RPS19

Summary

RPS19 (ribosomal protein S19, HGNC:10402) is a protein-coding gene on chromosome 19q13.2, encoding Small ribosomal subunit protein eS19 (P39019). Component of the small ribosomal subunit. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

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 S19E family of ribosomal proteins. It is located in the cytoplasm. Mutations in this gene cause Diamond-Blackfan anemia (DBA), a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors, in a subset of patients. This suggests a possible extra-ribosomal function for this gene in erythropoietic differentiation and proliferation, in addition to its ribosomal function. Higher expression levels of this gene in some primary colon carcinomas compared to matched normal colon tissues has been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6223 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Diamond-Blackfan anemia (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 298 total — 57 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 94
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001022

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10402
Approved symbol	RPS19
Name	ribosomal protein S19
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	S19, eS19, DBA
Ensembl gene	ENSG00000105372
Ensembl biotype	protein_coding
OMIM	603474
Entrez	6223

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000221975, ENST00000593863, ENST00000598261, ENST00000598399, ENST00000598466, ENST00000598742, ENST00000600467, ENST00000601492, ENST00000858696, ENST00000858697, ENST00000933915, ENST00000933916

RefSeq mRNA: 4 — MANE Select: NM_001022 NM_001022, NM_001321483, NM_001321484, NM_001321485

CCDS: CCDS12588

Canonical transcript exons

ENST00000598742 — 6 exons

Exon	Start	End
ENSE00000842533	41869699	41869753
ENSE00002997047	41860255	41860289
ENSE00003086085	41871351	41872925
ENSE00003559995	41860775	41860845
ENSE00003620290	41869031	41869214
ENSE00003628391	41861112	41861212

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 90.5540 / max 669.3673, expressed in 1822 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176074	58.2901	1817
176073	26.1453	1799
176075	3.2326	1342
176072	1.6686	896
208836	1.2175	744

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.95	gold quality
right uterine tube	UBERON:0001302	99.94	gold quality
skin of hip	UBERON:0001554	99.94	gold quality
granulocyte	CL:0000094	99.92	gold quality
lower esophagus mucosa	UBERON:0035834	99.92	gold quality
embryo	UBERON:0000922	99.91	gold quality
penis	UBERON:0000989	99.91	gold quality
skin of leg	UBERON:0001511	99.91	gold quality
gingival epithelium	UBERON:0001949	99.91	gold quality
zone of skin	UBERON:0000014	99.90	gold quality
mammalian vulva	UBERON:0000997	99.90	gold quality
skin of abdomen	UBERON:0001416	99.90	gold quality
gingiva	UBERON:0001828	99.90	gold quality
nipple	UBERON:0002030	99.90	gold quality
spleen	UBERON:0002106	99.90	gold quality
thymus	UBERON:0002370	99.89	gold quality
cartilage tissue	UBERON:0002418	99.89	gold quality
mucosa of transverse colon	UBERON:0004991	99.89	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.89	gold quality
cortical plate	UBERON:0005343	99.89	gold quality
ovary	UBERON:0000992	99.88	gold quality
superficial temporal artery	UBERON:0001614	99.88	gold quality
right ovary	UBERON:0002118	99.88	gold quality
left ovary	UBERON:0002119	99.88	gold quality
ventricular zone	UBERON:0003053	99.88	gold quality
ganglionic eminence	UBERON:0004023	99.88	gold quality
colonic mucosa	UBERON:0000317	99.87	gold quality
endocervix	UBERON:0000458	99.87	gold quality
pylorus	UBERON:0001166	99.87	gold quality
esophagus mucosa	UBERON:0002469	99.87	gold quality

Single-cell (SCXA)

