RPLP1

Summary

RPLP1 (ribosomal protein lateral stalk subunit P1, HGNC:10372) is a protein-coding gene on chromosome 15q23, encoding Large ribosomal subunit protein P1 (P05386). Plays an important role in the elongation step of protein synthesis. It is a common-essential gene (DepMap: required in 99.8% 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 phosphoprotein that is a component of the 60S subunit. The protein, which is a functional equivalent of the E. coli L7/L12 ribosomal protein, belongs to the L12P family of ribosomal proteins. It plays an important role in the elongation step of protein synthesis. Unlike most ribosomal proteins, which are basic, the encoded protein is acidic. Its C-terminal end is nearly identical to the C-terminal ends of the ribosomal phosphoproteins P0 and P2. The P1 protein can interact with P0 and P2 to form a pentameric complex consisting of P1 and P2 dimers, and a P0 monomer. The protein is located in the cytoplasm. Two alternatively spliced transcript variants that encode different proteins have 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 6176 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 17 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_001003

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10372
Approved symbol	RPLP1
Name	ribosomal protein lateral stalk subunit P1
Location	15q23
Locus type	gene with protein product
Status	Approved
Aliases	LP1, P1
Ensembl gene	ENSG00000137818
Ensembl biotype	protein_coding
OMIM	180520
Entrez	6176

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 2 retained_intron

ENST00000260379, ENST00000357790, ENST00000487304, ENST00000488122, ENST00000560274, ENST00000859700, ENST00000859701, ENST00000911445, ENST00000911446, ENST00000911447, ENST00000911448, ENST00000911449, ENST00000911451, ENST00000911452, ENST00000911453, ENST00000911454, ENST00000911455

RefSeq mRNA: 2 — MANE Select: NM_001003 NM_001003, NM_213725

CCDS: CCDS10233, CCDS10234

Canonical transcript exons

ENST00000260379 — 4 exons

Exon	Start	End
ENSE00000931693	69453647	69453721
ENSE00001824463	69452818	69453020
ENSE00001934065	69455428	69456205
ENSE00003566849	69455170	69455287

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1199.0855 / max 8845.1477, expressed in 1829 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147454	1197.7413	1829
147453	1.3442	662

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelium of bronchus	UBERON:0002031	99.99	gold quality
thymus	UBERON:0002370	99.98	gold quality
trachea	UBERON:0003126	99.97	gold quality
layer of synovial tissue	UBERON:0007616	99.96	gold quality
bone marrow cell	CL:0002092	99.93	gold quality
dorsal root ganglion	UBERON:0000044	99.93	gold quality
quadriceps femoris	UBERON:0001377	99.93	gold quality
vastus lateralis	UBERON:0001379	99.93	gold quality
endometrium epithelium	UBERON:0004811	99.93	gold quality
zone of skin	UBERON:0000014	99.91	gold quality
skin of leg	UBERON:0001511	99.91	gold quality
skin of abdomen	UBERON:0001416	99.90	gold quality
skeletal muscle tissue	UBERON:0001134	99.89	gold quality
colonic epithelium	UBERON:0000397	99.87	gold quality
ascending aorta	UBERON:0001496	99.87	gold quality
thoracic aorta	UBERON:0001515	99.87	gold quality
gastrocnemius	UBERON:0001388	99.86	gold quality
right ovary	UBERON:0002118	99.86	gold quality
descending thoracic aorta	UBERON:0002345	99.86	gold quality
middle frontal gyrus	UBERON:0002702	99.86	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.86	gold quality
ovary	UBERON:0000992	99.85	gold quality
muscle of leg	UBERON:0001383	99.85	gold quality
left coronary artery	UBERON:0001626	99.85	gold quality
apex of heart	UBERON:0002098	99.85	gold quality
left ovary	UBERON:0002119	99.85	gold quality
popliteal artery	UBERON:0002250	99.85	gold quality
bone marrow	UBERON:0002371	99.85	gold quality
tibial artery	UBERON:0007610	99.85	gold quality
granulocyte	CL:0000094	99.84	gold quality

Single-cell (SCXA)

Detected in 42 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	14281.61
E-MTAB-9221	yes	9768.16
E-MTAB-11268	yes	7298.46
E-GEOD-137537	yes	6195.67
E-HCAD-35	yes	2694.16
E-HCAD-31	yes	30.02
E-MTAB-9543	yes	14.36
E-MTAB-6678	yes	4.67
E-MTAB-8142	no	26152.78
E-MTAB-8884	no	23226.35
E-CURD-112	no	21822.68
E-CURD-46	no	20158.54
E-HCAD-4	no	18817.07
E-GEOD-130148	no	18051.40
E-HCAD-15	no	16473.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 14)

