RPLP0

Summary

RPLP0 (ribosomal protein lateral stalk subunit P0, HGNC:10371) is a protein-coding gene on chromosome 12q24.23, encoding Large ribosomal subunit protein uL10 (P05388). Ribosomal protein P0 is the functional equivalent of E.coli protein L10. 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 protein that is a component of the 60S subunit. The protein, which is the functional equivalent of the E. coli L10 ribosomal protein, belongs to the L10P family of ribosomal proteins. It is a neutral phosphoprotein with a C-terminal end that is nearly identical to the C-terminal ends of the acidic ribosomal phosphoproteins P1 and P2. The P0 protein can interact with P1 and P2 to form a pentameric complex consisting of P1 and P2 dimers, and a P0 monomer. The protein is located in the cytoplasm. Transcript variants derived from alternative splicing exist; they encode the same protein. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6175 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 50 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_001002

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10371
Approved symbol	RPLP0
Name	ribosomal protein lateral stalk subunit P0
Location	12q24.23
Locus type	gene with protein product
Status	Approved
Aliases	PRLP0, P0, L10E, RPP0, LP0, uL10
Ensembl gene	ENSG00000089157
Ensembl biotype	protein_coding
OMIM	180510
Entrez	6175

Gene structure

Transcript identifiers

Ensembl transcripts: 61 — 46 protein_coding, 9 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000228306, ENST00000313104, ENST00000392514, ENST00000546564, ENST00000546989, ENST00000546990, ENST00000547173, ENST00000547191, ENST00000547211, ENST00000547475, ENST00000548495, ENST00000548551, ENST00000548568, ENST00000549098, ENST00000549242, ENST00000550296, ENST00000550423, ENST00000550856, ENST00000551150, ENST00000551217, ENST00000551258, ENST00000551336, ENST00000551783, ENST00000551914, ENST00000552292, ENST00000552461, ENST00000552902, ENST00000874747, ENST00000874748, ENST00000874749, ENST00000874750, ENST00000874751, ENST00000874752, ENST00000874753, ENST00000874754, ENST00000874755, ENST00000874756, ENST00000926179, ENST00000926180, ENST00000926181, ENST00000926182, ENST00000926183, ENST00000926184, ENST00000926185, ENST00000926186, ENST00000926187, ENST00000926188, ENST00000926189, ENST00000926190, ENST00000926191, ENST00000926192, ENST00000926193, ENST00000926194, ENST00000926195, ENST00000926196, ENST00000926197, ENST00000926198, ENST00000971888, ENST00000971889, ENST00000971890, ENST00000971891

RefSeq mRNA: 2 — MANE Select: NM_001002 NM_001002, NM_053275

CCDS: CCDS9193

Canonical transcript exons

ENST00000392514 — 8 exons

Exon	Start	End
ENSE00002395648	120196699	120196934
ENSE00003535345	120198854	120199000
ENSE00003594111	120198554	120198739
ENSE00003622096	120200730	120200831
ENSE00003627262	120199310	120199485
ENSE00003654998	120199118	120199205
ENSE00003787847	120197322	120197462
ENSE00003844202	120201083	120201111

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 99.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 304.8240 / max 4965.8294, expressed in 1825 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133597	304.8240	1825

Top tissues by expression

160 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	99.98	gold quality
stromal cell of endometrium	CL:0002255	99.93	gold quality
ventricular zone	UBERON:0003053	99.92	gold quality
skin of leg	UBERON:0001511	99.89	gold quality
esophagus mucosa	UBERON:0002469	99.89	gold quality
islet of Langerhans	UBERON:0000006	99.88	gold quality
zone of skin	UBERON:0000014	99.88	gold quality
right uterine tube	UBERON:0001302	99.88	gold quality
ganglionic eminence	UBERON:0004023	99.88	gold quality
embryo	UBERON:0000922	99.87	gold quality
body of pancreas	UBERON:0001150	99.87	gold quality
pancreas	UBERON:0001264	99.87	gold quality
skin of abdomen	UBERON:0001416	99.87	gold quality
right ovary	UBERON:0002118	99.87	gold quality
fallopian tube	UBERON:0003889	99.87	gold quality
ovary	UBERON:0000992	99.86	gold quality
rectum	UBERON:0001052	99.86	gold quality
smooth muscle tissue	UBERON:0001135	99.86	gold quality
body of stomach	UBERON:0001161	99.86	gold quality
left ovary	UBERON:0002119	99.86	gold quality
lower esophagus mucosa	UBERON:0035834	99.86	gold quality
vagina	UBERON:0000996	99.85	gold quality
esophagus	UBERON:0001043	99.85	gold quality
fundus of stomach	UBERON:0001160	99.85	gold quality
mucosa of stomach	UBERON:0001199	99.85	gold quality
right adrenal gland	UBERON:0001233	99.85	gold quality
left adrenal gland	UBERON:0001234	99.85	gold quality
minor salivary gland	UBERON:0001830	99.85	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.85	gold quality
left adrenal gland cortex	UBERON:0035825	99.85	gold quality