Detected in 50 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	6994.45
E-MTAB-10042	yes	5599.77
E-MTAB-6678	yes	3181.87
E-GEOD-137537	yes	2850.03
E-HCAD-35	yes	2819.14
E-ENAD-17	yes	2035.10
E-GEOD-180759	yes	1897.46
E-CURD-122	yes	90.17
E-MTAB-9221	yes	52.69
E-CURD-112	yes	42.45
E-HCAD-9	yes	30.94
E-HCAD-31	yes	24.15
E-MTAB-7316	yes	17.70
E-MTAB-9543	yes	10.79
E-MTAB-9801	yes	6.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Study suggests that RPS19 overexpression might be a universal signal in rapid cell growth tissues. (PMID:11942409)
• results indicated that the conversion of the RP S19 dimer from agonist to antagonist of C5a receptor is attributed to the IAGQVAAANKK moiety between Ile134 and Lys144 (PMID:12651630)
• Histopathological grading of the HNSCC biopsies correlated significantly with the S19 mRNA expression levels. (PMID:15330156)
• RPS19 silencing decreases the proliferative capacity of hematopoietic progenitors and leads to a defect in erythroid development (PMID:15626736)
• Deficiency of RPS19 blocks proliferation of immature erythroid progenitor cells; dexamethasone activates proliferation of the same cell population through mechanisms independent of RPS19 (PMID:15755903)
• Rps19 has a role in the assembly and maturation of the pre-40 S ribosomal particles (PMID:16159874)
• The PIM-1/RPS19 interaction was demonstrated both in vitro and in living cells and led to phosphorylation of RPS19 in an in vitro kinase assay. (PMID:16266891)
• in CD34- cells from the bone marrow of patients with DBA harboring mutations in RPS19 was revealed a pre-rRNA-processing defect similar to that observed in TF-1 cells where RPS19 expression was reduced (PMID:16990592)
• ribosome biogenesis and nucleolar organization is altered in skin fibroblasts from DBA patients bearing mutations in the RPS19 gene (PMID:17053056)
• RPS19 mutations affecting RPS19 conserved arginines R56Q and R62Q could significantly inhibit the rate of protein synthesis, indicating the importance of RPS19 in translation. (PMID:17082006)
• RPS19 is a ribosomal protein linked to Diamond-Blackfan anemia (PMID:17178250)
• The RP S19 dimer inhibits C5a-induced neutrophil migration and promotes apoptosis of neutrophils via the C5a receptor. (PMID:17199736)
• Diamond-Blackfan anemia missense mutations affect the assembly of ribosomal protein S19 into the ribosome (PMID:17517689)
• RPS19 deficiency causes apoptosis and accelerated loss of erythroid progenitors in RPS19-deficient Diamond-Blackfan anemia. (PMID:17962699)
• patients with RPS19 mutations display a poorer response to steroids and a worse long-term prognosis compared to other Diamond-Blackfan anemia patients (Review) (PMID:18412286)
• Demonstration of an important role for the proteasomal degradation pathway in regulating the expression levels and nucleolar localization of certain mutant RPS19 proteins in Diamond-Blackfan anemia. (PMID:18768533)
• RPS19 significantly compromised CXCR2-dependent MIF-triggered adhesion of monocytes to endothelial cells under flow conditions. We, therefore, propose that RPS19 acts as an extracellular negative regulator of MIF. (PMID:19155217)
• siRNA knock-down of RPS19 results in a relative decrease of small subunit r-proteins (S20, S21 and S24) when compared to large subunit r-proteins (L3, L9, L30 and L38). This correlates with a relative decrease in 18S rRNA with respect to 28S rRNA. (PMID:19454283)
• Specific alleles at predicted transcription factor binding sites may alter the expression of RPS19, modify an important interaction between transcription factors with overlapping TFBS or remove an important stimulus for hematopoiesis (PMID:19587786)
• Primary fibroblasts from Diamond-Blackfan anemia patients with truncating mutations in RPS19 or in RPS24 have a marked reduction in proliferative capacity. (PMID:19689926)
• Genetic variants in the noncoding region of RPS19 gene in Diamond-Blackfan anemia: potential implications for phenotypic heterogeneity. (PMID:20054847)
• A molecule indistinguishable from RP S19 was present in plasma, and that the RP S19-like molecule was converted to the active form by a transglutaminase-catalyzed reaction. (PMID:20093496)
• Data show that all patients with RPS19 and RPL5 mutations had physical abnormalities. (PMID:20378560)
• RPS19 binds specifically to the 5’ untranslated region of its own mRNA; Diamond-Blackfan anemia missense mutations introduced into RPS19 impair this binding. (PMID:20395159)
• Data show that when a Gi/PI3K pathway is partially blocked, C5a receptors stimulate an alternative p38MAPK pathway. (PMID:20473571)
• approximately 30% of RPS19 mutations are missense mutations that do not alter the stability of the RPS19 protein and are hypothesized to act by a dominant negative mechanism in Diamond-Blackfan anemia (PMID:20606162)
• PIM1 may act as a sensor for ribosomal stress independently of or in concert with the known p53-dependent mechanisms. (PMID:20639905)
• p53 accumulates selectively in the erythroid lineage in primary human hematopoietic progenitor cells after expression of shRNAs targeting RPS14, the ribosomal protein gene deleted in the 5q-syndrome, or RPS19. (PMID:21068437)
• N-mediated translation initiation mechanism, which lures the host translation machinery for the preferential translation of viral transcripts, primarily depends on the N-RPS19 interaction. (PMID:21296889)
• translocation of RP S19 from prothrombin to platelets during blood coagulation (PMID:21306436)
• The RPS19 gene uses a broad range of transcriptional start sites and a short 5’UTR is associated with increased levels of RPS19. (PMID:21412415)
• the monocyte C5aR selectively activates the classical pathway with the binding of C5a and the alternative pathway with the binding of C5a/RP S19. (PMID:21613290)
• Studies identified deletions at known Diamond-Blackfan anemia (DBA)-related ribosomal protein gene loci in 17% (9 of 51) of patients without an identifiable mutation, including RPS19, RPS17, RPS26, and RPL35A. (PMID:22045982)
• Data show 1 proband with an RPL5 deletion, 1 patient with an RPL35A deletion, 3 with RPS17 deletions, and 1 with an RPS19 deletion. (PMID:22262766)
• Single nucleotide polymorphisms in the RPS19 and RPS19 is associated with HPV persistence and cervical precancer/cancer. (PMID:22496757)
• High frequency of RPS19 gene deletion is associated with Italian Diamond-Blackfan anemia. (PMID:22689679)
• RPS19 mutations induced a decrease in proliferation of progenitor cells, but the terminal erythroid differentiation was normal with little or no apoptosis. (PMID:22833095)
• Study of genetic risk of prevalent hrHPV infections in Nigerian women found significant associations with SNPs on ribosomal protein gene S19 (RPS19) and Thymidylate Synthase gene (TYMS), in an allelic model. This risk remained significant, after adjusting for age, body mass index, smoking, age at menarche, age at sexual debut, lifetime total number of sexual partners and the total number of pregnancies. (PMID:23826176)
• levels of branched-chain aminotransferase-1 (BCAT1) transcripts are significantly decreased on the polysomes of both RPS19 and RPL11 cells and that translation of BCAT1 protein is especially impaired in cells with small RP gene mutations (PMID:24463277)
• increase of autophagy in cells derived from DBA patients, in CD34+ erythrocyte progenitor cells with RPS19 knock down, in the red blood cells of zebrafish embryos with RP-deficiency, and in cells from patients with Shwachman-Diamond syndrome (PMID:24875531)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps19	ENSDARG00000030602
drosophila_melanogaster	RpS19b	FBGN0039129

