RPL19

Summary

RPL19 (ribosomal protein L19, HGNC:10312) is a protein-coding gene on chromosome 17q12, encoding Large ribosomal subunit protein eL19 (P84098). Component of the large ribosomal subunit. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L19E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6143 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 154 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_000981

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10312
Approved symbol	RPL19
Name	ribosomal protein L19
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ27452, MGC71997, DKFZp779D216, L19, eL19
Ensembl gene	ENSG00000108298
Ensembl biotype	protein_coding
OMIM	180466
Entrez	6143

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 17 protein_coding, 4 retained_intron, 4 nonsense_mediated_decay

ENST00000225430, ENST00000577741, ENST00000579260, ENST00000579374, ENST00000582193, ENST00000585199, ENST00000678012, ENST00000678147, ENST00000678189, ENST00000678573, ENST00000678609, ENST00000678791, ENST00000679038, ENST00000869076, ENST00000869077, ENST00000912393, ENST00000912394, ENST00000912395, ENST00000912396, ENST00000912397, ENST00000912398, ENST00000912399, ENST00000912400, ENST00000912401, ENST00000912402

RefSeq mRNA: 2 — MANE Select: NM_000981 NM_000981, NM_001330200

CCDS: CCDS42312, CCDS82113

Canonical transcript exons

ENST00000225430 — 6 exons

Exon	Start	End
ENSE00000718546	39202317	39202439
ENSE00000718555	39202989	39203109
ENSE00001533686	39200283	39200349
ENSE00003563167	39204077	39204187
ENSE00003563881	39201213	39201319
ENSE00003832753	39204525	39204732

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.5426 / max 407.0477, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160556	27.9724	1810
160555	10.1765	1778
160557	3.3369	1419
160559	1.8908	998
160558	0.1660	64

Top tissues by expression

301 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	99.93	gold quality
calcaneal tendon	UBERON:0003701	99.91	gold quality
granulocyte	CL:0000094	99.90	gold quality
lymph node	UBERON:0000029	99.89	gold quality
left ovary	UBERON:0002119	99.88	gold quality
upper leg skin	UBERON:0004262	99.88	gold quality
tendon	UBERON:0000043	99.87	gold quality
endocervix	UBERON:0000458	99.87	gold quality
skin of leg	UBERON:0001511	99.87	gold quality
skin of hip	UBERON:0001554	99.87	gold quality
right ovary	UBERON:0002118	99.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.87	gold quality
pituitary gland	UBERON:0000007	99.86	gold quality
zone of skin	UBERON:0000014	99.86	gold quality
ovary	UBERON:0000992	99.86	gold quality
mucosa of stomach	UBERON:0001199	99.86	gold quality
skin of abdomen	UBERON:0001416	99.86	gold quality
adenohypophysis	UBERON:0002196	99.86	gold quality
body of uterus	UBERON:0009853	99.86	gold quality
metanephros cortex	UBERON:0010533	99.86	gold quality
right lobe of thyroid gland	UBERON:0001119	99.85	gold quality
left lobe of thyroid gland	UBERON:0001120	99.85	gold quality
right uterine tube	UBERON:0001302	99.85	gold quality
left uterine tube	UBERON:0001303	99.85	gold quality
superficial temporal artery	UBERON:0001614	99.85	gold quality
gall bladder	UBERON:0002110	99.85	gold quality
ectocervix	UBERON:0012249	99.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.85	gold quality
embryo	UBERON:0000922	99.84	gold quality
left adrenal gland	UBERON:0001234	99.84	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	7786.23
E-CURD-88	yes	7221.57
E-MTAB-10042	yes	6011.71
E-MTAB-6678	yes	3534.34
E-CURD-122	yes	109.70
E-MTAB-9221	yes	55.02
E-CURD-112	yes	30.34
E-GEOD-137537	yes	29.49
E-HCAD-9	yes	29.15
E-MTAB-7316	yes	16.39
E-MTAB-9543	yes	15.16
E-HCAD-35	yes	9.90
E-CURD-55	no	8734.79
E-MTAB-6653	no	8565.44
E-HCAD-32	no	7826.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• The increased RPL19 expression to be highly predictive of shorter patient survival (P < 0.05), revealing RPL19 to be a sensitive predictor of prostate cancer progression. (PMID:16609016)
• L19-IL2 efficiently inhibits the growth of orthotopic pancreatic cancer (PMID:18676770)
• RPL19 is a novel overexpressed antigen which may therefore be a useful candidate as a target for specific immunotherapy. (PMID:19799608)
• L19-SIP shows a time and blood-flow dependent microvascular biodistribution process with angiogenic sprouts as preferential binding sites followed by secondary extravasation of the antibody (PMID:21396810)
• posttranscriptional silencing of gene RPL19 using RNAi not only abrogates the malignant phenotype of PC-3M prostate cancer cells but is selective with respect to transcription and translation of other genes (PMID:21799931)
• Our findings suggest that upregulation of RPL19 induces ER stress, resulting in increased sensitivity to ER stress and enhanced cell death in MCF7 breast cancer cells. (PMID:24950402)
• A three-gene signature and clinical outcome in pediatric acute myeloid leukemia. (PMID:32862280)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl19	ENSDARG00000013307
mus_musculus	Rpl19	ENSMUSG00000017404
rattus_norvegicus	Rpl19l4	ENSRNOG00000012088
drosophila_melanogaster	RpL19	FBGN0285950
caenorhabditis_elegans	rpl-19	WBGENE00004431

