RPSA

Summary

RPSA (ribosomal protein SA, HGNC:6502) is a protein-coding gene on chromosome 3p22.1, encoding Small ribosomal subunit protein uS2 (P08865). Required for the assembly and/or stability of the 40S ribosomal subunit. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Many of the effects of laminin are mediated through interactions with cell surface receptors. These receptors include members of the integrin family, as well as non-integrin laminin-binding proteins. This gene encodes a high-affinity, non-integrin family, laminin receptor 1. This receptor has been variously called 67 kD laminin receptor, 37 kD laminin receptor precursor (37LRP) and p40 ribosome-associated protein. The amino acid sequence of laminin receptor 1 is highly conserved through evolution, suggesting a key biological function. It has been observed that the level of the laminin receptor transcript is higher in colon carcinoma tissue and lung cancer cell line than their normal counterparts. Also, there is a correlation between the upregulation of this polypeptide in cancer cells and their invasive and metastatic phenotype. Multiple copies of this gene exist, however, most of them are pseudogenes thought to have arisen from retropositional events. Two alternatively spliced transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 3921 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial isolated congenital asplenia (Definitive, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 185 total — 6 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_002295

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6502
Approved symbol	RPSA
Name	ribosomal protein SA
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	LRP, 37LRP, p40, SA, uS2
Ensembl gene	ENSG00000168028
Ensembl biotype	protein_coding
OMIM	150370
Entrez	3921

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 29 protein_coding, 9 retained_intron, 2 nonsense_mediated_decay

ENST00000301821, ENST00000443003, ENST00000444512, ENST00000458478, ENST00000475346, ENST00000477325, ENST00000478027, ENST00000487876, ENST00000495394, ENST00000697728, ENST00000697729, ENST00000697730, ENST00000697731, ENST00000697732, ENST00000697733, ENST00000697734, ENST00000697735, ENST00000697753, ENST00000697754, ENST00000697816, ENST00000869092, ENST00000869093, ENST00000869094, ENST00000869095, ENST00000922532, ENST00000922533, ENST00000922534, ENST00000922535, ENST00000922536, ENST00000922537, ENST00000922538, ENST00000922539, ENST00000922540, ENST00000922541, ENST00000922542, ENST00000922543, ENST00000922544, ENST00000956236, ENST00000956237, ENST00000956238

RefSeq mRNA: 2 — MANE Select: NM_002295 NM_001304288, NM_002295

CCDS: CCDS2686, CCDS77723

Canonical transcript exons

ENST00000301821 — 7 exons

Exon	Start	End
ENSE00001844671	39406720	39406764
ENSE00003514571	39410754	39410999
ENSE00003528116	39407621	39407786
ENSE00003589367	39408606	39408724
ENSE00003631075	39411896	39412061
ENSE00003659762	39411649	39411777
ENSE00003971541	39412274	39412542

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 99.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 335.6739 / max 4261.7479, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36137	332.0331	1823
36138	2.3608	1091
36139	0.9349	543
202730	0.3451	152

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.95	gold quality
right uterine tube	UBERON:0001302	99.83	gold quality
cortical plate	UBERON:0005343	99.83	gold quality
embryo	UBERON:0000922	99.80	gold quality
ganglionic eminence	UBERON:0004023	99.80	gold quality
ventricular zone	UBERON:0003053	99.79	gold quality
right ovary	UBERON:0002118	99.77	gold quality
left ovary	UBERON:0002119	99.77	gold quality
islet of Langerhans	UBERON:0000006	99.76	gold quality
ovary	UBERON:0000992	99.76	gold quality
body of pancreas	UBERON:0001150	99.76	gold quality
pancreas	UBERON:0001264	99.76	gold quality
mucosa of transverse colon	UBERON:0004991	99.75	gold quality
fallopian tube	UBERON:0003889	99.74	gold quality
lymph node	UBERON:0000029	99.73	gold quality
spleen	UBERON:0002106	99.73	gold quality
esophagus mucosa	UBERON:0002469	99.73	gold quality
body of stomach	UBERON:0001161	99.72	gold quality
skin of abdomen	UBERON:0001416	99.72	gold quality
nucleus accumbens	UBERON:0001882	99.72	gold quality
body of uterus	UBERON:0009853	99.72	gold quality
zone of skin	UBERON:0000014	99.71	gold quality
endocervix	UBERON:0000458	99.71	gold quality
right lobe of thyroid gland	UBERON:0001119	99.71	gold quality
transverse colon	UBERON:0001157	99.71	gold quality
skin of leg	UBERON:0001511	99.71	gold quality
putamen	UBERON:0001874	99.71	gold quality
adenohypophysis	UBERON:0002196	99.71	gold quality
prostate gland	UBERON:0002367	99.71	gold quality
ectocervix	UBERON:0012249	99.71	gold quality