• the P1 and P2 proteins are not actively transported into the nucleus compartment, remaining predominantly in the cytoplasm (the perinuclear compartment). (PMID:12479870)
• Data indicate that P1/P2 proteins modulate cytoplasmic translation by influencing the interaction between subunits, thereby regulating the rate of cell proliferation. (PMID:18422483)
• These results support the hypothesis that at least some of the changes in the profile of newly synthesized proteins detected in cells deprived of P1 and P2 proteins might be due to an effect on the efficiency of cap-independent translation. (PMID:18675807)
• P proteins are up-regulated in a considerable number of patients with the most common types of cancer. (PMID:21040949)
• Data show that ricin A-chain (RTA) interacts directly with recombinant P1-P2 dimer, indicating the importance of P1 and P2 in enabling RTA to bind and depurinate ribosomes. (PMID:22909382)
• Evaluated autoantibodies against native ribosomal P complex and recombinant ribosomal P proteins (anti-Rib-P0, anti-Rib-P1, anti-Rib-P2) for prevalence, diagnostic relevance&clinical associations in a Chinese cohort with systemic lupus erythematosus. (PMID:23400861)
• absence of RPLP0, RPLP1, or RPLP2 resulted in reactive oxygen species (ROS) accumulation and MAPK1/ERK2 signaling pathway activation. (PMID:26176264)
• 60S acidic ribosomal protein P1 (RPLP1) is elevated in human endometriotic tissue and in a murine model of endometriosis and is essential for endometriotic epithelial cell survival in vitro. (PMID:31899515)
• CNN3 acts as a potential oncogene in cervical cancer by affecting RPLP1 mRNA expression. (PMID:32051425)
• Ribosomal stalk proteins RPLP1 and RPLP2 promote biogenesis of flaviviral and cellular multi-pass transmembrane proteins. (PMID:32890404)
• Phosphorylation of the conserved C-terminal domain of ribosomal P-proteins impairs the mode of interaction with plant toxins. (PMID:34328639)
• RPLP1 Is Up-Regulated in Human Adenomyosis and Endometrial Adenocarcinoma Epithelial Cells and Is Essential for Cell Survival and Migration In Vitro. (PMID:36769010)
• RPLP1 restricts HIV-1 transcription by disrupting C/EBPbeta binding to the LTR. (PMID:38906865)
• Esrra regulates Rplp1-mediated translation of lysosome proteins suppressed in metabolic dysfunction-associated steatohepatitis and reversed by alternate day fasting. (PMID:39032642)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rplp1	ENSDARG00000021864
mus_musculus	Rplp1	ENSMUSG00000007892
mus_musculus	Rplp1rt	ENSMUSG00000091014
rattus_norvegicus		ENSRNOG00000089334
drosophila_melanogaster	RpLP1	FBGN0002593
caenorhabditis_elegans	rla-1	WBGENE00004409

Paralogs (2): RPLP0 (ENSG00000089157), RPLP2 (ENSG00000177600)

Protein

Protein identifiers

Large ribosomal subunit protein P1 — P05386 (reviewed: P05386)

Alternative names: 60S acidic ribosomal protein P1

All UniProt accessions (2): P05386, H0YL57

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the elongation step of protein synthesis.

Subunit / interactions. Heterodimer with RPLP2 at the lateral ribosomal stalk of the large ribosomal subunit.

Post-translational modifications. Ubiquitinated at Lys-92 and Lys-93 by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling).

Similarity. Belongs to the eukaryotic ribosomal protein P1/P2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P05386-1	1	yes
P05386-2	2

RefSeq proteins (2): NP_000994, NP_998890 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027534	Ribosomal_P1/P2	Family
IPR038716	P1/P2_N_sf	Homologous_superfamily

Pfam: PF00428

UniProt features (16 total): helix 4, turn 2, compositionally biased region 2, modified residue 2, cross-link 2, initiator methionine 1, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4V6X	ELECTRON MICROSCOPY	5
2LBF	SOLUTION NMR
4BEH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05386-F1	70.93	0.30

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 (4): 2, 101, 92, 93

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: 239 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, MYOGENIN_Q6, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_151, GNF2_TPT1, MATTIOLI_MGUS_VS_PCL, MODULE_150, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, GOMF_KINASE_ACTIVATOR_ACTIVITY, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT

GO Biological Process (3): cytoplasmic translation (GO:0002181), translation (GO:0006412), translational elongation (GO:0006414)

