RPS4Y1

Summary

RPS4Y1 (ribosomal protein S4 Y-linked 1, HGNC:10425) is a protein-coding gene on chromosome Yp11.2, encoding Small ribosomal subunit protein eS4, Y isoform 1 (P22090).

Cytoplasmic ribosomes, 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 ribosomal protein S4, a component of the 40S subunit. Ribosomal protein S4 is the only ribosomal protein known to be encoded by more than one gene, namely this gene and ribosomal protein S4, X-linked (RPS4X). The 2 isoforms encoded by these genes are not identical, but are functionally equivalent. Ribosomal protein S4 belongs to the S4E family of ribosomal proteins. It has been suggested that haploinsufficiency of the ribosomal protein S4 genes plays a role in Turner syndrome; however, this hypothesis is controversial. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6192 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 38 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001008

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10425
Approved symbol	RPS4Y1
Name	ribosomal protein S4 Y-linked 1
Location	Yp11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC5070, MGC119100, S4
Ensembl gene	ENSG00000129824
Ensembl biotype	protein_coding
OMIM	470000
Entrez	6192

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000250784, ENST00000430575, ENST00000477725, ENST00000515575

RefSeq mRNA: 1 — MANE Select: NM_001008 NM_001008

CCDS: CCDS14773

Canonical transcript exons

ENST00000250784 — 7 exons

Exon	Start	End
ENSE00001601989	2854600	2854771
ENSE00001602849	2845646	2845743
ENSE00001709586	2842165	2842242
ENSE00001738202	2844077	2844257
ENSE00002490412	2841602	2841627
ENSE00003636667	2866793	2867268
ENSE00003667463	2865088	2865245

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 70.0738 / max 1525.7708, expressed in 918 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201091	69.7662	918
201092	0.3075	156

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.53	gold quality
prostate gland	UBERON:0002367	99.28	gold quality
caput epididymis	UBERON:0004358	99.28	gold quality
penis	UBERON:0000989	99.22	gold quality
right lung	UBERON:0002167	99.20	gold quality
corpus epididymis	UBERON:0004359	99.19	gold quality
tendon of biceps brachii	UBERON:0008188	99.19	gold quality
metanephros cortex	UBERON:0010533	99.16	gold quality
rectum	UBERON:0001052	99.15	gold quality
epididymis	UBERON:0001301	99.14	gold quality
trabecular bone tissue	UBERON:0002483	99.06	gold quality
adult organism	UBERON:0007023	99.05	gold quality
urethra	UBERON:0000057	98.98	gold quality
cauda epididymis	UBERON:0004360	98.98	gold quality
type B pancreatic cell	CL:0000169	98.88	gold quality
synovial joint	UBERON:0002217	98.84	gold quality
mucosa of transverse colon	UBERON:0004991	98.81	gold quality
seminal vesicle	UBERON:0000998	98.78	gold quality
mucosa of urinary bladder	UBERON:0001259	98.78	gold quality
vena cava	UBERON:0004087	98.53	gold quality
apex of heart	UBERON:0002098	98.39	gold quality
tongue squamous epithelium	UBERON:0006919	98.32	gold quality
gluteal muscle	UBERON:0002000	98.26	gold quality
right testis	UBERON:0004534	98.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.03	gold quality
left testis	UBERON:0004533	98.00	gold quality
cranial nerve II	UBERON:0000941	97.99	gold quality
blood vessel layer	UBERON:0004797	97.91	gold quality
testis	UBERON:0000473	97.71	gold quality
middle frontal gyrus	UBERON:0002702	97.46	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	1224.07
E-HCAD-56	yes	1124.28
E-GEOD-149689	yes	1003.80
E-CURD-55	yes	901.80
E-MTAB-7407	yes	838.53
E-MTAB-9221	yes	645.35
E-HCAD-11	yes	581.41
E-GEOD-89232	yes	491.27
E-CURD-46	yes	28.77
E-HCAD-9	yes	26.67
E-MTAB-9067	yes	26.30
E-MTAB-6678	yes	16.25
E-MTAB-10042	yes	15.31
E-ANND-3	yes	14.01
E-GEOD-125970	yes	13.82