Single-cell (SCXA)

Detected in 41 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	6794.86
E-MTAB-6308	yes	3682.65
E-MTAB-10553	yes	3571.41
E-CURD-112	yes	3459.39
E-HCAD-9	yes	3358.68
E-GEOD-125970	yes	2936.79
E-CURD-122	yes	91.05
E-CURD-46	yes	63.51
E-CURD-88	yes	62.27
E-MTAB-9221	yes	56.97
E-HCAD-11	yes	53.46
E-MTAB-8410	yes	44.22
E-MTAB-6678	yes	42.62
E-HCAD-13	yes	29.00
E-MTAB-10042	yes	16.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DBP, FOXC1, GATA6, HIF1A, PAX1, RARA, TP53

miRNA regulators (miRDB)

11 targeting RPSA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-3192-3P	98.62	65.80	970
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-4726-3P	98.49	63.89	1385

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• regulation of expression by protein p53 (PMID:12386810)
• isolation and functional characterization of the gene encoding MGr1-Ag, a multidrug-resistance-associated protein identical to the 37-kDa laminin receptor precursor (37LRP). (PMID:12440778)
• Results identify two genes, the 67-kd laminin receptor (67LR) and tumor-associated trypsin inhibitor (TATI), that may be involved in the early phases of urothelial tumor development rather than with disease progression. (PMID:12875970)
• used the intracellular portion of the alpha subunit of the GM-CSF receptor to search for interacting proteins and identified the 67-kDa laminin receptor as a binding partner (PMID:14614142)
• human Doppel fails to interact with the human 37 kDa/67 kDa LRP/LR; Dpl and PrP are not related or are only marginally related with respect to their ligand binding behaviour (PMID:15158907)
• laminin receptor precursor protein interacts with doppel (PMID:15246873)
• E. coli K1 invasion occurs through the CNF1-67-kDa laminin receptor interaction (PMID:15516338)
• 34/67 laminin receptor, carries stage-specific embryonic antigen-4 epitope defined by monoclonal antibody Raft.2 (PMID:15922307)
• full length amplification of 67LR1 gene(904 bp); could be a biomarker of malignant transformation (PMID:16431845)
• Overexpression of the recombinant 37LRP indeed led to an increase in PCK3145 binding but unexpectedly not to its uptake. (PMID:16759641)
• These findings suggest that EGCG-induced inhibition of the degranulation includes the primary binding of EGCG to the cell surface 67LR and subsequent modulation of cytoskeleton. (PMID:16889749)
• LamR plays a role in transduction by three other closely related serotypes (adeno-associated virus serotype 2 (AAV2), -3, and -9) (PMID:16973587)
• The results suggest that Lamr1 is a novel protein that interacts with human circadian clock protein hPer1 and Lamr1 is not a direct efferent element of circadian clock. (PMID:17535553)
• An effective and highly specific interaction of the surface glycoprotein E domain II (DII) of the tick born encephalitis and Dengue viruses with the laminin binding protein (LBP), is shown. (PMID:18061925)
• both eEF1A and MYPT1 have roles in EGCG signaling for cancer prevention through 67LR (PMID:18079119)
• Besides acting as a receptor for laminin, in this review 67LR also acts as a receptor for viruses, such as Sindbis virus and dengue virus, is involved with internalization of the prion protein, and is a ribosomal component. (PMID:18269348)
• These results suggest that the 37/67-kDa high affinity laminin receptor or p40 plays a critical role in maintaining cell viability. (PMID:18425431)
• is a receptor for EGCG and activates the signaling pathway. (PMID:18787295)
• Report the occurrence of autoantibodies to annexin I, 14-3-3 theta and LAMR1 in prediagnostic lung cancer sera. (PMID:18794547)
• hypoxia-elicited MGr1-Ag/37LRP expression as a pathway for resistance of gastric cancer to chemotherapeutics (PMID:19123465)
• Both at the mRNA and protein level, bile duct carcinoma cells expressed a higher level of 67LR than normal epithelial cells. (PMID:19182490)
• Results suggest that the laminin receptor is a pigment epithelium-derived factor (PEDF)receptor that mediates PEDF angiogenesis inhibition. (PMID:19224861)
• results showed that the 67LR had an enhanced over-expression in high-grade astrocytomas against normal brain tissues samples, and that the migratory activity of glioma cells was reduced after the down-regulation of the 67LR gene by RNAi (PMID:19446013)