Protein

Protein identifiers

Small ribosomal subunit protein eS19 — P39019 (reviewed: P39019)

Alternative names: 40S ribosomal protein S19

All UniProt accessions (6): A0A075B6E2, B0ZBD0, P39019, M0QYF7, M0R140, M0R2L9

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. Required for pre-rRNA processing and maturation of 40S ribosomal subunits. 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. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with RPS19BP1; the interaction is direct and mediates the integration of RPS19 in state post-A1. Interacts with RPS19BP1. (Microbial infection) Interacts with Sin nombre virus nucleoprotein (via N-terminus); this interaction probably mediates the loading of the 40S ribosomal subunit on viral capped mRNA during N-mediated translation initiation.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Tissue specificity. Higher level expression is seen in the colon carcinoma tissue than normal colon tissue.

Disease relevance. Diamond-Blackfan anemia 1 (DBA1) [MIM:105650] An autosomal dominant form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of developing leukemia. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the eukaryotic ribosomal protein eS19 family.

RefSeq proteins (4): NP_001013, NP_001308412, NP_001308413, NP_001308414 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001266	Ribosomal_eS19	Family
IPR018277	Ribosomal_eS19_CS	Conserved_site
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF01090

UniProt features (48 total): sequence variant 27, strand 7, helix 6, modified residue 5, initiator methionine 1, chain 1, turn 1

Structure

Experimental structures (PDB)

210 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-P39019-F1	92.01	0.89

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 (5): 23, 67, 111, 115, 143

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: 591 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_REGULATION_OF_RESPIRATORY_BURST, RNGTGGGC_UNKNOWN, CREL_01, E2F_Q4_01, GOBP_RIBOSOME_BIOGENESIS, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, MODULE_151, GCM_NPM1, GOBP_MATURATION_OF_SSU_RRNA