Single-cell (SCXA)

Detected in 47 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	10501.16
E-MTAB-10042	yes	6573.90
E-MTAB-9801	yes	5241.17
E-GEOD-149689	yes	5203.34
E-MTAB-6308	yes	4309.68
E-HCAD-13	yes	4152.59
E-CURD-122	yes	85.39
E-HCAD-11	yes	54.38
E-MTAB-9221	yes	51.75
E-CURD-46	yes	37.66
E-HCAD-9	yes	17.07
E-MTAB-9543	yes	13.06
E-HCAD-35	yes	8.84
E-CURD-84	no	7696.82
E-MTAB-8205	no	6811.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EZH2

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 14)

• The P0 protein was found in the cytoplasm, as well as in the nucleus; however, the nucleoli were excluded. This protein was scattered around the nuclei, and the distribution might reflect association with the so-called nuclear bodies (PMID:12479870)
• Recombinant fusion protein GST.P0 expressed in insect cells, but not the protein obtained in Escherichia coli, had the ability to form a complex with P1 and P2 proteins. (PMID:15336536)
• P0 overexpression may cause tumorigenesis in breast and liver tissues at least in part by inhibiting GCIP-mediated tumor suppression. (PMID:17621266)
• Results show that RPL4, RPLP0, and HSPCB were the most stable reference genes in ovarian tissues. (PMID:20705598)
• P proteins are up-regulated in a considerable number of patients with the most common types of cancer. (PMID:21040949)
• 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)
• the immune response mediated by serum anti-RPLP0 and anti-galectin 3 antibodies plays a key role in the pathogenesis of SLE skin lesions. These findings provide new insights into the mechanism of SLE-related organ disorders. (PMID:25307291)
• Down-regulation of RPLP0 resulted in G1 arrest of gastric cancer cells (PMID:25433997)
• This study shows a spontaneous humoral immune response to ribosomal P0 protein in colorectal cancer patients. (PMID:25889931)
• absence of RPLP0, RPLP1, or RPLP2 resulted in reactive oxygen species (ROS) accumulation and MAPK1/ERK2 signaling pathway activation. (PMID:26176264)
• The presence of uL10 on the ribosomes is affected in stressed cells, thus it might be considered as a regulatory element responding to environmental fluctuations. (PMID:28986221)
• Phosphorylation of the N-terminal domain of ribosomal P-stalk protein uL10 governs its association with the ribosome. (PMID:32668052)
• DNA damage-induced paraspeckle formation enhances DNA repair and tumor radioresistance by recruiting ribosomal protein P0. (PMID:35974014)
• TNF-alpha and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema. (PMID:39110356)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rplp0	ENSDARG00000051783
drosophila_melanogaster	RpLP0	FBGN0000100
caenorhabditis_elegans	rla-0	WBGENE00004408

Paralogs (2): RPLP1 (ENSG00000137818), RPLP2 (ENSG00000177600)

Protein

Protein identifiers

Large ribosomal subunit protein uL10 — P05388 (reviewed: P05388)

Alternative names: 60S acidic ribosomal protein P0, 60S ribosomal protein L10E

All UniProt accessions (13): P05388, F8VPE8, F8VQY6, F8VRK7, F8VS58, F8VU65, F8VW21, F8VWS0, F8VWV4, F8VYN4, F8VZS0, F8W1K8, G3V210

UniProt curated annotations — full annotation on UniProt →

Function. Ribosomal protein P0 is the functional equivalent of E.coli protein L10.

Subunit / interactions. P0 forms a pentameric complex by interaction with dimers of P1 and P2. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with APEX1. Interacts with FMR1 isoform 6.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Ubiquitinated at Lys-264 by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling).