• TSAd associates with laminin binding protein and mediates T lymphocyte migration during T cell activation (PMID:19561400)
• Tthese results show that 37LRP has some of the biological activities of 67LR, even prior to the conversion event. However, the conversion affects the sites of interaction with both laminin and heparan sulfate. (PMID:19691449)
• Results suggested that the LBP receptor domain interacting with venezuelan equine encephalitis E2 and tick-borne encephalitis virus E viral proteins is located at the C-terminal fragment of the LBP molecule. (PMID:19961413)
• 67LR induces FasL expression and cytotoxicity against Fas-sensitive Jurkat T cells in human cholangiocarcinoma cells through the phosphorylation of c-Myc on Ser-62 and the subsequent activation of the FasL promoter through the ERK pathway (PMID:20101459)
• 67LR promotes the invasive and metastatic ability of the gastric cancer cells through increasing urokinase and MMP 9 expression. (PMID:20491781)
• Studies indicate that the 37-kDa/67 kDa laminin receptor is a receptor for the cellular prion protein (PrPc). (PMID:20515747)
• Here, the authors identify a laminin binding site on LamR, comprising residues Phe32, Glu35, and Arg155, which are conserved among mammalian species. (PMID:21040730)
• Data indicate that high iLR expression was strongly correlated with negativity for CD38 and ZAP-70 expression and mutated IGVH gene status. (PMID:21055809)
• 67-kDa laminin receptor expression influenced the characteristics of leukemia cells toward an aggressive phenotype and increased the number of granulocyte-macrophage colony-stimulating factor receptors (PMID:21056082)
• the SA C-terminal domain in the spatial structure of the 40S subunit (PMID:21167900)
• The ability of LAMR to regulate viability is associated with its C-terminal 75 residues. (PMID:21243100)
• Decreased LR1 expression in cytotrophoblasts and syncytiotrophoblasts of preeclamptic placentas, which may be independent of disease severity, might have a role in shallow trophoblastic invasion in preeclampsia. (PMID:21391874)
• The genotypes and allele frequencies of the RPSA polymorphisms showed no significant differences between the controls and sporadic CJD patients. (PMID:21838916)
• The 67 kD laminin receptor is a novel PED/PEA-15 interacting protein. PED/PEA-15 overexpression increases 67LR-mediated cell adhesion and migration to laminin and extracellular matrix invasion. (PMID:21895963)
• key structural determinants of the interaction of LamR with laminin-1 (PMID:22290616)
• a high plasticity of RPSA, which could be important for its multiple cellular localizations and functional interactions (PMID:22640394)
• the nature of the EGCG-67LR interaction and novel structural insights into the understanding of 67LR-mediated functions of EGCG (PMID:22666419)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpsa	ENSDARG00000019181
mus_musculus	Rpsa	ENSMUSG00000032518
drosophila_melanogaster	sta	FBGN0003517
caenorhabditis_elegans		WBGENE00004469

Paralogs (1): RPSA2 (ENSG00000288920)

Protein

Protein identifiers

Small ribosomal subunit protein uS2 — P08865 (reviewed: P08865)

Alternative names: 37 kDa laminin receptor precursor, 37/67 kDa laminin receptor, 40S ribosomal protein SA, 67 kDa laminin receptor, Colon carcinoma laminin-binding protein, Laminin receptor 1, Laminin-binding protein precursor p40, Multidrug resistance-associated protein MGr1-Ag, NEM/1CHD4

All UniProt accessions (8): A0A0C4DG17, A0A8V8TLA4, A0A8V8TMP3, A0A8V8TMX1, A0A8V8TMZ8, C9J9K3, P08865, F8WD59

UniProt curated annotations — full annotation on UniProt →

Function. Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis. Acts as a PPP1R16B-dependent substrate of PPP1CA. (Microbial infection) Acts as a receptor for the Adeno-associated viruses 2,3,8 and 9. (Microbial infection) Acts as a receptor for the Dengue virus. (Microbial infection) Acts as a receptor for the Sindbis virus. (Microbial infection) Acts as a receptor for the Venezuelan equine encephalitis virus. (Microbial infection) Acts as a receptor for the pathogenic prion protein. (Microbial infection) Acts as a receptor for bacteria.