GO Biological Process (15): ribosomal small subunit assembly (GO:0000028), maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462), cytoplasmic translation (GO:0002181), monocyte chemotaxis (GO:0002548), rRNA processing (GO:0006364), translation (GO:0006412), nucleolus organization (GO:0007000), erythrocyte differentiation (GO:0030218), maturation of SSU-rRNA (GO:0030490), killing of cells of another organism (GO:0031640), ribosomal small subunit biogenesis (GO:0042274), defense response to Gram-negative bacterium (GO:0050829), positive regulation of respiratory burst involved in inflammatory response (GO:0060265), negative regulation of respiratory burst involved in inflammatory response (GO:0060266), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844)

GO Molecular Function (6): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), fibroblast growth factor binding (GO:0017134), protein kinase binding (GO:0019901), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (14): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), ribosome (GO:0005840), focal adhesion (GO:0005925), postsynaptic density (GO:0014069), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), small-subunit processome (GO:0032040), extracellular exosome (GO:0070062), nucleus (GO:0005634), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Translation	2
Nonsense-Mediated Decay (NMD)	2
Ribosome-associated quality control	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	1
rRNA processing in the nucleus and cytosol	1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1
Signaling by ROBO receptors	1
Cellular response to starvation	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
ribosomal small subunit biogenesis	2
ribosome biogenesis	2
respiratory burst involved in inflammatory response	2
regulation of respiratory burst involved in inflammatory response	2
ribosome	2
nuclear lumen	2
intracellular membraneless organelle	2
protein-RNA complex assembly	1
ribosome assembly	1
maturation of SSU-rRNA	1
translation	1
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
RNA processing	1
rRNA metabolic process	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
nucleus organization	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
rRNA processing	1
cell killing	1
disruption of cell in another organism	1
ribonucleoprotein complex biogenesis	1
defense response to bacterium	1
positive regulation of immune effector process	1
positive regulation of innate immune response	1
positive regulation of inflammatory response	1
positive regulation of multicellular organismal process	1
positive regulation of respiratory burst	1
negative regulation of immune effector process	1
negative regulation of innate immune response	1
negative regulation of inflammatory response	1

Protein interactions and networks

STRING

3895 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS19	C5AR1	P21730	986
RPS19	RPS24	P16632	975
RPS19	RPS20	P17075	955
RPS19	RPL35A	P18077	951
RPS19	RPS17	P08708	947
RPS19	RPL5	P46777	940
RPS19	RPS10	P46783	938
RPS19	RPL11	P25121	928
RPS19	RPS26	P02383	925
RPS19	RPS14	P06366	899
RPS19	RPS6	P08227	881
RPS19	RPS16	P17008	873
RPS19	RPS3	P23396	858
RPS19	RPS13	P19116	845
RPS19	RPS2	P15880	839

IntAct

287 interactions, top by confidence:

A	B	Type	Score
NOP10	DKC1	psi-mi:“MI:0914”(association)	0.890
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RPS19	RPS16	psi-mi:“MI:0915”(physical association)	0.670
LIN28A	IGF2BP3	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
RPS19	H1-5	psi-mi:“MI:0915”(physical association)	0.560
RPS19	SPG21	psi-mi:“MI:0915”(physical association)	0.560
RPS19	HTT	psi-mi:“MI:0915”(physical association)	0.560
RPS19	ATXN1	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
PRPF31	SSB	psi-mi:“MI:0914”(association)	0.510
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
VDAC2	RPS19	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (947): RPS19 (Affinity Capture-MS), RPS19 (Affinity Capture-MS), RPS19 (Affinity Capture-MS), RPS19 (Affinity Capture-MS), RPS19 (Affinity Capture-MS), ASCC2 (Co-fractionation), KPNA1 (Co-fractionation), PRPF4 (Co-fractionation), RPL10 (Co-fractionation), RPL10A (Co-fractionation), RPL12 (Co-fractionation), RPL13 (Co-fractionation), RPL13A (Co-fractionation), RPL14 (Co-fractionation), RPL18 (Co-fractionation)

ESM2 similar proteins: A0A1D8PK61, A0RVY8, A2SPL7, A3CT12, A7I5Q4, A9BCN4, B8GKE8, G1TN62, O15631, O18650, O27653, O28210, P07280, P07281, P17074, P24494, P27073, P33106, P39018, P39019, P39698, P40978, P54057, P58234, P61155, P79016, Q252W6, Q29308, Q2FSG2, Q2S3Q0, Q32PD5, Q32RN2, Q54X51, Q5JGN5, Q5R8M9, Q6ME50, Q7KS38, Q8ITC3, Q8SQS8, Q8T5Z4