Similarity. Belongs to the universal ribosomal protein uL10 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P05388-1	1	yes
P05388-2	2

RefSeq proteins (2): NP_000993, NP_444505 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001790	Ribosomal_uL10_N	Domain
IPR030670	uL10_euk	Family
IPR040637	Ribosomal_uL10-like_insert	Domain
IPR043141	Ribosomal_uL10-like_sf	Homologous_superfamily
IPR043164	Ribosomal_uL10-like_insert_sf	Homologous_superfamily
IPR050323	Ribosomal_protein_uL10	Family

Pfam: PF00428, PF00466, PF17777

UniProt features (12 total): modified residue 4, cross-link 3, chain 1, region of interest 1, splice variant 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

81 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8YOO	ELECTRON MICROSCOPY	2
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8YOP	ELECTRON MICROSCOPY	2.2
9S3D	ELECTRON MICROSCOPY	2.32
9S3B	ELECTRON MICROSCOPY	2.38
8K2C	ELECTRON MICROSCOPY	2.4
8XSX	ELECTRON MICROSCOPY	2.4
9S3C	ELECTRON MICROSCOPY	2.42
9QLO	ELECTRON MICROSCOPY	2.47
9P8B	ELECTRON MICROSCOPY	2.48
8G60	ELECTRON MICROSCOPY	2.54
9P7D	ELECTRON MICROSCOPY	2.57
9QLQ	ELECTRON MICROSCOPY	2.57
9P7E	ELECTRON MICROSCOPY	2.59
6ZMI	ELECTRON MICROSCOPY	2.6
8G5Z	ELECTRON MICROSCOPY	2.64
9P7O	ELECTRON MICROSCOPY	2.65
9P73	ELECTRON MICROSCOPY	2.66
9PA7	ELECTRON MICROSCOPY	2.67
6ZM7	ELECTRON MICROSCOPY	2.7
9P7Y	ELECTRON MICROSCOPY	2.75
9QLP	ELECTRON MICROSCOPY	2.75
9P9I	ELECTRON MICROSCOPY	2.77
9P7C	ELECTRON MICROSCOPY	2.78
8G6J	ELECTRON MICROSCOPY	2.8
9P72	ELECTRON MICROSCOPY	2.8
9P7K	ELECTRON MICROSCOPY	2.8
9P7A	ELECTRON MICROSCOPY	2.81
9B0P	ELECTRON MICROSCOPY	2.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05388-F1	80.12	0.32

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): 24, 59, 304, 307, 264, 297, 297

Function

Pathways and Gene Ontology

Reactome pathways

17 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-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
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: 277 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_151, MODULE_150, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, GOBP_MALE_GAMETE_GENERATION, AAAYRNCTG_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, CCANNAGRKGGC_UNKNOWN, NKX62_Q2

GO Biological Process (3): cytoplasmic translation (GO:0002181), translation (GO:0006412), ribosome biogenesis (GO:0042254)

GO Molecular Function (4): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), large ribosomal subunit rRNA binding (GO:0070180), protein binding (GO:0005515)

GO Cellular Component (14): nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), focal adhesion (GO:0005925), postsynaptic density (GO:0014069), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), cytoplasmic ribonucleoprotein granule (GO:0036464), extracellular exosome (GO:0070062), postsynapse (GO:0098794), ribonucleoprotein complex (GO:1990904), ribosome (GO:0005840)

Reactome top-level categories

Rollup of top-12 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
Interleukin-12 signaling	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	4
cytoplasm	3
ribosome	2
intracellular membrane-bounded 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
ribonucleoprotein complex biogenesis	1
nucleic acid binding	1
structural molecule activity	1
rRNA binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
cell-substrate junction	1
asymmetric synapse	1
postsynaptic specialization	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
ribonucleoprotein granule	1
extracellular vesicle	1
synapse	1
protein-containing complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

6605 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPLP0	RPLP1	P05386	957
RPLP0	RPLP2	P05387	941
RPLP0	RPL4	P36578	869
RPLP0	POTEF	A5A3E0	829
RPLP0	RPL12	P30050	824
RPLP0	ACTB	P02570	812
RPLP0	GAPDH	P00354	753
RPLP0	RPL18	Q07020	740
RPLP0	RPS3	P23396	726
RPLP0	RPSA	P08865	725
RPLP0	RPL8	P25120	721
RPLP0	EEF2	P13639	721
RPLP0	RPS2	P15880	721
RPLP0	B2M	P01884	710
RPLP0	RPL3	P39023	707