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• In a CD4 single-positive T cell clone (or the line from which clones were derived) RPS4Y was identified as the gene encoding an HLA-DRDR7-restricted HY epitope. (PMID:23225889)
• DLG1, XIST, DDX3Y and RPS4Y1 genes can classify samples into different group clearly, and they are regarded as high confidence distinct gene biomarkers of Parkinson disease. (PMID:25275262)
• Identification of Potential Biomarkers for Intervertebral Disc Degeneration Using the Genome-Wide Expression Analysis. (PMID:31904996)
• Identification of Ribosomal Protein S4, Y-Linked 1 as a cyclosporin A plus corticosteroid resistance gene. (PMID:32331925)
• Development of a Specific Monoclonal Antibody to Detect Male Cells Expressing the RPS4Y1 Protein. (PMID:33670450)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps4x	ENSDARG00000014690
drosophila_melanogaster	RpS4	FBGN0011284
caenorhabditis_elegans		WBGENE00004473

Paralogs (2): RPS4X (ENSG00000198034), RPS4Y2 (ENSG00000280969)

Protein

Protein identifiers

Small ribosomal subunit protein eS4, Y isoform 1 — P22090 (reviewed: P22090)

Alternative names: 40S ribosomal protein S4

All UniProt accessions (2): P22090, C9JEH7

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the eukaryotic ribosomal protein eS4 family.

RefSeq proteins (1): NP_000999* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000876	Ribosomal_eS4	Family
IPR002942	S4_RNA-bd	Domain
IPR005824	KOW	Domain
IPR013843	Ribosomal_eS4_N	Domain
IPR013845	Ribosomal_eS4_central_region	Domain
IPR014722	Rib_uL2_dom2	Homologous_superfamily
IPR018199	Ribosomal_eS4_N_CS	Conserved_site
IPR032277	Ribosomal_eS4_C	Domain
IPR036986	S4_RNA-bd_sf	Homologous_superfamily
IPR038237	Ribosomal_eS4_central_sf	Homologous_superfamily
IPR041982	Ribosomal_eS4_KOW	Domain

Pfam: PF00467, PF00900, PF08071, PF16121

UniProt features (2 total): chain 1, domain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6OLG	ELECTRON MICROSCOPY	3.4
5AJ0	ELECTRON MICROSCOPY	3.5
5FLX	ELECTRON MICROSCOPY	3.9
6OLZ	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22090-F1	95.57	0.97

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: 119 (showing top): MCLACHLAN_DENTAL_CARIES_UP, MODULE_151, GOBP_TRANSLATION, MODULE_66, LEE_NAIVE_T_LYMPHOCYTE, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, LINDVALL_IMMORTALIZED_BY_TERT_UP, MODULE_29, YAMASHITA_LIVER_CANCER_WITH_EPCAM_UP, MODULE_114, REACTOME_METABOLISM_OF_RNA, RUNNE_GENDER_EFFECT_UP, GOCC_RIBOSOME, GOCC_CYTOSOLIC_SMALL_RIBOSOMAL_SUBUNIT, GOCC_SMALL_RIBOSOMAL_SUBUNIT

GO Biological Process (1): translation (GO:0006412)

GO Molecular Function (3): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), rRNA binding (GO:0019843)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), ribosome (GO:0005840), membrane (GO:0016020), cytosolic small ribosomal subunit (GO:0022627), 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	3
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
ribosome	1
RNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
intracellular membraneless organelle	1
small ribosomal subunit	1
cytosolic ribosome	1
protein-containing complex	1

Protein interactions and networks

STRING

2152 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS4Y1	EIF1AY	O14602	846
RPS4Y1	DDX3Y	O15523	816
RPS4Y1	USP9Y	O00507	801
RPS4Y1	ZFY	P08048	786
RPS4Y1	KDM5D	Q9BY66	784
RPS4Y1	PHKA1	P46020	778
RPS4Y1	UTY	O14607	727
RPS4Y1	SLC16A2	P36021	718
RPS4Y1	TMSB4Y	O14604	706
RPS4Y1	PRKY	O43930	673
RPS4Y1	A0A087WUC5	A0A087WUC5	633
RPS4Y1	AMELY	Q99218	623
RPS4Y1	HSFY1	Q96LI6	585
RPS4Y1	NLGN4Y	Q8NFZ3	575
RPS4Y1	TXLNG	Q9NUQ3	565

IntAct

43 interactions, top by confidence:

A	B	Type	Score
ACTR3	ARPC1B	psi-mi:“MI:0914”(association)	0.890
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
ACTR3B	ARPC2	psi-mi:“MI:0914”(association)	0.670
CA5B	DBT	psi-mi:“MI:0914”(association)	0.560
ALDOA	ALDOB	psi-mi:“MI:0914”(association)	0.550
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
WDR37	CLUH	psi-mi:“MI:0914”(association)	0.530
PHYHIPL	RPS4Y1	psi-mi:“MI:0915”(physical association)	0.400
PADI4	RPS4Y1	psi-mi:“MI:0915”(physical association)	0.400
AK3	RPS4Y1	psi-mi:“MI:0915”(physical association)	0.400
UGT3A1	RPS4Y1	psi-mi:“MI:0915”(physical association)	0.400
CD55	RPS4Y1	psi-mi:“MI:0915”(physical association)	0.400
LIN28A	MEX3A	psi-mi:“MI:0914”(association)	0.350
NCAPD3	BIN1	psi-mi:“MI:0914”(association)	0.350
CZIB	ERI3	psi-mi:“MI:0914”(association)	0.350
NEU2	PEX14	psi-mi:“MI:0914”(association)	0.350
TMCC2	RPS4Y1	psi-mi:“MI:0914”(association)	0.350
RBKS	RPS4Y1	psi-mi:“MI:0914”(association)	0.350
ACOT7	RPS4Y1	psi-mi:“MI:0914”(association)	0.350
RPS4Y1	CCT3	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
RPL10A	GTPBP10	psi-mi:“MI:0914”(association)	0.350
ZC3H10	GTPBP10	psi-mi:“MI:0914”(association)	0.350
WRAP53	POTEF	psi-mi:“MI:0914”(association)	0.350
PINK1	A2ML1	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
RPS8		psi-mi:“MI:0914”(association)	0.350
RPSA2		psi-mi:“MI:0914”(association)	0.350
NEUROG3	MYO9A	psi-mi:“MI:0914”(association)	0.350
RPS19	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350

BioGRID (133): RPS4Y1 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y1 (Affinity Capture-MS), RPS4Y1 (Biochemical Activity), RPS4Y1 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y1 (Affinity Capture-MS), RPS4Y1 (Affinity Capture-MS), RPS4Y1 (Affinity Capture-MS), RPS4Y1 (Affinity Capture-MS), RPS4Y1 (Affinity Capture-MS), RPS4Y1 (Affinity Capture-MS), RPS4Y1 (Affinity Capture-MS), RPS4Y1 (Affinity Capture-MS), RPS4Y1 (Two-hybrid)

ESM2 similar proteins: A0A1D8PCI6, A4FWA9, A6VGZ7, G1TK17, O22424, O59950, O62738, O62739, P0CX35, P0CX36, P22090, P41042, P46299, P46300, P47836, P47837, P47961, P49204, P49398, P49401, P51405, P62701, P62702, P62703, P62704, P62705, P79103, P79183, P87158, Q0W1X6, Q4GXU6, Q4PMB3, Q56FH2, Q5UAP0, Q642H9, Q6GVM7, Q6PBC4, Q76MY1, Q76N24, Q861U7

Diamond homologs: A0A1D8PCI6, A1RS06, A2BMD1, A3DNB9, A3MWZ7, A4FWA9, A4WLL4, A4YCX8, A5UL76, A6UQ56, A6UWV0, A6VGZ7, A8ACD4, A8MB20, A9A9Q2, B1L778, B1Y9S4, B8D5V8, C3MQ71, C3MVJ0, C3N5T9, C3NEF5, C3NH97, C4KHG8, G1TK17, O05634, O22424, O26123, O28366, O59430, O59950, O62738, O62739, O81363, P0C233, P0CX35, P0CX36, P14023, P22090, P41042

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS4Y1	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 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
Regulation of expression of SLITs and ROBOs	5	8.7×	9e-03
Major pathway of rRNA processing in the nucleolus and cytosol	5	7.7×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	5	16.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
870524	GRCh37/hg19 Yp11.31(chrY:2650140-2777517)x1	Pathogenic