GO Molecular Function (4): structural constituent of ribosome (GO:0003735), protein kinase activator activity (GO:0030295), ribonucleoprotein complex binding (GO:0043021), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), 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
translation	2
macromolecule biosynthetic process	2
ribosome	2
cellular anatomical structure	2
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
protein metabolic process	1
protein biosynthetic process	1
structural molecule activity	1
protein kinase activity	1
kinase activator activity	1
protein kinase regulator activity	1
protein-containing complex binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

2852 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPLP1	RPLP0	P05388	957
RPLP1	RPLP2	P05387	942
RPLP1	POP5	Q969H6	779
RPLP1	RPL12	P30050	729
RPLP1	RPL9	P32969	729
RPLP1	RPL4	P36578	727
RPLP1	RPS28	P25112	718
RPLP1	RPS25	P25111	710
RPLP1	RPL30	P04645	690
RPLP1	RPL10A	P52859	682
RPLP1	RPS24	P16632	681
RPLP1	RPS13	P19116	666
RPLP1	PARN	O95453	665
RPLP1	POP7	O75817	660
RPLP1	RPL13A	P40429	651

IntAct

234 interactions, top by confidence:

A	B	Type	Score
IFIT1	IFIT3	psi-mi:“MI:0914”(association)	0.920
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
CSNK2A1	RPLP1	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
RPLP1	RPLP2	psi-mi:“MI:0407”(direct interaction)	0.560
RPLP0	RPLP1	psi-mi:“MI:0915”(physical association)	0.560
RPLP1	SUOX	psi-mi:“MI:0915”(physical association)	0.560
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPL13	RPLP1	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PPP2R2B	DDX3X	psi-mi:“MI:0914”(association)	0.460
ACTB	DDX3X	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (411): RPLP1 (Affinity Capture-MS), RPLP1 (Affinity Capture-MS), RPLP1 (Affinity Capture-MS), RPL10A (Co-fractionation), RPL12 (Co-fractionation), RPL14 (Co-fractionation), RPL18 (Co-fractionation), RPL27A (Co-fractionation), RPL29 (Co-fractionation), RPL30 (Co-fractionation), RPL37A (Co-fractionation), RPL4 (Co-fractionation), RPL7A (Co-fractionation), RPLP1 (Co-fractionation), RPLP1 (Co-fractionation)

ESM2 similar proteins: A1XQU7, H2E5X2, O00806, O01359, O23095, O24415, O44010, O46313, O61463, P02402, P05318, P05386, P08570, P10622, P17476, P17477, P18660, P19944, P22684, P23632, P24002, P26643, P27055, P27464, P29763, P41099, P47955, P49148, P50344, P50879, P51407, P51408, P52855, P90703, P91913, Q06382, Q06383, Q49KL9, Q56K14, Q8LCW9

Diamond homologs: A1XQU7, H2E5X2, O01359, O23095, P02402, P05318, P05386, P08570, P17476, P17477, P18660, P19944, P22684, P26643, P27464, P29763, P47955, P49148, P50344, P52855, P91913, Q49KL9, Q56K14, Q8LCW9, Q8LEQ0, Q9HFQ6, Q9HFQ7, Q9HGV0, Q9UU78, O46313, P10622, P05768, P15772, P41197, P54048, O52706

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPLP1	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 216 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
SRP-dependent cotranslational protein targeting to membrane	21	13.3×	3e-15
Eukaryotic Translation Termination	16	12.2×	4e-11
Peptide chain elongation	15	12.1×	8e-11
Viral mRNA Translation	15	12.1×	8e-11
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	16	11.9×	4e-11
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	15	11.9×	9e-11
GTP hydrolysis and joining of the 60S ribosomal subunit	18	11.4×	6e-12
Selenocysteine synthesis	15	11.4×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	6	23.4×	4e-05
cytoplasmic translation	18	17.0×	2e-14
ribosomal large subunit biogenesis	7	15.8×	5e-05
stress granule assembly	5	15.3×	2e-03
negative regulation of translation	13	13.0×	8e-09
intrinsic apoptotic signaling pathway	6	11.0×	2e-03
mitophagy	6	9.7×	4e-03
translation	18	9.4×	4e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

376 predictions. Top by Δscore:

Variant	Effect	Δscore
15:69453021:G:GG	donor_gain	1.0000
15:69453022:T:A	donor_loss	1.0000
15:69453023:GAGT:G	donor_loss	1.0000
15:69453720:AGGT:A	donor_loss	1.0000
15:69453722:G:A	donor_loss	1.0000
15:69453723:T:G	donor_loss	1.0000
15:69455165:TGCA:T	acceptor_loss	1.0000
15:69455167:CAGG:C	acceptor_loss	1.0000
15:69455168:A:AC	acceptor_loss	1.0000
15:69455255:G:GT	donor_gain	1.0000
15:69455283:TCCAG:T	donor_loss	1.0000
15:69455284:CCAG:C	donor_loss	1.0000
15:69455285:CAGGT:C	donor_loss	1.0000
15:69455286:AGG:A	donor_loss	1.0000
15:69455289:T:G	donor_loss	1.0000
15:69455424:CTAGC:C	acceptor_loss	1.0000
15:69455425:TAGCT:T	acceptor_loss	1.0000
15:69455426:A:AG	acceptor_gain	1.0000
15:69455427:G:GG	acceptor_gain	1.0000
15:69455427:GC:G	acceptor_gain	1.0000
15:69455427:GCT:G	acceptor_gain	1.0000
15:69455427:GCTGA:G	acceptor_gain	1.0000
15:69453016:TCACG:T	donor_gain	0.9900
15:69453019:CG:C	donor_gain	0.9900
15:69453020:GG:G	donor_gain	0.9900
15:69453641:TTGTA:T	acceptor_loss	0.9900
15:69453642:TGTA:T	acceptor_loss	0.9900
15:69453643:GTAG:G	acceptor_loss	0.9900
15:69453644:TAGGA:T	acceptor_loss	0.9900
15:69453645:A:C	acceptor_loss	0.9900

AlphaMissense

739 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:69452975:C:G	C9W	0.999
15:69452986:C:A	A13D	0.999
15:69452989:T:C	L14P	0.999
15:69453677:G:C	A35P	0.999
15:69453678:C:A	A35D	0.999
15:69455497:T:A	L112H	0.999
15:69455499:T:C	F113L	0.999
15:69455501:T:A	F113L	0.999
15:69455501:T:G	F113L	0.999
15:69452973:T:C	C9R	0.998
15:69452974:G:A	C9Y	0.998
15:69452983:C:G	S12W	0.998
15:69452985:G:C	A13P	0.998
15:69452989:T:A	L14H	0.998
15:69452995:T:C	L16P	0.998
15:69453666:T:C	L31P	0.998
15:69453674:G:C	A34P	0.998
15:69453713:T:C	F47L	0.998
15:69453715:T:A	F47L	0.998
15:69453715:T:G	F47L	0.998
15:69455170:G:C	A50P	0.998
15:69455499:T:A	F113I	0.998
15:69452968:T:C	L7P	0.997
15:69452971:C:A	A8D	0.997
15:69452995:T:A	L16Q	0.997
15:69453016:T:A	V23D	0.997
15:69453666:T:A	L31H	0.997
15:69453701:T:A	W43R	0.997
15:69453701:T:C	W43R	0.997
15:69453716:G:C	A48P	0.997

dbSNP variants (sampled 300 via entrez): RS1001160155 (15:69456314 A>G), RS1001881437 (15:69456567 G>C), RS1001925283 (15:69451228 C>A,T), RS1002090835 (15:69451195 A>C), RS1002587722 (15:69453323 G>A,C), RS1002810961 (15:69453347 G>T), RS1002950809 (15:69453127 G>A,C), RS1003169298 (15:69453172 C>G,T), RS1003937286 (15:69451028 T>A), RS1004219083 (15:69452633 T>C,G), RS1004883858 (15:69455482 A>C), RS1005601074 (15:69453992 G>A,C), RS1005615434 (15:69452432 G>C), RS1005667521 (15:69452661 C>A,T), RS1005751556 (15:69454175 T>C)

Disease associations

OMIM: gene MIM:180520 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002073_20	Chronic lymphocytic leukemia	1.000000e-17
GCST002299_18	Chronic lymphocytic leukemia	8.000000e-18
GCST003810_5	Non-response to citalopram or escitalopram and depression	1.000000e-06
GCST003983_31	Male-pattern baldness	1.000000e-09
GCST004146_19	Chronic lymphocytic leukemia	2.000000e-31

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066978 (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 53 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.90	Kd	12.52	nM	CHEMBL3752910
7.90	ED50	12.52	nM	CHEMBL3752910
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
5.51	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 209 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149278: Binding affinity to human RPLP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0125	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
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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression, decreases expression	5
sodium arsenite	increases expression	2
Tobacco Smoke Pollution	increases methylation, affects expression	2
Valproic Acid	affects cotreatment, increases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
decabromobiphenyl ether	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
gossypol acetic acid	increases expression	1
cupric oxide	increases expression	1
CD 437	decreases expression	1
chloropicrin	affects 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
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Benztropine	affects cotreatment, decreases expression	1
Cisplatin	decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Disulfiram	increases expression	1

ChEMBL screening assays

90 unique, capped per target: 90 binding

Representative assays (with source publication via chembl_document):

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

Clinical trials (associated diseases)

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