Protein

Protein identifiers

Large ribosomal subunit protein eL19 — P84098 (reviewed: P84098)

Alternative names: 60S ribosomal protein L19

All UniProt accessions (8): P84098, A0A7I2V2L0, A0A7I2V4U6, A0A7I2V512, A0A7I2V638, A0A7I2YQG2, J3KTE4, J3QR09

UniProt curated annotations — full annotation on UniProt →

Function. Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.

Subunit / interactions. Component of the large ribosomal subunit.

Subcellular location. Cytoplasm.

Post-translational modifications. Citrullinated by PADI4.

Similarity. Belongs to the eukaryotic ribosomal protein eL19 family.

RefSeq proteins (2): NP_000972, NP_001317129 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000196	Ribosomal_eL19_dom	Domain
IPR015972	Ribosomal_eL19_dom1	Homologous_superfamily
IPR023638	Ribosomal_eL19_CS	Conserved_site
IPR033935	Ribosomal_eL19_euk	Domain
IPR035970	60S_ribosomal_eL19_sf	Homologous_superfamily
IPR039547	Ribosomal_eL19	Family
IPR057259	Ribosomal_L19e	Domain
IPR057260	Ribosomal_L19e_C	Domain

Pfam: PF01280, PF25476

UniProt features (10 total): modified residue 6, chain 1, region of interest 1, compositionally biased region 1, cross-link 1

Structure

Experimental structures (PDB)

190 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8A3D	ELECTRON MICROSCOPY	1.67
8GLP	ELECTRON MICROSCOPY	1.67
8QYX	ELECTRON MICROSCOPY	1.78
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8QFD	ELECTRON MICROSCOPY	2.2
8YOP	ELECTRON MICROSCOPY	2.2
9GUL	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
7OW7	ELECTRON MICROSCOPY	2.4
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
8FLE	ELECTRON MICROSCOPY	2.48
9P8B	ELECTRON MICROSCOPY	2.48
7XNY	ELECTRON MICROSCOPY	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P84098-F1	94.75	0.93

Functional residue map

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

Post-translational modifications (7): 5, 13, 16, 38, 164, 187, 181

Function

Pathways and Gene Ontology

Reactome pathways

16 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-72689	Formation of a pool of free 40S subunits
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-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-9954709	Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide
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

MSigDB gene sets: 270 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_CYTOPLASMIC_TRANSLATION, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, MODULE_151, GNF2_TPT1, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCM_NPM1, MORF_UBE2I, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, USF_C

GO Biological Process (2): cytoplasmic translation (GO:0002181), translation (GO:0006412)

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

GO Cellular Component (10): nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), synapse (GO:0045202), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Ribosome-associated quality control	3
Translation	2
Cap-dependent Translation Initiation	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
Signaling by ROBO receptors	1
Cellular response to starvation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
ribosome	2
intracellular membraneless organelle	2
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
nucleic acid binding	1
structural molecule activity	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
cell junction	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

