RPS3A

Summary

RPS3A (ribosomal protein S3A, HGNC:10421) is a protein-coding gene on chromosome 4q31.3, encoding Small ribosomal subunit protein eS1 (P61247). 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 S3AE family of ribosomal proteins. It is located in the cytoplasm. Disruption of the gene encoding rat ribosomal protein S3a, also named v-fos transformation effector protein, in v-fos-transformed rat cells results in reversion of the transformed phenotype. This gene is co-transcribed with the U73A and U73B small nucleolar RNA genes, which are located in its fourth and third introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 6189 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 26 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10421
Approved symbol	RPS3A
Name	ribosomal protein S3A
Location	4q31.3
Locus type	gene with protein product
Status	Approved
Aliases	S3A, eS1
Ensembl gene	ENSG00000145425
Ensembl biotype	protein_coding
OMIM	180478
Entrez	6189

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 18 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000274065, ENST00000503002, ENST00000505243, ENST00000506126, ENST00000507327, ENST00000507485, ENST00000508783, ENST00000509736, ENST00000510993, ENST00000512690, ENST00000512797, ENST00000514682, ENST00000515792, ENST00000515818, ENST00000913221, ENST00000913222, ENST00000913223, ENST00000913224, ENST00000913225, ENST00000968783

RefSeq mRNA: 2 — MANE Select: NM_001006 NM_001006, NM_001267699

CCDS: CCDS3775

Canonical transcript exons

ENST00000274065 — 6 exons

Exon	Start	End
ENSE00000970488	151104472	151104642
ENSE00001152783	151100975	151101162
ENSE00002084447	151099628	151099714
ENSE00003566613	151100485	151100588
ENSE00003618397	151104177	151104286
ENSE00003674452	151102871	151103079

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.5287 / max 1278.5244, expressed in 1813 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50003	69.0359	1813
50004	4.1088	1566
50002	1.3701	644
50001	0.0139	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.96	gold quality
cortical plate	UBERON:0005343	99.96	gold quality
left ovary	UBERON:0002119	99.95	gold quality
ventricular zone	UBERON:0003053	99.95	gold quality
calcaneal tendon	UBERON:0003701	99.95	gold quality
endocervix	UBERON:0000458	99.94	gold quality
ovary	UBERON:0000992	99.94	gold quality
lymph node	UBERON:0000029	99.93	gold quality
right ovary	UBERON:0002118	99.93	gold quality
body of uterus	UBERON:0009853	99.93	gold quality
ectocervix	UBERON:0012249	99.93	gold quality
endometrium	UBERON:0001295	99.92	gold quality
fallopian tube	UBERON:0003889	99.92	gold quality
vagina	UBERON:0000996	99.91	gold quality
left uterine tube	UBERON:0001303	99.91	gold quality
uterine cervix	UBERON:0000002	99.90	gold quality
myometrium	UBERON:0001296	99.90	gold quality
right uterine tube	UBERON:0001302	99.90	gold quality
right lung	UBERON:0002167	99.90	gold quality
thoracic mammary gland	UBERON:0005200	99.90	gold quality
granulocyte	CL:0000094	99.89	gold quality
islet of Langerhans	UBERON:0000006	99.89	gold quality
pituitary gland	UBERON:0000007	99.89	gold quality
right lobe of thyroid gland	UBERON:0001119	99.89	gold quality
left lobe of thyroid gland	UBERON:0001120	99.89	gold quality
mucosa of stomach	UBERON:0001199	99.89	gold quality
skin of abdomen	UBERON:0001416	99.89	gold quality
thyroid gland	UBERON:0002046	99.89	gold quality
omental fat pad	UBERON:0010414	99.89	gold quality
monocyte	CL:0000576	99.88	gold quality

Single-cell (SCXA)

Detected in 45 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	16630.83
E-MTAB-9221	yes	8067.98
E-CURD-122	yes	6429.38
E-MTAB-6678	yes	5851.91
E-CURD-88	yes	71.50
E-HCAD-11	yes	55.96
E-MTAB-9067	yes	34.15
E-HCAD-9	yes	29.21
E-CURD-112	yes	27.09
E-MTAB-10042	yes	16.42
E-MTAB-9543	yes	12.07
E-HCAD-35	yes	7.18
E-MTAB-9801	yes	6.51
E-GEOD-137537	yes	5.75
E-HCAD-4	no	11894.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GABPA, GABPB2, SP1, TAL1