Diamond homologs: A0A1D8PK61, G1TN62, O15631, O18650, O27653, O28210, O59041, P07280, P07281, P17074, P19952, P24494, P27073, P39018, P39019, P39698, P40978, P54057, P58234, P61155, P79016, Q29308, Q32PD5, Q54X51, Q5JGN5, Q5R8M9, Q7KS38, Q8ITC3, Q8SQS8, Q8T5Z4, Q90YQ4, Q94613, Q97CU4, Q9CZX8, Q9DFR5, Q9FNP8, Q9LF30, Q9SGA6, Q9V0G8, Q9Y0H3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PIM1	up-regulates	RPS19	phosphorylation
PIM	up-regulates	RPS19	phosphorylation
RPS19	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 198 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	11	24.2×	1e-11
Eukaryotic Translation Initiation	10	22.1×	4e-10
Cap-dependent Translation Initiation	10	22.1×	4e-10
Formation of the ternary complex, and subsequently, the 43S complex	13	20.0×	2e-12
Eukaryotic Translation Elongation	10	19.9×	1e-09
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	10	19.4×	1e-09
Ribosomal scanning and start codon recognition	14	19.0×	4e-13
Nonsense-Mediated Decay (NMD)	11	18.3×	4e-10

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	21	22.4×	8e-20
stress granule assembly	6	20.8×	8e-05
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	5	19.4×	7e-04
translational initiation	7	14.4×	1e-04
ribosomal small subunit biogenesis	11	14.4×	1e-07
activation of innate immune response	5	13.8×	3e-03
regulation of translational initiation	5	13.4×	3e-03
ribosomal large subunit biogenesis	5	12.7×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	57
Likely pathogenic	24
Uncertain significance	95
Likely benign	74
Benign	15

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1006194	NM_001022.4(RPS19):c.53T>C (p.Leu18Pro)	Pathogenic
1013167	NM_001022.4(RPS19):c.372dup (p.Pro125fs)	Pathogenic
1071332	NM_001022.4(RPS19):c.185G>C (p.Arg62Pro)	Pathogenic
1072173	NM_001022.4(RPS19):c.58_61dup (p.Phe21fs)	Pathogenic
1323536	NM_001022.4(RPS19):c.403_404del (p.Ala135fs)	Pathogenic
1369946	NM_001022.4(RPS19):c.173-1G>T	Pathogenic
1459369	NC_000019.9:g.(?42363988)(42375445_?)del	Pathogenic
1687347	NM_001022.4(RPS19):c.296_297del (p.Val99fs)	Pathogenic
1732047	NM_001022.4(RPS19):c.34C>T (p.Gln12Ter)	Pathogenic
1735592	NM_001022.4(RPS19):c.385dup (p.Arg129fs)	Pathogenic
1736908	NM_001022.4(RPS19):c.3G>C (p.Met1Ile)	Pathogenic
1776783	NM_001022.4(RPS19):c.162C>G (p.Tyr54Ter)	Pathogenic
1782649	NM_001022.4(RPS19):c.191T>C (p.Leu64Pro)	Pathogenic
1787597	NM_001022.4(RPS19):c.21del (p.Asp8fs)	Pathogenic
1797274	NM_001022.4(RPS19):c.288dup (p.Lys97fs)	Pathogenic
2007213	NM_001022.4(RPS19):c.347del (p.Asp116fs)	Pathogenic
2129014	NM_001022.4(RPS19):c.101del (p.Val34fs)	Pathogenic
2138299	NM_001022.4(RPS19):c.94G>T (p.Glu32Ter)	Pathogenic
2138300	NM_001022.4(RPS19):c.166C>T (p.Arg56Ter)	Pathogenic
2412767	NM_001022.4(RPS19):c.316del (p.Ala106fs)	Pathogenic
2423481	NC_000019.9:g.(?42363988)(42364925_?)del	Pathogenic
242804	NM_001022.4(RPS19):c.43G>T (p.Val15Phe)	Pathogenic
2690490	NM_001022.4(RPS19):c.376C>T (p.Gln126Ter)	Pathogenic
2736899	NM_001022.4(RPS19):c.357-2A>G	Pathogenic
2780439	NM_001022.4(RPS19):c.1A>C (p.Met1Leu)	Pathogenic
3248435	NC_000019.9:g.(?42373081)(42373843_?)del	Pathogenic
3255048	NM_001022.4(RPS19):c.24_31dup (p.Gln11delinsProTer)	Pathogenic
3348205	NM_001022.4(RPS19):c.31C>T (p.Gln11Ter)	Pathogenic
3660144	NM_001022.4(RPS19):c.313C>T (p.Gln105Ter)	Pathogenic
3677180	NM_001022.4(RPS19):c.407dup (p.Gln137fs)	Pathogenic