IntAct

387 interactions, top by confidence:

A	B	Type	Score
CCNDBP1	RPLP0	psi-mi:“MI:0915”(physical association)	0.800
RPLP0	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.800
RPLP0	CCNDBP1	psi-mi:“MI:0914”(association)	0.800
STAU1	RPLP0	psi-mi:“MI:0914”(association)	0.750
RPLP0	STAU1	psi-mi:“MI:0915”(physical association)	0.750
NCK1	NCK2	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
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
ESR1	TRIM24	psi-mi:“MI:0914”(association)	0.640
DDX6	RPLP0	psi-mi:“MI:0915”(physical association)	0.620
RPLP0	RPLP1	psi-mi:“MI:0915”(physical association)	0.560
NOM1	RPLP0	psi-mi:“MI:0914”(association)	0.530
MAGEB10	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530

BioGRID (962): RPLP0 (Affinity Capture-MS), RPLP0 (Affinity Capture-MS), CCNDBP1 (Two-hybrid), RPLP0 (Affinity Capture-MS), RPLP0 (Affinity Capture-MS), RPLP0 (Affinity Capture-MS), RPLP0 (Affinity Capture-MS), RPLP0 (Affinity Capture-MS), CCNDBP1 (Affinity Capture-MS), TUBA8 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), RPLP0 (Affinity Capture-MS), DDX24 (Co-fractionation), EEF1A1 (Co-fractionation), EIF5B (Co-fractionation)

ESM2 similar proteins: A2YDY2, A5PK63, A8D8X1, A9CB60, B7NZQ2, G1SGX4, G1TG89, G1TU13, P02362, P04644, P05388, P08636, P08708, P14131, P14869, P19945, P27635, P42794, P42795, P46287, P50894, P62084, P62244, P62245, P62246, P62249, P62250, P63273, P63274, P63275, P63276, P86048, Q0DK10, Q29195, Q29201, Q2TBW8, Q3T0X6, Q4R7Y2, Q5R931, Q5R938

Diamond homologs: A3DNI2, A4FZS8, A5UKU8, A6UTF8, A6VIP9, A8ABQ7, A9A838, B0R4W1, B6YSX9, C3MR85, C3MXH4, C3MZC0, C3N7E1, C3NG93, C4KIJ9, C5A428, C6A1F5, O24573, O27717, O28781, O52705, O74109, O74864, P05388, P13553, P15825, P15826, P19889, P35023, P41198, P47826, P50345, P54049, P57692, P96039, Q12UP8, Q29214, Q2NEW2, Q3INI7, Q46EU9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPLP0	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 203 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	20	14.1×	5e-15
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	17	14.1×	9e-13
Eukaryotic Translation Termination	15	12.7×	6e-11
Peptide chain elongation	14	12.5×	3e-10
Viral mRNA Translation	14	12.5×	3e-10
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	18	12.4×	9e-13
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	14	12.4×	3e-10
Selenocysteine synthesis	14	11.8×	5e-10

GO biological processes:

GO term	Partners	Fold	FDR
stress granule assembly	6	19.8×	1e-04
cytoplasmic translation	17	17.3×	1e-13
amyloid fibril formation	5	16.5×	1e-03
mRNA stabilization	7	14.1×	1e-04
mitophagy	8	14.0×	3e-05
stem cell population maintenance	5	11.6×	5e-03
translational initiation	5	9.8×	9e-03
intrinsic apoptotic signaling pathway	5	9.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1053 predictions. Top by Δscore:

Variant	Effect	Δscore
12:120196930:TTGAC:T	acceptor_gain	1.0000
12:120196931:TGAC:T	acceptor_gain	1.0000
12:120196932:GAC:G	acceptor_gain	1.0000
12:120196933:AC:A	acceptor_gain	1.0000
12:120196934:CC:C	acceptor_gain	1.0000
12:120196935:C:CC	acceptor_gain	1.0000
12:120196935:C:CG	acceptor_loss	1.0000
12:120196935:C:T	acceptor_gain	1.0000
12:120197317:TTTA:T	donor_loss	1.0000
12:120197319:TACC:T	donor_loss	1.0000
12:120197320:A:AG	donor_loss	1.0000
12:120197321:C:A	donor_loss	1.0000
12:120197459:CACC:C	acceptor_gain	1.0000
12:120197461:CC:C	acceptor_gain	1.0000
12:120197462:CC:C	acceptor_gain	1.0000
12:120197463:C:CA	acceptor_loss	1.0000
12:120198555:T:TA	donor_gain	1.0000
12:120198579:T:A	donor_gain	1.0000
12:120198736:CACT:C	acceptor_gain	1.0000
12:120198738:CT:C	acceptor_gain	1.0000
12:120198740:C:CC	acceptor_gain	1.0000
12:120198746:C:CT	acceptor_gain	1.0000
12:120198897:AAAG:A	donor_gain	1.0000
12:120199001:CTGA:C	acceptor_loss	1.0000
12:120199002:T:G	acceptor_loss	1.0000
12:120199112:CCTTA:C	donor_loss	1.0000
12:120199113:CTTA:C	donor_loss	1.0000
12:120199114:TTA:T	donor_loss	1.0000
12:120199115:TA:T	donor_loss	1.0000
12:120199116:A:AC	donor_gain	1.0000

AlphaMissense

2072 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:120198656:G:C	F183L	1.000
12:120198656:G:T	F183L	1.000
12:120198658:A:G	F183L	1.000
12:120198672:A:G	L178P	1.000
12:120198681:A:G	L175P	1.000
12:120198684:A:G	L174P	1.000
12:120198684:A:T	L174Q	1.000
12:120198691:C:G	A172P	1.000
12:120198858:A:C	I154S	1.000
12:120198858:A:G	I154T	1.000
12:120198864:A:T	I152N	1.000
12:120198865:T:A	I152F	1.000
12:120198870:C:A	G150V	1.000
12:120198870:C:T	G150D	1.000
12:120198871:C:G	G150R	1.000
12:120198873:C:G	R149T	1.000
12:120198879:A:C	I147S	1.000
12:120198879:A:G	I147T	1.000
12:120198879:A:T	I147N	1.000
12:120198881:T:A	K146N	1.000
12:120198881:T:G	K146N	1.000
12:120198883:T:C	K146E	1.000
12:120198900:G:T	A140D	1.000
12:120198906:A:G	F138S	1.000
12:120198908:A:C	F137L	1.000
12:120198908:A:T	F137L	1.000
12:120198909:A:C	F137C	1.000
12:120198909:A:G	F137S	1.000
12:120198910:A:G	F137L	1.000
12:120198930:A:G	L130P	1.000

dbSNP variants (sampled 300 via entrez): RS1000661459 (12:120199074 G>A), RS1000683619 (12:120201039 T>C,G), RS1001291606 (12:120201891 G>A,T), RS1001389164 (12:120202087 C>G,T), RS1001529744 (12:120201481 C>G,T), RS1001687066 (12:120196610 A>C,T), RS1001892300 (12:120198373 A>G), RS1002448411 (12:120198199 C>A,T), RS1002745752 (12:120197716 A>G), RS1002900515 (12:120199894 G>A), RS1003200200 (12:120200683 T>C,G), RS1003794806 (12:120197980 G>A,C), RS1004310181 (12:120197873 A>G), RS1005469537 (12:120196673 A>T), RS1005619217 (12:120202440 T>A)

Disease associations

OMIM: gene MIM:180510 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008161_75	Waist circumference adjusted for body mass index	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX)

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

46 potent at pChembl≥5 of 50 total, top 45 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
5.51	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

46 with measured affinity, of 205 total; 26 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
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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, affects cotreatment	3
perfluorooctane sulfonic acid	increases expression, decreases expression	2
chloropicrin	affects expression, decreases expression	2
Arsenic Trioxide	decreases expression	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
9-hydroxyoctadecadienoic acid	increases expression	1
napabucasin	decreases expression	1
geldanamycin	decreases expression	1
sodium arsenate	decreases expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
3,3’-diindolylmethane	decreases expression, decreases reaction	1
sodium arsenite	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
bufalin	decreases expression	1
perfluorooctanoic acid	decreases expression	1
cupric oxide	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
tanespimycin	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
bisphenol B	increases expression	1
diphenylarsinic acid	increases expression	1

ChEMBL screening assays

89 unique, capped per target: 89 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.