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 6)

• regulation of ribosomal S3a gene expression during cyclic amp induced neuroendocrine differentiation of LNCaP cells (PMID:12463423)
• RPS3A expression in patients with squamous cell lung cancer increased by 70% which makes it a highly informative marker of squamous cell lung cancer (PMID:15889794)
• Variants in the RPS3A homologue are associated with late-onset Alzheimer disease and implicate this gene, adjacent genes, or other functional variants (e.g., noncoding RNAs) in the pathogenesis of this disorder. (PMID:16385451)
• Results suggest that RPS3a, via extra-ribosomal chaperoning function for HBx, contributes to virally induced oncogenesis by enhancing HBx-induced NF-kappaB signaling pathway. (PMID:21857917)
• Ribosomal protein eS1 is engaged in cellular events related to processing and functioning of U11 snRNA. (PMID:28666385)
• RPS3a as an essential component for LPS-mediated pro-inflammatory signaling (PMID:29169044)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps3a	ENSDARG00000035692
drosophila_melanogaster	RpS3A	FBGN0017545
caenorhabditis_elegans		WBGENE00004470

Protein

Protein identifiers

Small ribosomal subunit protein eS1 — P61247 (reviewed: P61247)

Alternative names: 40S ribosomal protein S3a, v-fos transformation effector protein

All UniProt accessions (12): P61247, D6R9B6, D6RAS7, D6RAT0, D6RB09, D6RED7, D6RG13, D6RGE0, D6RI02, E9PFI5, H0Y8L7, H0Y9Y4

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. May play a role during erythropoiesis through regulation of transcription factor DDIT3.

Subunit / interactions. Component of the small ribosomal subunit. Mature ribosomes consist of a small (40S) and a large (60S) subunit. The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (28S, 5.8S and 5S). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Binds with high affinity to IPO4. Interacts with DDIT3. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Post-translational modifications. ADP-ribosylated at Tyr-155 by PARP1 in presence of HPF1.

Similarity. Belongs to the eukaryotic ribosomal protein eS1 family.

RefSeq proteins (2): NP_000997, NP_001254628 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001593	Ribosomal_eS1	Family
IPR018281	Ribosomal_eS1_CS	Conserved_site
IPR027500	Ribosomal_eS1_euk	Family

Pfam: PF01015

UniProt features (38 total): strand 13, modified residue 8, helix 8, cross-link 2, turn 2, initiator methionine 1, chain 1, mutagenesis site 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

216 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-P61247-F1	84.03	0.65

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 (10): 256, 263, 34, 249, 34, 56, 155, 236, 237, 249

Mutagenesis-validated functional residues (1):

Position	Phenotype
155	decreased adp-ribosylation.

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: 252 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, MODULE_151, GNF2_TPT1, GCM_NPM1, MORF_UBE2I, HSIAO_HOUSEKEEPING_GENES, DARWICHE_SKIN_TUMOR_PROMOTER_UP, GOBP_TRANSLATIONAL_INITIATION, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOBP_TRANSLATION, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME

GO Biological Process (6): cytoplasmic translation (GO:0002181), translation (GO:0006412), translational initiation (GO:0006413), cell differentiation (GO:0030154), ribosomal small subunit biogenesis (GO:0042274), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (4): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), mRNA 5’-UTR binding (GO:0048027), protein binding (GO:0005515)

GO Cellular Component (14): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), focal adhesion (GO:0005925), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), small-subunit processome (GO:0032040), synapse (GO:0045202), extracellular exosome (GO:0070062), ribonucleoprotein complex (GO:1990904), 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	3
translation	2
ribosome	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
intracellular membraneless organelle	2
cytoplasm	2
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
formation of translation initiation ternary complex	1
metabolic process	1
cellular developmental process	1
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
nucleic acid binding	1
structural molecule activity	1
mRNA binding	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
cell junction	1
extracellular vesicle	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

373 interactions, top by confidence:

A	B	Type	Score
STAU1	RPLP0	psi-mi:“MI:0914”(association)	0.750
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RPS3A	RPS14	psi-mi:“MI:0915”(physical association)	0.670
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
HSP90AA1	RPS3A	psi-mi:“MI:0915”(physical association)	0.630
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPS3A	RPL10A	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
PRR11	NVL	psi-mi:“MI:0914”(association)	0.530
KNOP1	DHX15	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
ZBTB48	ZBTB24	psi-mi:“MI:0914”(association)	0.530
E4F1	ZBTB24	psi-mi:“MI:0914”(association)	0.530

BioGRID (1096): RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS), RPS3A (Biochemical Activity), RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS), RPS3A (Affinity Capture-MS)

ESM2 similar proteins: A0RY01, A5JSW9, A7L6A0, A8E604, A8HS48, B0KW94, B3N1G9, B3P9W1, B4H9N7, B4IL76, B4JZQ9, B4L7F0, B4MEW8, B4NHI4, B5DGL6, B5FZS9, G1SS70, O43999, O44248, O73813, P05752, P52813, P55830, P55875, P61247, P97351, Q0W1V6, Q1HRR3, Q285L8, Q29CU2, Q42262, Q4T8S6, Q56FG9, Q56JV9, Q5DAA3, Q5G5C4, Q642T2, Q64FN2, Q6C169, Q6EV04

Diamond homologs: A1C4N6, A1CZL7, A2Q0R8, A2R9S1, A3LUW5, A3LX67, A4SAD2, A5B4K1, A5DN58, A5DVF8, A6R9C3, A6RZS5, A6ZM02, A7A1W1, A7E4H3, A7Q5X9, A7S3J7, A7TNP9, A8HS48, A8NX92, A8QD49, B0CY45, B0Y356, B2B5P2, B2VUE4, B3LLJ2, B3RHV0, B3S6Y0, B5FZS9, B5VNY0, B5VP69, B6HFE0, B6JWF7, B6QGS2, B8MBY6, B8NSD4, B8PIG4, B9W790, C0P0F6, C0SH35

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS3A	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 215 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SARS-CoV-1 modulates host translation machinery	8	18.4×	4e-07
TRAF6 mediated NF-kB activation	5	17.0×	2e-04
Eukaryotic Translation Initiation	7	16.1×	8e-06
Cap-dependent Translation Initiation	7	16.1×	8e-06
Nonsense-Mediated Decay (NMD)	9	15.7×	2e-07
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	17	14.9×	8e-13
Eukaryotic Translation Elongation	7	14.6×	2e-05
Peptide chain elongation	15	14.2×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	18	17.9×	8e-15
mRNA stabilization	6	11.8×	2e-03
stem cell population maintenance	5	11.3×	5e-03
positive regulation of type I interferon production	5	11.3×	5e-03
ribosomal small subunit biogenesis	9	11.0×	4e-05
intrinsic apoptotic signaling pathway	5	9.6×	9e-03
translation	17	9.4×	2e-09
rRNA processing	11	8.4×	4e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — PCM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

620 predictions. Top by Δscore:

Variant	Effect	Δscore
4:151099710:AAAGT:A	donor_gain	1.0000
4:151099711:AAGT:A	donor_gain	1.0000
4:151099713:GT:G	donor_gain	1.0000
4:151099713:GTGTA:G	donor_loss	1.0000
4:151099714:TG:T	donor_loss	1.0000
4:151099715:G:GG	donor_gain	1.0000
4:151099716:T:G	donor_loss	1.0000
4:151100483:AG:A	acceptor_gain	1.0000
4:151100484:GG:G	acceptor_gain	1.0000
4:151100484:GGGTT:G	acceptor_gain	1.0000
4:151100584:AACCA:A	donor_gain	1.0000
4:151100586:CCA:C	donor_gain	1.0000
4:151100587:CA:C	donor_gain	1.0000
4:151100587:CAG:C	donor_loss	1.0000
4:151100588:AGT:A	donor_loss	1.0000
4:151100589:G:GG	donor_gain	1.0000
4:151100590:TAA:T	donor_loss	1.0000
4:151100971:GTAG:G	acceptor_loss	1.0000
4:151100972:TAG:T	acceptor_loss	1.0000
4:151100973:A:AG	acceptor_gain	1.0000
4:151100973:AGAA:A	acceptor_loss	1.0000
4:151100974:G:GT	acceptor_gain	1.0000
4:151100974:GA:G	acceptor_gain	1.0000
4:151100974:GAA:G	acceptor_gain	1.0000
4:151100974:GAAA:G	acceptor_gain	1.0000
4:151100974:GAAAT:G	acceptor_gain	1.0000
4:151101162:GGTGA:G	donor_loss	1.0000
4:151101163:G:GC	donor_loss	1.0000
4:151101164:T:A	donor_loss	1.0000
4:151102867:CCA:C	acceptor_loss	1.0000