SpliceAI

834 predictions. Top by Δscore:

Variant	Effect	Δscore
19:41860769:CCTCA:C	acceptor_loss	1.0000
19:41860771:TCA:T	acceptor_loss	1.0000
19:41860773:A:AG	acceptor_gain	1.0000
19:41860773:AGAT:A	acceptor_gain	1.0000
19:41860774:G:GA	acceptor_gain	1.0000
19:41860774:GA:G	acceptor_gain	1.0000
19:41860774:GAT:G	acceptor_gain	1.0000
19:41860774:GATG:G	acceptor_gain	1.0000
19:41860774:GATGC:G	acceptor_gain	1.0000
19:41860841:AAAAA:A	donor_gain	1.0000
19:41860842:AAAA:A	donor_gain	1.0000
19:41860843:AAA:A	donor_gain	1.0000
19:41860843:AAAG:A	donor_loss	1.0000
19:41860844:AA:A	donor_gain	1.0000
19:41860845:AGTG:A	donor_loss	1.0000
19:41860846:G:GG	donor_gain	1.0000
19:41860846:GTG:G	donor_loss	1.0000
19:41861103:T:A	acceptor_gain	1.0000
19:41861104:G:A	acceptor_gain	1.0000
19:41861107:CTTA:C	acceptor_loss	1.0000
19:41861108:TTA:T	acceptor_loss	1.0000
19:41861109:TA:T	acceptor_loss	1.0000
19:41861110:A:AG	acceptor_gain	1.0000
19:41861110:A:C	acceptor_loss	1.0000
19:41861110:AG:A	acceptor_gain	1.0000
19:41861111:G:GT	acceptor_gain	1.0000
19:41861111:GG:G	acceptor_gain	1.0000
19:41861111:GGT:G	acceptor_gain	1.0000
19:41861111:GGTC:G	acceptor_gain	1.0000
19:41861111:GGTCC:G	acceptor_gain	1.0000

AlphaMissense

931 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:41860835:T:C	F21L	0.999
19:41860837:C:A	F21L	0.999
19:41860837:C:G	F21L	0.999
19:41861137:T:A	W33R	0.999
19:41861137:T:C	W33R	0.999
19:41861194:T:A	W52R	0.999
19:41861194:T:C	W52R	0.999
19:41861210:C:A	A57D	0.999
19:41869031:C:A	A58D	0.999
19:41869070:G:A	G71E	0.999
19:41869096:G:T	G80W	0.999
19:41869097:G:A	G80E	0.999
19:41869097:G:T	G80V	0.999
19:41869721:G:A	G127R	0.999
19:41869721:G:C	G127R	0.999
19:41869746:C:A	A135D	0.999
19:41869096:G:A	G80R	0.998
19:41869096:G:C	G80R	0.998
19:41869132:T:C	F92L	0.998
19:41869134:C:A	F92L	0.998
19:41869134:C:G	F92L	0.998
19:41869174:G:C	A106P	0.998
19:41869703:C:A	R121S	0.998
19:41869722:G:A	G127E	0.998
19:41869734:T:C	L131P	0.998
19:41869736:G:C	D132H	0.998
19:41860829:G:C	A19P	0.997
19:41860839:T:C	L22P	0.997
19:41861196:G:C	W52C	0.997
19:41861196:G:T	W52C	0.997

dbSNP variants (sampled 300 via entrez): RS1000036981 (19:41867686 T>A), RS1000819929 (19:41872669 G>A,C,T), RS1001790042 (19:41859465 G>A), RS1001944144 (19:41865080 C>T), RS1002325824 (19:41868680 A>G), RS1002383133 (19:41868896 C>A,T), RS1002465586 (19:41861005 C>A,G,T), RS1002918473 (19:41871253 C>A,G,T), RS1003335379 (19:41870023 A>T), RS1003386253 (19:41870318 G>A), RS1003490520 (19:41864886 G>A), RS1003572639 (19:41865763 A>G), RS1004810150 (19:41864829 G>A), RS1004840871 (19:41864575 T>A,C), RS1005518799 (19:41866825 G>A,C)

Disease associations

OMIM: gene MIM:603474 | disease phenotypes: MIM:105650

GenCC curated gene-disease

Disease	Classification	Inheritance
Diamond-Blackfan anemia 1	Definitive	Autosomal dominant
Diamond-Blackfan anemia	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Diamond-Blackfan anemia	Definitive	AD

