status	Approved
Aliases	S12, eS12
Ensembl gene	ENSG00000112306
Ensembl biotype	protein_coding
OMIM	603660
Entrez	6206

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 18 protein_coding, 1 retained_intron

ENST00000230050, ENST00000484616, ENST00000877750, ENST00000877751, ENST00000877752, ENST00000914101, ENST00000914102, ENST00000914103, ENST00000914104, ENST00000914105, ENST00000914106, ENST00000914107, ENST00000914108, ENST00000914109, ENST00000914110, ENST00000914111, ENST00000914112, ENST00000914113, ENST00000914114

RefSeq mRNA: 1 — MANE Select: NM_001016 NM_001016

CCDS: CCDS5164

Canonical transcript exons

ENST00000230050 — 6 exons

Exon	Start	End
ENSE00001332599	132814569	132814613
ENSE00001379351	132814972	132815088
ENSE00003470289	132814732	132814782
ENSE00003482174	132816960	132817061
ENSE00003557159	132816461	132816563
ENSE00003569530	132817480	132817564

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1199.4884 / max 18681.0589, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69829	1199.4884	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	99.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.95	gold quality
ovary	UBERON:0000992	99.95	gold quality
right ovary	UBERON:0002118	99.95	gold quality
zone of skin	UBERON:0000014	99.94	gold quality
lymph node	UBERON:0000029	99.94	gold quality
endocervix	UBERON:0000458	99.94	gold quality
skin of abdomen	UBERON:0001416	99.94	gold quality
skin of leg	UBERON:0001511	99.94	gold quality
ectocervix	UBERON:0012249	99.94	gold quality
granulocyte	CL:0000094	99.93	gold quality
vagina	UBERON:0000996	99.93	gold quality
right uterine tube	UBERON:0001302	99.93	gold quality
body of uterus	UBERON:0009853	99.93	gold quality
omental fat pad	UBERON:0010414	99.93	gold quality
metanephros cortex	UBERON:0010533	99.93	gold quality
breast	UBERON:0000310	99.92	gold quality
adipose tissue	UBERON:0001013	99.92	gold quality
right lobe of thyroid gland	UBERON:0001119	99.92	gold quality
left lobe of thyroid gland	UBERON:0001120	99.92	gold quality
mucosa of stomach	UBERON:0001199	99.92	gold quality
left uterine tube	UBERON:0001303	99.92	gold quality
spleen	UBERON:0002106	99.92	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.92	gold quality
fallopian tube	UBERON:0003889	99.92	gold quality
thoracic mammary gland	UBERON:0005200	99.92	gold quality
upper lobe of left lung	UBERON:0008952	99.92	gold quality
esophagus	UBERON:0001043	99.91	gold quality
saliva-secreting gland	UBERON:0001044	99.91	gold quality
myometrium	UBERON:0001296	99.91	gold quality

Single-cell (SCXA)

Detected in 57 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	16321.01
E-MTAB-10042	yes	15219.92
E-CURD-122	yes	12320.26
E-MTAB-9221	yes	12054.64
E-CURD-88	yes	10798.32
E-CURD-112	yes	9656.58
E-HCAD-31	yes	4433.18
E-GEOD-137537	yes	3624.12
E-MTAB-6678	yes	2385.43
E-MTAB-9067	yes	28.49
E-HCAD-35	yes	7.28
E-MTAB-9801	yes	6.38
E-CURD-120	no	17217.14
E-CURD-55	no	17011.33
E-HCAD-15	no	14215.32

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, ZBED1, ZBTB4

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 6)

• may be early molecular diagnostic marker for cervical squamous cell carcinoma (PMID:11870519)
• Our findings provide the first demonstration that RPS12 plays important roles in regulating the proliferation and migration of gastric cancer cells. S100A4 can mediate the effects of RPS12 as a downstream effector (PMID:23546393)
• Streptomycin resistance is mainly related to mutation at codons 43 and 88 “rpsL” gene and to a lesser extent “rrs” that are the greatest cause of drug resistance to streptomycin. (PMID:26963306)
• Our data suggest that RPS12 (eS12) is enriched in hypoxic monosomes, which increases the heavy polysome association of structured transcripts APAF-1 and XIAP. Furthermore, hypoxia induced five alternative splicing events within a subset of RP mRNAs in cell lines (PMID:31911497)
• Molecular analysis of streptomycin-resistance associating genes in Mycobacterium tuberculosis isolates from Nepal. (PMID:32829153)
• HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis. (PMID:33273532)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps12	ENSDARG00000036875
rattus_norvegicus		ENSRNOG00000087613
rattus_norvegicus	Rps12l2	ENSRNOG00000088532
drosophila_melanogaster	RpS12	FBGN0286213
caenorhabditis_elegans		WBGENE00004481

Protein

Protein identifiers

Small ribosomal subunit protein eS12 — P25398 (reviewed: P25398)

Alternative names: 40S ribosomal protein S12

All UniProt accessions (1): P25398

UniProt curated annotations — full annotation on UniProt →

Function. 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 of the 40S ribosomal complex.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Subunit of the 40S ribosomal complex.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Similarity. Belongs to the eukaryotic ribosomal protein eS12 family.