AlphaMissense

1767 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:151099662:G:C	G4R	1.000
4:151100504:A:G	K28E	1.000
4:151100505:A:T	K28I	1.000
4:151100506:A:C	K28N	1.000
4:151100506:A:T	K28N	1.000
4:151100510:T:A	W30R	1.000
4:151100510:T:C	W30R	1.000
4:151100511:G:C	W30S	1.000
4:151100512:G:C	W30C	1.000
4:151100512:G:T	W30C	1.000
4:151100513:T:G	Y31D	1.000
4:151100520:T:A	V33E	1.000
4:151100526:C:A	A35E	1.000
4:151100529:C:A	P36H	1.000
4:151100537:T:A	F39I	1.000
4:151100537:T:C	F39L	1.000
4:151100538:T:C	F39S	1.000
4:151100539:C:A	F39L	1.000
4:151100539:C:G	F39L	1.000
4:151100555:G:A	G45R	1.000
4:151100555:G:C	G45R	1.000
4:151100556:G:A	G45E	1.000
4:151100556:G:T	G45V	1.000
4:151100568:T:A	V49D	1.000
4:151100574:G:C	R51T	1.000
4:151100574:G:T	R51M	1.000
4:151100575:G:C	R51S	1.000
4:151100575:G:T	R51S	1.000
4:151100577:C:T	T52I	1.000
4:151100582:G:A	G54R	1.000

dbSNP variants (sampled 300 via entrez): RS1000025259 (4:151097643 T>C), RS1000120214 (4:151103814 A>G), RS1000223231 (4:151097869 A>G), RS1000407038 (4:151104037 T>G), RS1000873413 (4:151104163 T>G), RS1001006030 (4:151102551 T>C), RS1001359684 (4:151103269 A>C), RS1001541648 (4:151102241 C>G,T), RS1001681655 (4:151104836 CTCAT>C), RS1002062663 (4:151103765 TAC>T,TACAC,TACACAC), RS1002593085 (4:151101805 T>G), RS1003354283 (4:151100110 C>G,T), RS1003596744 (4:151100299 C>T), RS1003985913 (4:151104202 A>C,G,T), RS1004008509 (4:151098717 G>A)

Disease associations

OMIM: gene MIM:180478 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000755_26	HDL cholesterol	7.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067564 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

49 potent at pChembl≥5 of 53 total, top 48 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
5.61	Kd	2452	nM	CHEMBL3752910
5.61	ED50	2452	nM	CHEMBL3752910
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
5.46	IC50	3440	nM	MOLIBRESIB
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 213 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
N-(3-methyl-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.0500	uM
N-(3-chloro-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	2.0800	uM
N-(5,8-dihydroisoquinolin-1-yl)-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1584424: Inhibition of human 80S ribosome-mediated PCSK9 translation expressed in CHO-K1 cells assessed as reduction in PCSK9 secretion	ec50	2.2000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149306: Binding affinity to human RPS3A incubated for 45 mins by Kinobead based pull down assay	kd	2.4525	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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178766: Inhibition of RPS3A (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	3.4400	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
sodium arsenite	affects reaction, increases expression, increases methylation, decreases expression, increases activity	3
epigallocatechin gallate	decreases expression, increases expression, affects cotreatment	2
Caffeine	decreases phosphorylation, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	affects sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction, increases reaction	1
sodium bichromate	increases expression	1
nickel subsulfide	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
chromium hexavalent ion	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	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
fenbuconazole	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression, increases reaction	1
LDN 193189	affects cotreatment, decreases expression	1

ChEMBL screening assays

96 unique, capped per target: 96 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1920845	Binding	Induction of ribosome to readthrough in human A-T lymphoblastoid cells assessed as ATM ser1981 autophosphorylation at 30 uM after 4 days by PTT-ELISA assay	Synthesis and evaluation of compounds that induce readthrough of premature termination codons. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.