Subunit / interactions. Monomer (37LRP) and homodimer (67LR). 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). Interacts with RPS21. Interacts with several laminins including at least LAMB1. Interacts with MDK. The mature dimeric form interacts with PPP1R16B (via its fourth ankyrin repeat). Interacts with PPP1CA only in the presence of PPP1R16B. (Microbial infection) 67LR interacts with capsid protein of Adeno-associated virus 2,3,8 and 9. (Microbial infection) 67LR interacts with envelope protein of dengue virus. (Microbial infection) 6s7LR interacts with E2 glycoprotein of Sindbis and Venezuelan equine encephalitis virus.

Subcellular location. Cell membrane. Cytoplasm. Nucleus.

Post-translational modifications. Acylated. Acylation may be a prerequisite for conversion of the monomeric 37 kDa laminin receptor precursor (37LRP) to the mature dimeric 67 kDa laminin receptor (67LR), and may provide a mechanism for membrane association. Cleaved by stromelysin-3 (ST3) at the cell surface. Cleavage by stromelysin-3 may be a mechanism to alter cell-extracellular matrix interactions.

Disease relevance. Asplenia, isolated congenital (ICAS) [MIM:271400] A rare primary immunodeficiency and life-threatening condition, often presenting with pneumococcal sepsis. Most affected individuals die of severe bacterial infections in early childhood. Isolated asplenia is distinct from asplenia associated with other complex visceral defects, notably heterotaxy syndromes such as Ivemark syndrome. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. This protein appears to have acquired a second function as a laminin receptor specifically in the vertebrate lineage. It is thought that in vertebrates 37/67 kDa laminin receptor acquired a dual function during evolution. It developed from the ribosomal protein SA, playing an essential role in the protein biosynthesis lacking any laminin binding activity, to a cell surface receptor with laminin binding activity.

Similarity. Belongs to the universal ribosomal protein uS2 family.

RefSeq proteins (2): NP_001291217, NP_002286* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001865	Ribosomal_uS2	Family
IPR005707	Ribosomal_uS2_euk_arc	Family
IPR018130	Ribosomal_uS2_CS	Conserved_site
IPR023591	Ribosomal_uS2_flav_dom_sf	Homologous_superfamily
IPR027498	Ribosomal_uS2_euk	Family
IPR027504	Ribosomal_uS2_vert	Family
IPR032281	Ribosomal_uS2_C	Domain

Pfam: PF00318, PF16122

UniProt features (63 total): strand 12, helix 11, sequence variant 9, sequence conflict 7, region of interest 5, modified residue 5, repeat 5, turn 4, site 2, initiator methionine 1, chain 1, cross-link 1

Structure

Experimental structures (PDB)

209 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
3BCH	X-RAY DIFFRACTION	2.15
7R4X	ELECTRON MICROSCOPY	2.15
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8YOP	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
8G60	ELECTRON MICROSCOPY	2.54
8IFE	ELECTRON MICROSCOPY	2.57
9P7D	ELECTRON MICROSCOPY	2.57
9QLQ	ELECTRON MICROSCOPY	2.57

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08865-F1	79.45	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 115–116 (cleavage; by st3; site 1); 133–134 (cleavage; by st3; site 2)

Post-translational modifications (6): 2, 43, 52, 89, 97, 89

Function

Pathways and Gene Ontology

Reactome pathways

51 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-9918485	Dengue Virus Attachment and Entry
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

MSigDB gene sets: 257 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, MODULE_151, GCM_NPM1, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, HSIAO_HOUSEKEEPING_GENES, GOBP_RIBOSOME_ASSEMBLY, PATIL_LIVER_CANCER, GOBP_TRANSLATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, MURAKAMI_UV_RESPONSE_1HR_UP, GNF2_FBL

GO Biological Process (7): ribosomal small subunit assembly (GO:0000028), cytoplasmic translation (GO:0002181), translation (GO:0006412), antiviral innate immune response (GO:0140374), chromatin remodeling (GO:0006338), cell adhesion (GO:0007155), symbiont entry into host cell (GO:0046718)