RefSeq proteins (1): NP_001007* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000530	Ribosomal_eS12	Family
IPR004038	Ribosomal_eL8/eL30/eS12/Gad45	Domain
IPR029064	Ribosomal_eL30-like_sf	Homologous_superfamily
IPR047860	Ribosomal_eS12_CS	Conserved_site

Pfam: PF01248

UniProt features (23 total): strand 9, helix 6, sequence conflict 3, modified residue 2, initiator methionine 1, chain 1, turn 1

Structure

Experimental structures (PDB)

198 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
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
9S3C	ELECTRON MICROSCOPY	2.42
9QLO	ELECTRON MICROSCOPY	2.47
9P8B	ELECTRON MICROSCOPY	2.48
7XNY	ELECTRON MICROSCOPY	2.5
8G60	ELECTRON MICROSCOPY	2.54
8IFE	ELECTRON MICROSCOPY	2.57
9P7D	ELECTRON MICROSCOPY	2.57
9QLQ	ELECTRON MICROSCOPY	2.57
8IFD	ELECTRON MICROSCOPY	2.59
9P7E	ELECTRON MICROSCOPY	2.59
6ZLW	ELECTRON MICROSCOPY	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25398-F1	80.99	0.05

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): 2, 129

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: 230 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, GNF2_TPT1, MORF_UBE2I, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_TRANSLATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, MORF_CCNI, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, LUI_TARGETS_OF_PAX8_PPARG_FUSION, GNF2_FBL, BYSTROEM_CORRELATED_WITH_IL5_UP

GO Biological Process (5): cytoplasmic translation (GO:0002181), translation (GO:0006412), ribosomal small subunit biogenesis (GO:0042274), positive regulation of canonical Wnt signaling pathway (GO:0090263), maintenance of translational fidelity (GO:1990145)

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

GO Cellular Component (12): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), small-subunit processome (GO:0032040), 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
translation	2
macromolecule biosynthetic process	2
ribosome	2
nuclear lumen	2
cytoplasm	2
intracellular membrane-bounded organelle	2
intracellular membraneless organelle	2
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
protein metabolic process	1
protein biosynthetic process	1
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
nucleic acid binding	1
structural molecule activity	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
protein-containing complex	1

Protein interactions and networks

STRING

3936 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS12	RPLP0	P05388	698
RPS12	GFM1	Q96RP9	632
RPS12	RPL18	Q07020	631
RPS12	RPS25	P25111	620
RPS12	EIF5B	O60841	619
RPS12	RPSA	P08865	599
RPS12	ECEL1	O95672	548
RPS12	MRPS12	O15235	536
RPS12	MTIF2	P46199	508
RPS12	EED	O75530	490
RPS12	RPL30	P04645	457
RPS12	RPS17	P08708	455
RPS12	RPL7A	P11518	435
RPS12	RPS26	P02383	430
RPS12	RPS18	P25232	422
RPS12	RPS10	P46783	422

IntAct

181 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPS12	RPS10	psi-mi:“MI:0915”(physical association)	0.560
RPS12	HTT	psi-mi:“MI:0915”(physical association)	0.560
RPS6	IPO7	psi-mi:“MI:0914”(association)	0.530
RPS11	RPS17	psi-mi:“MI:0403”(colocalization)	0.530
HMGB1	RPS12	psi-mi:“MI:0915”(physical association)	0.480
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
ZNF124	RPS12	psi-mi:“MI:0915”(physical association)	0.400
GCH1	RPS12	psi-mi:“MI:0915”(physical association)	0.400
BCL7A	RPS12	psi-mi:“MI:0915”(physical association)	0.400
ACTB	DDX3X	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Cbx1		psi-mi:“MI:0914”(association)	0.350

BioGRID (510): RPS12 (Affinity Capture-MS), RPS12 (Affinity Capture-MS), FAU (Co-fractionation), RPL10 (Co-fractionation), RPL10A (Co-fractionation), RPL11 (Co-fractionation), RPL12 (Co-fractionation), RPL13 (Co-fractionation), RPL13A (Co-fractionation), RPL14 (Co-fractionation), RPL15 (Co-fractionation), RPL21 (Co-fractionation), RPL22 (Co-fractionation), RPL23 (Co-fractionation), RPL24 (Co-fractionation)

ESM2 similar proteins: A0JPD7, A4FUZ6, B4F6I3, B5X9L9, C1C416, D5JWB3, G1SFR8, O13019, O17433, O43099, O82491, P25398, P46405, P47840, P52570, P63324, P84175, P99029, Q28IJ3, Q2PF16, Q39227, Q3ZBK2, Q42663, Q43754, Q43772, Q504A5, Q5F204, Q5HZX7, Q5ZI34, Q641F0, Q6AXX6, Q6AZG8, Q6DK91, Q6GLW8, Q6GM16, Q6GM65, Q6NV24, Q6PBP3, Q6QHK0, Q76I81

Diamond homologs: A4YIL9, B8D6E8, C5A1V9, G1SFR8, O13019, O14062, O59936, O74322, O97249, P25398, P46405, P47840, P48589, P49196, P63323, P63324, P80455, P84175, Q03253, Q4J8P1, Q54PX9, Q5ADQ6, Q5JGR3, Q76I81, Q97EH1, Q9S9P1, Q9SKZ3, Q9SMI3, Q9XHS0, A8A912, B6YWH9, C3MJN1, C3MYY9, C3N038, C3N8Q2, C3NMR6, C4KJ77, P54066, P55858, P62008

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ZBED1	“up-regulates quantity by expression”	RPS12	“transcriptional regulation”
RPS12	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 181 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	7	17.1×	5e-06
Cap-dependent Translation Initiation	7	17.1×	5e-06
SARS-CoV-1 modulates host translation machinery	7	17.1×	5e-06
Formation of the ternary complex, and subsequently, the 43S complex	10	17.1×	1e-08
Eukaryotic Translation Elongation	7	15.5×	9e-06
Eukaryotic Translation Termination	16	15.3×	7e-13
SRP-dependent cotranslational protein targeting to membrane	19	15.1×	1e-14
Formation of a pool of free 40S subunits	17	15.1×	1e-13

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	18	21.8×	2e-16
stress granule assembly	5	19.7×	8e-04
translational initiation	7	16.4×	5e-05
negative regulation of translation	9	11.5×	3e-05
translation	16	10.8×	1e-09
ribosomal small subunit biogenesis	6	8.9×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

866 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:132815057:G:A	G34R	1.000
6:132815057:G:C	G34R	1.000
6:132815058:G:A	G34E	1.000
6:132815073:C:A	A39D	1.000
6:132816478:G:A	C50Y	1.000
6:132816479:T:G	C50W	1.000
6:132816481:T:A	V51E	1.000
6:132816535:G:A	C69Y	1.000
6:132816536:T:G	C69W	1.000
6:132816981:G:A	G86R	1.000
6:132816981:G:C	G86R	1.000
6:132816982:G:A	G86E	1.000
6:132816982:G:T	G86V	1.000
6:132817042:G:A	C106Y	1.000
6:132817043:C:G	C106W	1.000
6:132817047:T:C	C108R	1.000
6:132817048:G:A	C108Y	1.000
6:132817049:T:G	C108W	1.000
6:132817054:T:A	V110E	1.000
6:132817057:T:A	V111D	1.000
6:132815007:C:A	A17D	0.999
6:132815022:T:A	L22Q	0.999
6:132815022:T:C	L22P	0.999
6:132815030:G:C	A25P	0.999
6:132815031:C:A	A25D	0.999
6:132815034:T:C	L26P	0.999
6:132815049:T:C	L31P	0.999
6:132815058:G:T	G34V	0.999
6:132815069:G:C	A38P	0.999
6:132815070:C:A	A38D	0.999

dbSNP variants (sampled 300 via entrez): RS1000421697 (6:132814751 C>T), RS1000519286 (6:132814207 T>G), RS1001612348 (6:132813329 T>C), RS1002374186 (6:132815044 T>G), RS1002516999 (6:132814168 C>G,T), RS1002633164 (6:132813883 T>G), RS1003704262 (6:132817514 T>C), RS1004153349 (6:132815116 G>A), RS1004662688 (6:132816307 T>C), RS1005713289 (6:132815542 C>G,T), RS1005715320 (6:132816953 C>A,T), RS1006203552 (6:132814545 T>A,C), RS1006665168 (6:132814619 T>C), RS1006669276 (6:132814577 C>T), RS1007261028 (6:132818042 T>C)

Disease associations

OMIM: gene MIM:603660 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000909_2	Type 2 diabetes nephropathy	2.000000e-06
GCST006979_392	Heel bone mineral density	2.000000e-13
GCST007989_9	Facial morphology traits (63 three-dimensional facial segments)	6.000000e-12
GCST009325_42	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1.000000e-10
GCST010796_2602	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_2603	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_2604	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST010796_2605	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_2606	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066936 (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
6.77	Kd	171.1	nM	CHEMBL3752910
6.77	ED50	171.1	nM	CHEMBL3752910
6.59	Kd	254.4	nM	CHEMBL5653589
6.59	ED50	254.4	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

48 with measured affinity, of 209 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149284: Binding affinity to human RPS12 incubated for 45 mins by Kinobead based pull down assay	kd	0.1711	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149284: Binding affinity to human RPS12 incubated for 45 mins by Kinobead based pull down assay	kd	0.2544	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
bisphenol A	affects expression, decreases expression, increases expression, increases methylation	7
Particulate Matter	decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression, affects binding (+1 more)	2
Arsenic	increases expression, decreases expression, increases abundance, affects cotreatment	2
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
alpha phellandrene	decreases expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
tetrabromobisphenol A	increases expression	1
phenanthrene	decreases expression	1
myricetin	decreases expression	1
arsenic trichloride	decreases expression, increases abundance, affects cotreatment	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
pterostilbene	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	increases methylation	1
LDN 193189	affects cotreatment, decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
bisphenol AF	increases expression	1
Artesunate	decreases response to substance	1
Benztropine	affects cotreatment, decreases 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.