Mondo (3): Diamond-Blackfan anemia (MONDO:0015253), Diamond-Blackfan anemia 1 (MONDO:0007110), hepatoblastoma (MONDO:0018666)

Orphanet (2): Diamond-Blackfan anemia (Orphanet:124), Hepatoblastoma (Orphanet:449)

HPO phenotypes

94 total (30 of 94 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000089	Renal hypoplasia
HP:0000104	Renal agenesis
HP:0000119	Abnormality of the genitourinary system
HP:0000175	Cleft palate
HP:0000185	Cleft soft palate
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000234	Abnormality of the head
HP:0000252	Microcephaly
HP:0000270	Delayed cranial suture closure
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000457	Depressed nasal ridge
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000519	Developmental cataract
HP:0000774	Narrow chest
HP:0000878	11 pairs of ribs
HP:0000912	Sprengel anomaly

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_14	Brain morphology (MOSTest)	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D029503	Anemia, Diamond-Blackfan	C15.378.050.085.080.090; C15.378.050.750.500; C15.378.190.223.500.500.090; C16.320.077.090
D018197	Hepatoblastoma	C04.557.435.380
C567302	Diamond-Blackfan Anemia 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066908 (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

52 potent at pChembl≥5 of 56 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.70	Kd	199.2	nM	CHEMBL5653589
6.70	ED50	199.2	nM	CHEMBL5653589
6.58	Kd	265	nM	MOLIBRESIB
6.52	IC50	300	nM	CHEMBL4109308
6.50	IC50	320	nM	MOLIBRESIB
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
6.19	Kd	645.2	nM	CHEMBL3752910
6.19	ED50	645.2	nM	CHEMBL3752910
6.16	IC50	690	nM	CHEMBL4130157
6.15	IC50	710	nM	CHEMBL4108338
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	IC50	900	nM	CHEMBL4126894
6.05	IC50	900	nM	CHEMBL4126496
6.04	IC50	920	nM	CHEMBL4554909
5.97	IC50	1060	nM	CHEMBL4128388
5.89	IC50	1290	nM	CHEMBL4130157
5.86	IC50	1370	nM	CHEMBL4107559
5.84	IC50	1440	nM	CHEMBL4108338
5.81	IC50	1540	nM	CHEMBL4534859
5.76	IC50	1730	nM	CHEMBL4534859
5.69	IC50	2050	nM	CHEMBL4566239
5.68	IC50	2080	nM	CHEMBL4446635
5.66	IC50	2210	nM	CHEMBL4446635
5.66	EC50	2200	nM	CHEMBL4464929
5.64	IC50	2270	nM	CHEMBL4533299
5.63	IC50	2330	nM	CHEMBL4566239
5.62	IC50	2380	nM	CHEMBL4128388
5.58	IC50	2630	nM	CHEMBL4128250
5.55	IC50	2820	nM	CHEMBL4127458
5.53	IC50	2970	nM	CHEMBL4127311
5.51	IC50	3080	nM	CHEMBL4126072
5.46	IC50	3500	nM	CHEMBL4525277
5.44	IC50	3630	nM	CHEMBL4469712
5.39	IC50	4100	nM	CHEMBL4128560
5.37	IC50	4300	nM	CHEMBL4127016
5.36	IC50	4380	nM	CHEMBL4527910
5.16	IC50	7000	nM	CHEMBL4109308
5.13	IC50	7400	nM	CHLORAMPHENICOL SULFATE SALT
5.09	IC50	8040	nM	CHEMBL4128250
5.08	IC50	8370	nM	CHEMBL4128250
5.03	IC50	9320	nM	CHEMBL4127016