GO Molecular Function (8): virus receptor activity (GO:0001618), DNA binding (GO:0003677), RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), laminin receptor activity (GO:0005055), ribosome binding (GO:0043022), laminin binding (GO:0043236), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), extracellular exosome (GO:0070062), ribosome (GO:0005840), small ribosomal subunit (GO:0015935), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Translation	2
Nonsense-Mediated Decay (NMD)	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
Dengue Virus Infection	1
Ribosome-associated quality control	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nucleic acid binding	2
ribosome	2
protein-RNA complex assembly	1
ribosome assembly	1
ribosomal small subunit biogenesis	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
innate immune response	1
defense response to virus	1
chromatin organization	1
cellular process	1
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
structural molecule activity	1
laminin binding	1
cell adhesion mediator activity	1
ribonucleoprotein complex binding	1
protein binding	1
extracellular matrix binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1
extracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

5769 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPSA	PRNP	P04156	882
RPSA	PPP1R16B	Q96T49	843
RPSA	KARS1	Q15046	839
RPSA	LGALS3	P17931	821
RPSA	ADAT2	Q7Z6V5	779
RPSA	RPS2	P15880	775
RPSA	RPL18	Q07020	766
RPSA	RPS25	P25111	745
RPSA	RPS9	P46781	728
RPSA	RPLP0	P05388	725
RPSA	RPS19	P39019	714
RPSA	RPS8	P09058	705
RPSA	ELN	P15502	697
RPSA	RPL23A	P29316	695
RPSA	GNRH2	O43555	693

IntAct

278 interactions, top by confidence:

A	B	Type	Score
RPSA	KARS1	psi-mi:“MI:0915”(physical association)	0.760
KARS1	RPSA	psi-mi:“MI:0915”(physical association)	0.760
RPSA	KARS1	psi-mi:“MI:0407”(direct interaction)	0.760
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RPSA	HSPB1	psi-mi:“MI:0915”(physical association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPSA	CCDC13	psi-mi:“MI:0915”(physical association)	0.560
CRYAA	RPSA	psi-mi:“MI:0915”(physical association)	0.560
PRKN	RPSA	psi-mi:“MI:0915”(physical association)	0.560
RPSA	WFS1	psi-mi:“MI:0915”(physical association)	0.560
RPSA	GAB2	psi-mi:“MI:0915”(physical association)	0.560
RPSA	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
KCNIP3	RPSA	psi-mi:“MI:0915”(physical association)	0.560
SOD1	RPSA	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (808): RPSA (Affinity Capture-MS), RPSA (Affinity Capture-MS), RPSA (Affinity Capture-MS), RPSA (Affinity Capture-MS), RPSA (Affinity Capture-MS), RPSA (Affinity Capture-MS), RPSA (Affinity Capture-MS), RPSA (Affinity Capture-MS), LARP7 (Affinity Capture-MS), RPL26L1 (Affinity Capture-MS), RPS21 (Affinity Capture-MS), RPSAP58 (Affinity Capture-MS), RPS27A (Affinity Capture-MS), U2SURP (Affinity Capture-MS), SF3B1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5KQE6, A1CL63, A1D695, A2I3Z2, A2Q0U8, A3RLT6, A4R188, A6NA00, A6YRY8, A7F2R3, A7RKS5, A8N7C6, B0D174, B0X6V0, B0XWG9, B2B1Z3, B2VY36, B3RPX6, B5DGB6, B5FXT6, B8M6L1, B8N513, B8PAR0, C0NKW7, C0S3U2, C1G1P4, C1GUB6, G1TLT8, P08865, P14206, P26452, P38980, P38981, P38982, P38983, P50890, Q01291, Q0PXX8, Q0UR95, Q2GV75

Diamond homologs: A0A8I5KQE6, A1D695, A2I3Z2, A2Q0U8, A3LRZ0, A3RLT6, A4R188, A4RUK2, A5BUU4, A5DGG9, A6NA00, A6RMY2, A6YRY8, A6ZUM5, A7A0V3, A7RKS5, A7TEU3, A7TIJ7, A8N7C6, A8PXY6, A8Q2H5, A8XSS1, A9UPA2, B0D174, B0X6V0, B0XWG9, B2B1Z3, B2VY36, B3LI22, B3LT19, B3MRX2, B3P9J3, B3RPX6, B4GTK1, B4I9F6, B4JXG8, B4L760, B4MB32, B4NPT0, B4PY37

SIGNOR signaling

1 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 172 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
Telomere Extension By Telomerase	5	17.2×	4e-04
Eukaryotic Translation Initiation	5	11.6×	2e-03
Cap-dependent Translation Initiation	5	11.6×	2e-03
SARS-CoV-1 modulates host translation machinery	5	11.6×	2e-03
Ribosomal scanning and start codon recognition	8	11.4×	2e-05
Formation of the ternary complex, and subsequently, the 43S complex	7	11.3×	1e-04
SRP-dependent cotranslational protein targeting to membrane	15	11.3×	3e-09
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	12	10.6×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
stress granule assembly	5	19.5×	1e-03
cytoplasmic translation	13	15.6×	2e-09
regulation of translational initiation	5	15.2×	3e-03
translational initiation	6	14.0×	1e-03
negative regulation of translation	10	12.7×	4e-06
rRNA processing	8	7.4×	2e-03
translation	11	7.3×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	3
Uncertain significance	81
Likely benign	78
Benign	7

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
64671	NM_002295.6(RPSA):c.25C>T (p.Gln9Ter)	Pathogenic
64672	NM_002295.6(RPSA):c.590_594dup (p.Pro199fs)	Pathogenic
64673	NM_002295.6(RPSA):c.538C>G (p.Arg180Gly)	Pathogenic
64674	NM_002295.6(RPSA):c.538C>T (p.Arg180Trp)	Pathogenic
64676	NM_002295.6(RPSA):c.161C>A (p.Thr54Asn)	Pathogenic
64677	NM_002295.6(RPSA):c.172C>T (p.Leu58Phe)	Pathogenic
4795154	NM_002295.6(RPSA):c.659_663del (p.Lys220fs)	Likely pathogenic
4819200	NM_002295.6(RPSA):c.493A>T (p.Asn165Tyr)	Likely pathogenic
64675	NM_002295.6(RPSA):c.556C>T (p.Arg186Cys)	Likely pathogenic

SpliceAI

905 predictions. Top by Δscore:

Variant	Effect	Δscore
3:39407776:G:GT	donor_gain	1.0000
3:39407777:A:T	donor_gain	1.0000
3:39410996:CAAGG:C	donor_loss	1.0000
3:39410997:AAGG:A	donor_loss	1.0000
3:39410998:AGGTA:A	donor_loss	1.0000
3:39410999:GGTA:G	donor_loss	1.0000
3:39411001:T:A	donor_loss	1.0000
3:39411648:GGGA:G	acceptor_gain	1.0000
3:39411775:GAG:G	donor_gain	1.0000
3:39411779:T:A	donor_loss	1.0000
3:39411886:T:A	acceptor_gain	1.0000
3:39411889:A:AG	acceptor_gain	1.0000
3:39411890:A:G	acceptor_gain	1.0000
3:39411894:A:AG	acceptor_gain	1.0000
3:39411894:AGAT:A	acceptor_loss	1.0000
3:39411894:AGATT:A	acceptor_gain	1.0000
3:39411895:G:GG	acceptor_gain	1.0000
3:39411895:GA:G	acceptor_gain	1.0000
3:39411895:GAT:G	acceptor_gain	1.0000
3:39411895:GATT:G	acceptor_gain	1.0000
3:39411895:GATTG:G	acceptor_gain	1.0000
3:39412021:TGTAC:T	donor_gain	1.0000
3:39412022:GTACA:G	donor_gain	1.0000
3:39412059:CTGGT:C	donor_loss	1.0000
3:39412062:G:GG	donor_gain	1.0000
3:39412062:GTAT:G	donor_loss	1.0000
3:39412272:A:AG	acceptor_gain	1.0000
3:39412273:G:GG	acceptor_gain	1.0000
3:39406763:GG:G	donor_gain	0.9900
3:39406764:GG:G	donor_gain	0.9900