294 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
HTT	RPL19	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	RPL19	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
E4F1	ZBTB24	psi-mi:“MI:0914”(association)	0.530
ZCRB1	DKC1	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
MRPL50	GTPBP10	psi-mi:“MI:0914”(association)	0.530
H2AC20	PPM1G	psi-mi:“MI:0914”(association)	0.530
RPL19	TERF1	psi-mi:“MI:0915”(physical association)	0.510
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
PA2G4	RPL35	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (937): RPL19 (Affinity Capture-MS), RPL19 (Affinity Capture-MS), RPL19 (Affinity Capture-MS), RPL19 (Affinity Capture-MS), RPL10 (Co-fractionation), RPL10A (Co-fractionation), RPL11 (Co-fractionation), RPL12 (Co-fractionation), RPL13 (Co-fractionation), RPL13A (Co-fractionation), RPL15 (Co-fractionation), RPL17 (Co-fractionation), RPL19 (Co-fractionation), RPL19 (Co-fractionation), RPL19 (Co-fractionation)

ESM2 similar proteins: A0A1D8PK40, A9KD35, A9NAM0, B6J267, B6J5C8, D0VWQ5, G1TFM5, G1TYL6, O02639, O05639, O26129, O42699, O65055, P05734, P0CX82, P0CX83, P0DJ15, P0DJ60, P14024, P14329, P24050, P26784, P26785, P36241, P46782, P49693, P84098, P84099, P84100, P97461, Q04EH1, Q27389, Q3B6E3, Q3T0W9, Q5AB87, Q5E988, Q5RB99, Q6JWW5, Q6P5L3, Q6YPI5

Diamond homologs: A0A1D8PK40, B1L784, D0VWQ5, G1TYL6, O02639, O05639, O26129, O28372, O42699, O59437, P05734, P0CX82, P0CX83, P0DJ60, P14024, P14119, P14329, P36241, P49693, P54043, P84098, P84099, P84100, Q08066, Q3IMX0, Q3T0W9, Q5JJG6, Q5RB99, Q6P5L3, Q7ZYS1, Q8HXN9, Q8U016, Q90YU8, Q9HPB6, Q9LUQ6, Q9SRX2, Q9UX89, Q9V1V3, Q9YF93

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL19	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 193 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
Eukaryotic Translation Initiation	8	17.6×	4e-07
Cap-dependent Translation Initiation	8	17.6×	4e-07
SARS-CoV-1 modulates host translation machinery	8	17.6×	4e-07
Eukaryotic Translation Elongation	8	15.9×	8e-07
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	8	15.5×	9e-07
Formation of the ternary complex, and subsequently, the 43S complex	10	15.4×	3e-08
Eukaryotic Translation Termination	17	14.6×	2e-13
Peptide chain elongation	16	14.5×	6e-13

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	18	19.1×	1e-15
ribosomal large subunit biogenesis	6	15.2×	6e-04
rRNA processing	18	14.6×	1e-13
ribosomal small subunit biogenesis	11	14.3×	8e-08
translation	23	13.5×	1e-16
translational initiation	6	12.3×	1e-03
intrinsic apoptotic signaling pathway	6	12.3×	1e-03
negative regulation of translation	8	9.0×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	83
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

628 predictions. Top by Δscore:

Variant	Effect	Δscore
17:39201211:A:AG	acceptor_gain	1.0000
17:39201211:AGTAT:A	acceptor_gain	1.0000
17:39201212:G:GT	acceptor_gain	1.0000
17:39201212:GT:G	acceptor_gain	1.0000
17:39201212:GTA:G	acceptor_gain	1.0000
17:39201212:GTAT:G	acceptor_gain	1.0000
17:39201212:GTATG:G	acceptor_gain	1.0000
17:39201315:CTCCC:C	donor_gain	1.0000
17:39201316:TCCC:T	donor_gain	1.0000
17:39201317:CCC:C	donor_gain	1.0000
17:39201320:G:GG	donor_gain	1.0000
17:39201324:G:GG	donor_gain	1.0000
17:39202312:CCCA:C	acceptor_loss	1.0000
17:39202313:CCAG:C	acceptor_loss	1.0000
17:39202314:CAG:C	acceptor_loss	1.0000
17:39202315:A:AG	acceptor_gain	1.0000
17:39202315:AG:A	acceptor_gain	1.0000
17:39202316:G:GT	acceptor_gain	1.0000
17:39202316:GG:G	acceptor_gain	1.0000
17:39202316:GGT:G	acceptor_gain	1.0000
17:39202316:GGTC:G	acceptor_gain	1.0000
17:39202316:GGTCA:G	acceptor_gain	1.0000
17:39202435:CATAG:C	donor_gain	1.0000
17:39202436:ATAG:A	donor_gain	1.0000
17:39202437:TAG:T	donor_gain	1.0000
17:39202438:AG:A	donor_gain	1.0000
17:39202438:AGGTA:A	donor_loss	1.0000
17:39202439:GG:G	donor_gain	1.0000
17:39202439:GGTA:G	donor_loss	1.0000
17:39202440:G:GA	donor_loss	1.0000

