RPS8

Summary

RPS8 (ribosomal protein S8, HGNC:10441) is a protein-coding gene on chromosome 1p34.1, encoding Small ribosomal subunit protein eS8 (P62241). Component of the small ribosomal subunit. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S8E family of ribosomal proteins. It is located in the cytoplasm. Increased expression of this gene in colorectal tumors and colon polyps compared to matched normal colonic mucosa has been observed. This gene is co-transcribed with the small nucleolar RNA genes U38A, U38B, U39, and U40, which are located in its fourth, fifth, first, and second introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6202 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 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_001012

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10441
Approved symbol	RPS8
Name	ribosomal protein S8
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	S8, eS8
Ensembl gene	ENSG00000142937
Ensembl biotype	protein_coding
OMIM	600357
Entrez	6202

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000372209, ENST00000396651, ENST00000464658, ENST00000470475, ENST00000474582, ENST00000484599, ENST00000485390, ENST00000497035, ENST00000932905, ENST00000932906, ENST00000932907, ENST00000932908, ENST00000932909

RefSeq mRNA: 1 — MANE Select: NM_001012 NM_001012

CCDS: CCDS513

Canonical transcript exons

ENST00000396651 — 6 exons

Exon	Start	End
ENSE00001887000	44775540	44775600
ENSE00003548419	44776034	44776140
ENSE00003593120	44778000	44778129
ENSE00003597943	44778576	44778779
ENSE00003633713	44776675	44776774
ENSE00003673164	44777614	44777789

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.6945 / max 360.7132, expressed in 1820 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2639	37.8800	1819
2642	1.7584	856
2638	0.4757	276
2640	0.3232	112
201495	0.1411	46
201494	0.1161	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	99.94	gold quality
ovary	UBERON:0000992	99.93	gold quality
right ovary	UBERON:0002118	99.93	gold quality
endocervix	UBERON:0000458	99.90	gold quality
body of uterus	UBERON:0009853	99.90	gold quality
uterine cervix	UBERON:0000002	99.89	gold quality
right adrenal gland	UBERON:0001233	99.89	gold quality
left adrenal gland	UBERON:0001234	99.89	gold quality
right uterine tube	UBERON:0001302	99.89	gold quality
fallopian tube	UBERON:0003889	99.89	gold quality
ganglionic eminence	UBERON:0004023	99.89	gold quality
cortical plate	UBERON:0005343	99.89	gold quality
left adrenal gland cortex	UBERON:0035825	99.89	gold quality
lymph node	UBERON:0000029	99.88	gold quality
left uterine tube	UBERON:0001303	99.88	gold quality
ectocervix	UBERON:0012249	99.88	gold quality
right adrenal gland cortex	UBERON:0035827	99.88	gold quality
vagina	UBERON:0000996	99.87	gold quality
myometrium	UBERON:0001296	99.87	gold quality
skin of abdomen	UBERON:0001416	99.87	gold quality
prostate gland	UBERON:0002367	99.87	gold quality
adrenal gland	UBERON:0002369	99.87	gold quality
ventricular zone	UBERON:0003053	99.87	gold quality
thoracic mammary gland	UBERON:0005200	99.87	gold quality
zone of skin	UBERON:0000014	99.86	gold quality
stromal cell of endometrium	CL:0002255	99.85	gold quality
adipose tissue	UBERON:0001013	99.85	gold quality
skin of leg	UBERON:0001511	99.85	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.85	gold quality
omental fat pad	UBERON:0010414	99.85	gold quality

Single-cell (SCXA)

Detected in 45 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	10523.56
E-CURD-122	yes	7885.60
E-MTAB-9221	yes	53.97
E-HCAD-11	yes	51.69
E-CURD-112	yes	39.29
E-MTAB-6678	yes	35.56
E-HCAD-9	yes	19.28
E-MTAB-9543	yes	18.70
E-MTAB-10042	yes	17.14
E-MTAB-7316	yes	15.41
E-MTAB-8498	yes	12.07
E-HCAD-35	yes	9.72
E-MTAB-9801	yes	6.31
E-GEOD-137537	yes	5.87
E-HCAD-23	no	12407.44

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 2)

• RPS8, a member of the small subunit ribosome, was identified as an interacting partner of CDK11p46. (PMID:21371428)
• Identification of 40S ribosomal protein S8 as a novel biomarker for alcoholassociated hepatocellular carcinoma using weighted gene coexpression network analysis. (PMID:32627011)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps8a	ENSDARG00000055996
danio_rerio	rps8b	ENSDARG00000057368
mus_musculus	Rps8	ENSMUSG00000047675
rattus_norvegicus	Rps8	ENSRNOG00000054626
drosophila_melanogaster	RpS8	FBGN0039713
caenorhabditis_elegans		WBGENE00004477

Protein

Protein identifiers

Small ribosomal subunit protein eS8 — P62241 (reviewed: P62241)

Alternative names: 40S ribosomal protein S8

All UniProt accessions (3): P62241, Q5JR94, Q5JR95

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Component of the small ribosomal subunit. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.