SpliceAI

1079 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:2841625:ATGGT:A	donor_loss	1.0000
Y:2841626:TGGTA:T	donor_loss	1.0000
Y:2841627:GGTAA:G	donor_loss	1.0000
Y:2841628:GTA:G	donor_loss	1.0000
Y:2841629:T:G	donor_loss	1.0000
Y:2842159:TTTCA:T	acceptor_loss	1.0000
Y:2842160:TTCAG:T	acceptor_loss	1.0000
Y:2842162:CA:C	acceptor_loss	1.0000
Y:2842163:A:AG	acceptor_gain	1.0000
Y:2842164:G:GG	acceptor_gain	1.0000
Y:2842164:GGCCC:G	acceptor_gain	1.0000
Y:2842240:TTT:T	donor_gain	1.0000
Y:2842241:TT:T	donor_gain	1.0000
Y:2842241:TTG:T	donor_loss	1.0000
Y:2842242:TGTG:T	donor_loss	1.0000
Y:2842243:G:GG	donor_gain	1.0000
Y:2842244:T:A	donor_loss	1.0000
Y:2842245:GAGTA:G	donor_loss	1.0000
Y:2842246:AGTAT:A	donor_loss	1.0000
Y:2844074:CA:C	acceptor_loss	1.0000
Y:2844075:A:AG	acceptor_gain	1.0000
Y:2844075:A:T	acceptor_loss	1.0000
Y:2844076:G:GG	acceptor_gain	1.0000
Y:2844255:TGGGT:T	donor_loss	1.0000
Y:2844256:GG:G	donor_gain	1.0000
Y:2844256:GGGTA:G	donor_loss	1.0000
Y:2844257:GG:G	donor_gain	1.0000
Y:2844257:GGTA:G	donor_loss	1.0000
Y:2844258:G:T	donor_loss	1.0000
Y:2844259:T:G	donor_loss	1.0000

AlphaMissense

1731 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:2842240:T:C	F27L	0.999
Y:2842242:T:A	F27L	0.999
Y:2842242:T:G	F27L	0.999
Y:2842213:T:A	W18R	0.998
Y:2842213:T:C	W18R	0.998
Y:2844159:C:A	A55E	0.998
Y:2844116:T:C	C41R	0.997
Y:2844118:T:G	C41W	0.997
Y:2854673:G:C	R145P	0.997
Y:2865207:T:C	F218L	0.997
Y:2865209:T:A	F218L	0.997
Y:2865209:T:G	F218L	0.997
Y:2844186:T:A	I64K	0.996
Y:2844249:G:A	G85E	0.996
Y:2845682:G:C	R100P	0.996
Y:2865124:G:A	G190D	0.996
Y:2865127:G:C	R191P	0.996
Y:2844101:C:G	H36D	0.995
Y:2854605:G:C	K122N	0.995
Y:2854605:G:T	K122N	0.995
Y:2865123:G:C	G190R	0.995
Y:2865124:G:T	G190V	0.995
Y:2842171:G:C	G4R	0.994
Y:2842191:G:C	K10N	0.994
Y:2842191:G:T	K10N	0.994
Y:2844078:C:A	A28E	0.994
Y:2844095:G:C	G34R	0.994
Y:2844096:G:A	G34D	0.994
Y:2845681:C:A	R100S	0.994
Y:2845706:G:C	R108P	0.994

dbSNP variants (sampled 300 via entrez): RS1000839858 (Y:2867594 G>A,T), RS1002030689 (Y:2855552 G>A), RS1003297610 (Y:2848527 G>T), RS1003861355 (Y:2850115 G>A), RS1004859766 (Y:2848606 A>G), RS1006086311 (Y:2840734 C>T), RS1006623166 (Y:2857484 C>G), RS1007107872 (Y:2858959 T>C), RS1007700090 (Y:2865671 G>C), RS1008041350 (Y:2863992 A>T), RS1008371132 (Y:2852787 T>C), RS1008713971 (Y:2851231 A>G), RS1009979660 (Y:2860109 A>G), RS1010030453 (Y:2859172 T>C), RS1010650842 (Y:2846330 C>T)

Disease associations

OMIM: gene MIM:470000 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX)

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

46 potent at pChembl≥5 of 50 total, top 45 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
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

46 with measured affinity, of 205 total; 26 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
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

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
arsenite	increases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Catechin	affects cotreatment, increases expression	1
Chromium	decreases expression	1
Hydralazine	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	decreases expression, increases abundance	1
Valproic Acid	affects cotreatment, decreases expression	1
Vanadates	increases expression	1

ChEMBL screening assays

89 unique, capped per target: 89 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.