AlphaMissense

1291 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:39201233:G:T	R9M	1.000
17:39201239:C:A	A11D	1.000
17:39201260:G:A	G18D	1.000
17:39201260:G:T	G18V	1.000
17:39201272:T:A	V22D	1.000
17:39201274:T:A	W23R	1.000
17:39201274:T:C	W23R	1.000
17:39201310:G:C	A35P	1.000
17:39201311:C:A	A35D	1.000
17:39202335:T:C	L44P	1.000
17:39202350:T:C	L49P	1.000
17:39202353:T:A	I50N	1.000
17:39202421:G:C	G73R	1.000
17:39202422:G:A	G73D	1.000
17:39202433:G:C	G77R	1.000
17:39202439:G:C	G79R	1.000
17:39202989:G:A	G79D	1.000
17:39202989:G:T	G79V	1.000
17:39203000:G:C	G83R	1.000
17:39203001:G:A	G83D	1.000
17:39203001:G:T	G83V	1.000
17:39203036:T:A	W95R	1.000
17:39203036:T:C	W95R	1.000
17:39203052:G:T	R100M	1.000
17:39203067:T:C	L105P	1.000
17:39203070:T:A	L106H	1.000
17:39204088:T:C	L123P	1.000
17:39204105:G:A	G129R	1.000
17:39204105:G:C	G129R	1.000
17:39204105:G:T	G129W	1.000

dbSNP variants (sampled 300 via entrez): RS1000091001 (17:39202650 C>A,G,T), RS1000112331 (17:39198512 C>T), RS1000540149 (17:39204397 T>G), RS1001012521 (17:39200084 A>C), RS1001497477 (17:39204055 C>G,T), RS1001609044 (17:39200116 G>A), RS1001659966 (17:39199893 A>G,T), RS1002108416 (17:39200680 C>A,G), RS1002417056 (17:39200896 T>C), RS1002611979 (17:39200801 G>C), RS1002665858 (17:39200636 G>A), RS1003517166 (17:39202072 G>A), RS1004642703 (17:39202033 G>A), RS1005028760 (17:39201679 T>C), RS1006019958 (17:39203253 C>T)

Disease associations

OMIM: gene MIM:180466 | disease phenotypes: MIM:105650

GenCC curated gene-disease

Mondo (1): Diamond-Blackfan anemia (MONDO:0015253)

Orphanet (1): Diamond-Blackfan anemia (Orphanet:124)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008916_86	Asthma	2.000000e-14

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067554 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds).

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

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

ChEMBL bioactivities

48 potent at pChembl≥5 of 52 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.52	IC50	300	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4574496
6.41	IC50	390	nM	CHEMBL4126894
6.39	IC50	410	nM	CHEMBL4114159
6.35	IC50	450	nM	CHEMBL4126496
6.30	IC50	500	nM	CHEMBL4574496
6.30	IC50	500	nM	CHEMBL4560206
6.16	IC50	690	nM	CHEMBL4130157
6.15	IC50	710	nM	CHEMBL4108338
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	IC50	900	nM	CHEMBL4126894
6.05	IC50	900	nM	CHEMBL4126496
6.04	IC50	920	nM	CHEMBL4554909
5.97	IC50	1060	nM	CHEMBL4128388
5.89	IC50	1290	nM	CHEMBL4130157
5.86	IC50	1370	nM	CHEMBL4107559
5.84	IC50	1440	nM	CHEMBL4108338
5.81	IC50	1540	nM	CHEMBL4534859
5.76	IC50	1730	nM	CHEMBL4534859
5.69	IC50	2050	nM	CHEMBL4566239
5.68	IC50	2080	nM	CHEMBL4446635
5.66	IC50	2210	nM	CHEMBL4446635
5.66	EC50	2200	nM	CHEMBL4464929
5.64	IC50	2270	nM	CHEMBL4533299
5.63	IC50	2330	nM	CHEMBL4566239
5.62	IC50	2380	nM	CHEMBL4128388
5.58	IC50	2630	nM	CHEMBL4128250
5.55	IC50	2820	nM	CHEMBL4127458
5.53	IC50	2970	nM	CHEMBL4127311
5.53	Kd	2933	nM	CHEMBL3752910
5.53	ED50	2933	nM	CHEMBL3752910
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