Subcellular location. Cytoplasm. Membrane. Nucleus. Nucleolus.

Similarity. Belongs to the eukaryotic ribosomal protein eS8 family.

RefSeq proteins (1): NP_001003* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001047	Ribosomal_eS8	Family
IPR018283	Ribosomal_eS8_CS	Conserved_site
IPR022309	Ribosomal_Se8/biogenesis_NSA2	Family
IPR042563	Ribosomal_protein_eS8_euk	Homologous_superfamily

Pfam: PF01201

UniProt features (34 total): strand 12, helix 10, modified residue 4, cross-link 2, initiator methionine 1, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

214 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-P62241-F1	93.02	0.83

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): 193, 37, 128, 130, 160, 2, 170

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: 262 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, GCM_NPM1, GOBP_MATURATION_OF_SSU_RRNA, HSIAO_HOUSEKEEPING_GENES, YY1_Q6, GGCNKCCATNK_UNKNOWN, GOBP_TRANSLATION, GCM_PSME1, MARTINEZ_RB1_TARGETS_DN, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, chr1p34, GNF2_FBL

GO Biological Process (4): maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462), cytoplasmic translation (GO:0002181), translation (GO:0006412), ribosomal small subunit biogenesis (GO:0042274)

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

GO Cellular Component (14): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), focal adhesion (GO:0005925), 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), nucleolus (GO:0005730), ribosome (GO:0005840)

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
intracellular membrane-bounded organelle	2
nuclear lumen	2
cytoplasm	2
intracellular membraneless organelle	2
maturation of SSU-rRNA	1
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
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
nucleic acid binding	1
structural molecule activity	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
cell-substrate junction	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
extracellular vesicle	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

379 interactions, top by confidence:

A	B	Type	Score
STAU1	RPLP0	psi-mi:“MI:0914”(association)	0.750
N	HNRNPR	psi-mi:“MI:0914”(association)	0.730
NCAPH2	SMC2	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
INAVA	CYTH3	psi-mi:“MI:0914”(association)	0.640
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPS11	RPS8	psi-mi:“MI:0915”(physical association)	0.560
RPS8	DLG2	psi-mi:“MI:0915”(physical association)	0.560
RPS8	DLG3	psi-mi:“MI:0915”(physical association)	0.560
NOM1	RPLP0	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL8	RRP8	psi-mi:“MI:0914”(association)	0.530
E4F1	ZBTB24	psi-mi:“MI:0914”(association)	0.530
MRPL28	MRPL3	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
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (1109): RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS), RPS8 (Affinity Capture-MS)

ESM2 similar proteins: A0L5X7, A0LIJ4, A1T0D8, A1USL8, A5CUA9, A6QCQ2, A7NR59, A7SMR0, A9BHA1, A9KD27, A9KJJ0, A9NAM8, A9WH70, B0RB43, B1GZ87, B1VAE4, B2S2E0, B3EGY6, B6J259, B6J5D6, B8FET1, B9LJD6, C4KZP2, C6C189, G1TJW1, O83223, P04596, P56026, P56366, P62241, P62242, P62243, P62660, P80381, Q0ANQ4, Q0BYB8, Q19VA9, Q1K8V2, Q1KVT8, Q30Z46

Diamond homologs: A0B8P7, A1CJS8, A1RS21, A2BK08, A2STM4, A3CSQ2, A3DNX9, A3MWY2, A4G0R4, A4WLM9, A4YD47, A5UNB3, A6UQT9, A6UWP2, A6VHS1, A7IAR0, A8AAJ7, A9A907, B0R639, B1Y9T9, B6YTF2, B8GJR4, B9LQC4, C3MJ42, C3MYT4, C3MZT9, C3N864, C3NF48, C4KJ22, C5A4I6, G1TJW1, O14049, O26309, O28130, O58830, O76756, O81361, P0CX39, P0CX40, P25204

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS8	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 219 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
Formation of the ternary complex, and subsequently, the 43S complex	9	12.2×	2e-06
Translation initiation complex formation	10	12.0×	4e-07
Ribosomal scanning and start codon recognition	10	12.0×	4e-07
SARS-CoV-1 modulates host translation machinery	6	11.7×	3e-04
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	15	11.1×	1e-09
L13a-mediated translational silencing of Ceruloplasmin expression	17	10.8×	1e-10
GTP hydrolysis and joining of the 60S ribosomal subunit	17	10.7×	1e-10
Formation of a pool of free 40S subunits	15	10.6×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	5	28.8×	7e-05
mRNA stabilization	9	16.9×	7e-07
stress granule assembly	5	15.4×	1e-03
translational initiation	8	14.7×	1e-05
cytoplasmic translation	15	14.2×	8e-11
mitophagy	8	13.0×	3e-05
stem cell population maintenance	6	13.0×	5e-04
translation	21	11.1×	4e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

967 predictions. Top by Δscore:

Variant	Effect	Δscore
1:44775933:C:G	donor_gain	1.0000
1:44776029:T:G	acceptor_gain	1.0000
1:44776033:GGC:G	acceptor_gain	1.0000
1:44776104:G:GT	donor_gain	1.0000
1:44776771:GAGT:G	donor_gain	1.0000
1:44776773:GT:G	donor_gain	1.0000
1:44776775:G:GG	donor_gain	1.0000
1:44776779:G:GG	donor_gain	1.0000
1:44777609:AGCAG:A	acceptor_loss	1.0000
1:44777610:GCA:G	acceptor_loss	1.0000
1:44777611:CAGGT:C	acceptor_loss	1.0000
1:44777612:A:C	acceptor_loss	1.0000
1:44777613:G:T	acceptor_loss	1.0000
1:44777735:GTG:G	donor_gain	1.0000
1:44777778:G:GT	donor_gain	1.0000
1:44777786:GCTG:G	donor_gain	1.0000
1:44777995:TTCA:T	acceptor_loss	1.0000
1:44777996:TCA:T	acceptor_loss	1.0000
1:44777998:A:AG	acceptor_gain	1.0000
1:44777998:A:AT	acceptor_loss	1.0000
1:44777999:G:GA	acceptor_gain	1.0000
1:44777999:GA:G	acceptor_gain	1.0000
1:44777999:GACT:G	acceptor_gain	1.0000
1:44777999:GACTC:G	acceptor_gain	1.0000
1:44776027:C:G	acceptor_gain	0.9900
1:44776028:A:AG	acceptor_gain	0.9900
1:44776028:AT:A	acceptor_gain	0.9900
1:44776029:TGCA:T	acceptor_loss	0.9900
1:44776030:GCAGG:G	acceptor_loss	0.9900
1:44776031:CA:C	acceptor_loss	0.9900

AlphaMissense

1345 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:44776059:G:C	K10N	1.000
1:44776059:G:T	K10N	1.000
1:44776072:G:T	G15W	1.000
1:44776073:G:A	G15E	1.000
1:44776117:G:A	G30R	1.000
1:44776117:G:C	G30R	1.000
1:44776117:G:T	G30W	1.000
1:44776118:G:A	G30E	1.000
1:44776130:C:A	A34D	1.000
1:44776700:T:A	V46D	1.000
1:44776711:G:A	G50R	1.000
1:44776711:G:C	G50R	1.000
1:44776712:G:A	G50E	1.000
1:44776712:G:T	G50V	1.000
1:44776729:C:A	R56S	1.000
1:44776733:C:A	A57D	1.000
1:44776736:T:C	L58P	1.000
1:44776739:G:T	R59M	1.000
1:44776750:G:A	G63R	1.000
1:44776750:G:C	G63R	1.000
1:44776750:G:T	G63W	1.000
1:44776751:G:A	G63E	1.000
1:44776755:T:A	N64K	1.000
1:44776755:T:G	N64K	1.000
1:44776762:T:A	W67R	1.000
1:44776762:T:C	W67R	1.000
1:44777632:G:T	R77M	1.000
1:44777654:T:A	N84K	1.000
1:44777654:T:G	N84K	1.000
1:44777667:G:A	E89K	1.000

dbSNP variants (sampled 300 via entrez): RS1000374451 (1:44777152 G>C), RS1001053651 (1:44773624 A>G), RS1001572494 (1:44778458 A>G), RS1002100619 (1:44776212 C>A), RS1002496332 (1:44774649 C>G), RS1002854316 (1:44774475 C>T), RS1003081053 (1:44775795 G>A,C,T), RS1004247964 (1:44776238 G>C), RS1005072649 (1:44778820 A>G), RS1005196463 (1:44774739 T>C), RS1005747743 (1:44774935 T>A), RS1006185349 (1:44777509 T>G), RS1006631955 (1:44775391 G>A), RS1006745067 (1:44775091 G>A,C), RS1008082192 (1:44776910 T>G)

Disease associations

OMIM: gene MIM:600357 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067571 (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
6.52	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
5.79	Kd	1621	nM	CHEMBL3752910
5.79	ED50	1621	nM	CHEMBL3752910
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
5.02	Kd	9510	nM	CHEMBL5653589
5.02	ED50	9510	nM	CHEMBL5653589

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
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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149316: Binding affinity to human RPS8 incubated for 45 mins by Kinobead based pull down assay	kd	1.6211	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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149316: Binding affinity to human RPS8 incubated for 45 mins by Kinobead based pull down assay	kd	9.5098	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, affects cotreatment	3
sodium arsenite	increases activity, affects binding, increases reaction, decreases expression	3
chloropicrin	decreases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
deoxynivalenol	increases expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	affects binding, increases reaction	1
artenimol	affects binding	1
perfluorooctane sulfonic acid	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
ICG 001	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Amphotericin B	increases expression	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects localization, increases expression, affects cotreatment	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Ozone	affects expression, increases abundance	1
Ribonucleotides	affects binding	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.