AlphaMissense

1925 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:39407714:G:C	A21P	1.000
3:39407715:C:A	A21E	1.000
3:39407729:G:C	G26R	1.000
3:39407730:G:A	G26D	1.000
3:39407730:G:T	G26V	1.000
3:39408606:G:T	G45V	1.000
3:39408635:T:A	W55R	1.000
3:39408635:T:C	W55R	1.000
3:39408645:T:C	L58P	1.000
3:39408654:C:A	A61E	1.000
3:39408657:C:A	A62D	1.000
3:39408663:C:A	A64E	1.000
3:39408693:T:A	V74D	1.000
3:39408699:T:A	V76D	1.000
3:39408702:T:A	I77K	1.000
3:39408711:G:T	R80M	1.000
3:39408719:G:C	G83R	1.000
3:39408720:G:A	G83D	1.000
3:39410755:G:C	R85T	1.000
3:39410755:G:T	R85M	1.000
3:39410756:G:C	R85S	1.000
3:39410756:G:T	R85S	1.000
3:39410758:C:A	A86D	1.000
3:39410761:T:A	V87E	1.000
3:39410764:T:A	L88Q	1.000
3:39410764:T:C	L88P	1.000
3:39410768:G:C	K89N	1.000
3:39410768:G:T	K89N	1.000
3:39410769:T:C	F90L	1.000
3:39410770:T:C	F90S	1.000

dbSNP variants (sampled 300 via entrez): RS1000855140 (3:39406923 A>G), RS1000971865 (3:39409723 T>A), RS1001148912 (3:39409257 A>T), RS1001307781 (3:39405704 C>A,T), RS1001437430 (3:39406195 G>A,T), RS1001547689 (3:39405425 C>G,T), RS1002948314 (3:39412680 C>T), RS1003057654 (3:39406776 G>T), RS1003155004 (3:39407047 TC>T), RS1003174977 (3:39408905 T>A), RS1003390192 (3:39407976 A>G), RS1004006806 (3:39412171 C>A,T), RS1004517549 (3:39406647 C>T), RS1005116474 (3:39406707 T>C), RS1005155815 (3:39407395 C>T)

Disease associations

OMIM: gene MIM:150370 | disease phenotypes: MIM:271400

GenCC curated gene-disease

Disease	Classification	Inheritance
familial isolated congenital asplenia	Definitive	Autosomal dominant

Mondo (1): familial isolated congenital asplenia (MONDO:0010066)

Orphanet (1): Familial isolated congenital asplenia (Orphanet:101351)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001746	Asplenia
HP:0001894	Thrombocytosis
HP:0003593	Infantile onset
HP:0032550	Howell-Jolly bodies

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008557_1	Dentate gyrus volume x schizophrenia interaction	5.000000e-08

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563028	Splenic Hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6119 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 24,342 (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
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL1232461	MOLIBRESIB	2	1,538

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
7.40	Kd	39.9	nM	EPIGALOCATECHIN GALLATE
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
6.28	IC50	530	nM	MOLIBRESIB
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
5.71	Kd	1958	nM	CHEMBL3752910
5.71	ED50	1958	nM	CHEMBL3752910
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

49 with measured affinity, of 248 total; 29 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
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1977962: Binding affinity to His-tagged Laminin receptor in human A549 cells assessed as dissociation constant by surface plasmon resonance assay	kd	0.0399	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1585498: Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method	ic50	0.3000	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-3-[4-(triazolo[4,5-b]pyridin-3-yl)phenyl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3800	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3900	uM
N-(3-chloro-2-pyridinyl)-4-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4100	uM
N-(3-chloro-2-pyridinyl)-4-(5-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4500	uM
N-(1-methylpyrrolo[2,3-c]pyridin-7-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.5000	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179022: Inhibition of RPSA (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.5300	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	2149318: Binding affinity to human RPSA incubated for 45 mins by Kinobead based pull down assay	kd	1.9582	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression, affects cotreatment	6
sodium arsenite	affects binding, decreases reaction, decreases expression, affects cotreatment, increases abundance (+1 more)	3
Cadmium	increases expression, decreases reaction, increases abundance, increases palmitoylation, decreases expression	3
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression, increases expression	3
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Arsenic Trioxide	decreases expression, affects binding, decreases reaction	2
Tobacco Smoke Pollution	affects expression, increases metabolic processing	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	affects binding	1
tetrabromobisphenol A	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
bufalin	increases expression	1
perfluorooctanoic acid	decreases expression	1
butylidenephthalide	decreases expression	1
cupric oxide	increases expression	1
phenanthrene	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
perfluorodecanoic acid	decreases expression	1
chloropicrin	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
3,4,5-trihydroxy-2–methoxy-8,8-dimethyl-N-(hexahydro-2-oxo-6-(cyclohexylcarbonyl)oxy-2H-azepin-3-yl)non-6-enamide	affects metabolic processing	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1

ChEMBL screening assays

103 unique, capped per target: 103 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.