47 with measured affinity, of 207 total; 27 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1585498: Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method	ic50	0.3000	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-3-[4-(triazolo[4,5-b]pyridin-3-yl)phenyl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3800	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3900	uM
N-(3-chloro-2-pyridinyl)-4-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4100	uM
N-(3-chloro-2-pyridinyl)-4-(5-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4500	uM
N-(1-methylpyrrolo[2,3-c]pyridin-7-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.5000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.6900	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-5-(triazolo[4,5-b]pyridin-3-yl)pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.7100	uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylpiperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.9200	uM
N-isoquinolin-1-yl-4-(1-methylpyrazol-4-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	1.0600	uM
N-isoquinolin-1-yl-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	1.5400	uM
N-(3-methyl-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.0500	uM
N-(3-chloro-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	2.0800	uM
N-(5,8-dihydroisoquinolin-1-yl)-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1584424: Inhibition of human 80S ribosome-mediated PCSK9 translation expressed in CHO-K1 cells assessed as reduction in PCSK9 secretion	ec50	2.2000	uM
N-isoquinolin-1-yl-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.6300	uM
N-(3-chloro-2-pyridinyl)-4-(6-methylpyrazin-2-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.8200	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149250: Binding affinity to human RPL19 incubated for 45 mins by Kinobead based pull down assay	kd	2.9326	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression, decreases reaction, increases abundance	4
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases activity	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Rotenone	decreases expression, increases expression	2
ginger extract	increases abundance, increases expression, decreases reaction	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization, increases expression	1
arsenite	affects binding, increases reaction	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	decreases expression	1
azoxystrobin	increases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
pyrimidifen	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects expression	1
Benzo(a)pyrene	increases methylation	1
Benztropine	increases expression	1
Clozapine	increases expression	1
Cuprizone	affects cotreatment, increases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1

ChEMBL screening assays

90 unique, capped per target: 90 binding

Representative assays (with source publication via chembl_document):

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

Clinical trials (associated diseases)

38 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
NCT00235391	PHASE3	COMPLETED	Expanded Access of Deferasirox to Patients With Congenital Disorders of Red Blood Cells and Chronic Iron Overload
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)
NCT01586455	PHASE1	COMPLETED	Human Placental-Derived Stem Cell Transplantation
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00176852	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Hemoglobinopathy
NCT00176878	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Bone Marrow Failure Syndromes
NCT00305708	PHASE1/PHASE2	COMPLETED	Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
NCT01362595	PHASE1/PHASE2	COMPLETED	Pilot Phase I/II Study of Amino Acid Leucine in Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia
NCT01419704	PHASE1/PHASE2	WITHDRAWN	Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
NCT01464164	PHASE1/PHASE2	TERMINATED	Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia
NCT01966367	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT02065869	PHASE1/PHASE2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03653338	PHASE1/PHASE2	RECRUITING	T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias
NCT03733249	PHASE1/PHASE2	TERMINATED	Long Term Follow-up Study for Patients Enrolled on the BP-004 Clinical Study
NCT03966053	PHASE1/PHASE2	TERMINATED	The Use of Trifluoperazine in Transfusion Dependent DBA
NCT00027274	Not specified	RECRUITING	Cancer in Inherited Bone Marrow Failure Syndromes
NCT00244010	Not specified	COMPLETED	Partially Matched Stem Cell Transplantation for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias
NCT00290628	Not specified	TERMINATED	Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer
NCT01114776	Not specified	COMPLETED	Multi-Center Study of Iron Overload: Pilot Study
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT01758042	Not specified	COMPLETED	Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders
NCT01913548	Not specified	COMPLETED	Multi-Center Study of Iron Overload: Survey Study (MCSIO)
NCT02179359	Not specified	TERMINATED	Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT07186179	Not specified	RECRUITING	Mobilization of CD34+ Peripheral Blood Stem Cells in Patients With Diamond Blackfan Anemia Syndrome (DBAS)