PubChem BioAssay actives

50 with measured affinity, of 216 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149292: Binding affinity to human RPS19 incubated for 45 mins by Kinobead based pull down assay	kd	0.1992	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	2179192: Binding affinity against RPS19 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.2650	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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149292: Binding affinity to human RPS19 incubated for 45 mins by Kinobead based pull down assay	kd	0.6452	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.6900	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-5-(triazolo[4,5-b]pyridin-3-yl)pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.7100	uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylpiperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.9200	uM
N-isoquinolin-1-yl-4-(1-methylpyrazol-4-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	1.0600	uM
N-isoquinolin-1-yl-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	1.5400	uM
N-(3-methyl-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.0500	uM
N-(3-chloro-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	2.0800	uM
N-(5,8-dihydroisoquinolin-1-yl)-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1584424: Inhibition of human 80S ribosome-mediated PCSK9 translation expressed in CHO-K1 cells assessed as reduction in PCSK9 secretion	ec50	2.2000	uM
N-isoquinolin-1-yl-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.6300	uM
N-(3-chloro-2-pyridinyl)-4-(6-methylpyrazin-2-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.8200	uM
N-(3-chloro-2-pyridinyl)-4-[6-(dimethylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.9700	uM
N-(3-chloro-2-pyridinyl)-4-[6-(methylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	3.0800	uM
N-isoquinolin-1-yl-4-(6-methyl-1,2-benzoxazol-3-yl)-N-[(3R)-piperidin-3-yl]piperazine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	3.5000	uM
N-(3-methylpyrazin-2-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	3.6300	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-6-(triazolo[4,5-b]pyridin-3-yl)pyridine-3-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.1000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazin-2-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.3000	uM
4-(2-fluorophenyl)-N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	4.3800	uM
2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide;sulfuric acid	717551: Inhibition of mitochondrial ribosome-mediated protein synthesis in human HeLa cells assessed as {35S]methionine incorporation by autoradiography	ic50	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
Caffeine	decreases expression, decreases phosphorylation	2
Cadmium Chloride	increases expression	2
bisphenol F	increases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization, increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
sodium arsenite	decreases expression, increases activity	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
N-benzyloxycarbonylprolylprolinal	increases expression	1
artenimol	affects binding	1
arsenic trichloride	affects cotreatment, decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
fenbuconazole	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
enzalutamide	affects expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Bortezomib	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Aspirin	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1

ChEMBL screening assays

97 unique, capped per target: 97 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

Cellosaurus cell lines

5 cell lines: 5 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C6ST	STJUDEi004-A	Induced pluripotent stem cell	Female
CVCL_C6SU	STJUDEi004-A-1	Induced pluripotent stem cell	Female
CVCL_C6SV	STJUDEi005-A	Induced pluripotent stem cell	Female
CVCL_C6SW	STJUDEi005-A-1	Induced pluripotent stem cell	Female
CVCL_C7XP	CSCRi006-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00673608	PHASE4	COMPLETED	Magnetic Resonance Imaging (MRI) Assessments of the Heart and Liver Iron Load in Patients With Transfusion Induced Iron Overload
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT00235391	PHASE3	COMPLETED	Expanded Access of Deferasirox to Patients With Congenital Disorders of Red Blood Cells and Chronic Iron Overload
NCT03017326	PHASE3	ACTIVE_NOT_RECRUITING	Paediatric Hepatic International Tumour Trial
NCT03533582	PHASE3	ACTIVE_NOT_RECRUITING	Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
NCT04478292	PHASE3	RECRUITING	A Multi-institutional Study for Treatment of Children With Newly Diagnosed Hepatoblastoma Using a Modified PHITT Strategy
NCT00001962	PHASE2	TERMINATED	A Study to Determine Whether Therapy With Daclizumab Will Benefit Patients With Bone Marrow Failure
NCT00011505	PHASE2	COMPLETED	Mobilization of Stem Cells With G-CSF for Collection From Patients With Diamond-Blackfan Anemia
NCT00301834	PHASE2	COMPLETED	Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
NCT00957931	PHASE2	COMPLETED	Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT02386267	PHASE2	UNKNOWN	L-leucine in Diamond Blackfan Anemia Patients
NCT02512679	PHASE2	TERMINATED	Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells
NCT03333486	PHASE2	TERMINATED	Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
NCT04099966	PHASE2	RECRUITING	AlloSCT for Malignant and Non-malignant Hematologic Diseases Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion
NCT04965597	PHASE2	COMPLETED	Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
NCT01154816	PHASE2	COMPLETED	Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia
NCT02011126	PHASE2	WITHDRAWN	Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT05302921	PHASE2	COMPLETED	Neoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors
NCT06638931	PHASE2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT07300449	PHASE2	RECRUITING	A Prospective Multicenter Clinical Study of SCCG Protocol and ctDNA 5hmc in Predicting the Chemotherapy Sensitivity and Monitoring the Recurrence and Metastasis of Hepatoblastoma in Children and Adolescents
NCT01586455	PHASE1	COMPLETED	Human Placental-Derived Stem Cell Transplantation
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT01331135	PHASE1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT02390843	PHASE1	COMPLETED	Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors
NCT03618381	PHASE1	ACTIVE_NOT_RECRUITING	EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults