RPL39

Summary

RPL39 (ribosomal protein L39, HGNC:10350) is a protein-coding gene on chromosome Xq24, encoding Large ribosomal subunit protein eL39 (P62891). RNA-binding component of the large ribosomal subunit. It is a selective cancer dependency (DepMap: 84.8% of 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 S39E family of ribosomal proteins. It is located in the cytoplasm. In rat, the protein is the smallest, and one of the most basic, proteins of the ribosome. This gene is co-transcribed with the U69 small nucleolar RNA gene, which is located in its second intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6170 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 11 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 84.8% of screened cell lines
• MANE Select transcript: NM_001000

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10350
Approved symbol	RPL39
Name	ribosomal protein L39
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	L39, eL39
Ensembl gene	ENSG00000198918
Ensembl biotype	protein_coding
OMIM	300899
Entrez	6170

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000361575, ENST00000468844, ENST00000477403, ENST00000931583, ENST00000949343

RefSeq mRNA: 1 — MANE Select: NM_001000 NM_001000

CCDS: CCDS14586

Canonical transcript exons

ENST00000361575 — 3 exons

Exon	Start	End
ENSE00001434762	119789908	119790011
ENSE00001436322	119791574	119791630
ENSE00003631287	119786504	119786732

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 83.8462 / max 830.1444, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200306	62.1089	1811
200307	20.5281	1791
200305	1.2092	708

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.97	gold quality
endometrium	UBERON:0001295	99.94	gold quality
ventricular zone	UBERON:0003053	99.94	gold quality
cortical plate	UBERON:0005343	99.94	gold quality
granulocyte	CL:0000094	99.93	gold quality
left ovary	UBERON:0002119	99.92	gold quality
zone of skin	UBERON:0000014	99.91	gold quality
ovary	UBERON:0000992	99.91	gold quality
skin of abdomen	UBERON:0001416	99.91	gold quality
skin of leg	UBERON:0001511	99.91	gold quality
right ovary	UBERON:0002118	99.91	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.91	gold quality
thoracic mammary gland	UBERON:0005200	99.91	gold quality
lymph node	UBERON:0000029	99.90	gold quality
adipose tissue	UBERON:0001013	99.90	gold quality
spleen	UBERON:0002106	99.90	gold quality
omental fat pad	UBERON:0010414	99.90	gold quality
rectum	UBERON:0001052	99.89	gold quality
right adrenal gland	UBERON:0001233	99.89	gold quality
right adrenal gland cortex	UBERON:0035827	99.89	gold quality
leukocyte	CL:0000738	99.88	gold quality
endocervix	UBERON:0000458	99.88	gold quality
vagina	UBERON:0000996	99.88	gold quality
vermiform appendix	UBERON:0001154	99.88	gold quality
right uterine tube	UBERON:0001302	99.88	gold quality
fallopian tube	UBERON:0003889	99.88	gold quality
mucosa of transverse colon	UBERON:0004991	99.88	gold quality
ectocervix	UBERON:0012249	99.88	gold quality
left adrenal gland cortex	UBERON:0035825	99.88	gold quality
monocyte	CL:0000576	99.87	gold quality

Single-cell (SCXA)

Detected in 50 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	12337.68
E-CURD-122	yes	9268.10
E-GEOD-134144	yes	8570.23
E-MTAB-9221	yes	7555.19
E-GEOD-124263	yes	7142.20
E-MTAB-7316	yes	5278.38
E-CURD-88	yes	73.06
E-MTAB-9067	yes	29.11
E-GEOD-135922	yes	26.39
E-GEOD-137537	yes	6.17
E-HCAD-35	yes	4.73
E-HCAD-31	yes	4.16
E-MTAB-10432	no	22478.68
E-CURD-55	no	13769.11
E-HCAD-6	no	13081.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting RPL39, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529
HSA-MIR-5189-3P	97.52	66.33	487

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 84.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• Small interfering RNA (siRNA) targeting of the RPL39 gene was done to determine the effects of the RPL39 gene on growth of pancreatic cancer PANC-1 and BxPC-3 cells in vitro and in vivo. (PMID:24799381)
• RPL39 and MLF2 have roles in tumor initiation and metastasis in breast cancer that involve nitric oxide synthase signaling (PMID:24876273)
• RPL39 mediated its cancer-promoting actions through iNOS signaling, which was driven by the RNA editing enzyme adenosine deaminase acting on RNA 1. (PMID:28040796)
• Acylglycerol kinase promotes ovarian cancer progression and regulates mitochondria function by interacting with ribosomal protein L39. (PMID:35934718)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl39	ENSDARG00000036316
mus_musculus	Rpl39	ENSMUSG00000079641
rattus_norvegicus	Rpl39	ENSRNOG00000043348

Paralogs (1): RPL39L (ENSG00000163923)

Protein

Protein identifiers

Large ribosomal subunit protein eL39 — P62891 (reviewed: P62891)

Alternative names: 60S ribosomal protein L39

All UniProt accessions (1): P62891

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding 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. Interacts with IMPACT.

Subcellular location. Cytoplasm.

Similarity. Belongs to the eukaryotic ribosomal protein eL39 family.

RefSeq proteins (1): NP_000991* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000077	Ribosomal_eL39	Family
IPR020083	Ribosomal_eL39_CS	Conserved_site
IPR023626	Ribosomal_eL39_dom_sf	Homologous_superfamily

Pfam: PF00832

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

181 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
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
8JDJ	ELECTRON MICROSCOPY	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62891-F1	94.22	0.93

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: 209 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, MODULE_151, GNF2_TPT1, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT

GO Biological Process (7): cytoplasmic translation (GO:0002181), innate immune response in mucosa (GO:0002227), translation (GO:0006412), antibacterial humoral response (GO:0019731), defense response to Gram-positive bacterium (GO:0050830), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), RNA processing (GO:0006396)

GO Molecular Function (2): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), cytosol (GO:0005829), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), nucleolus (GO:0005730), cytoplasm (GO:0005737), 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
antimicrobial humoral response	2
defense response to bacterium	2
ribosome	2
cellular anatomical structure	2
intracellular membraneless organelle	2
translation	1
mucosal immune response	1
innate immune response	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
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
nucleic acid binding	1
structural molecule activity	1
cytoplasm	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
nuclear lumen	1
intracellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

51 interactions, top by confidence:

A	B	Type	Score
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
AEBP2	EED	psi-mi:“MI:0914”(association)	0.650
LCOR	PHF1	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPS6	IPO7	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
RBBP7	EPOP	psi-mi:“MI:0914”(association)	0.530
RPL39	LRRK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
GSK3B	SEC16A	psi-mi:“MI:0914”(association)	0.420
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
RPL39	E6	psi-mi:“MI:0915”(physical association)	0.370
S100A9	RPL39	psi-mi:“MI:0915”(physical association)	0.370
EBNA1	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
BCAR1	PSMD11	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
C9orf72	CHD2	psi-mi:“MI:0914”(association)	0.350
IRF2	VWA8	psi-mi:“MI:0914”(association)	0.350
OAS3	PTBP1	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
VMP1	TPM3	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
SOCS1	NDUFA4	psi-mi:“MI:0914”(association)	0.350
DUSP6	HSPA8	psi-mi:“MI:0914”(association)	0.350
GRB7	RIOK3	psi-mi:“MI:0914”(association)	0.350
CAMK2A	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
PTPN6	RPL35A	psi-mi:“MI:0914”(association)	0.350
AXL	DNAJA2	psi-mi:“MI:0914”(association)	0.350
TAGLN	LOC392647	psi-mi:“MI:0914”(association)	0.350

BioGRID (129): RPL39 (Affinity Capture-MS), RPL39 (Affinity Capture-MS), RPL37A (Co-fractionation), RPL39 (Co-fractionation), RPL39 (Co-fractionation), RPL39 (Co-fractionation), RPL39 (Co-fractionation), RPL39 (Co-fractionation), RPL39 (Co-fractionation), RPL39 (Co-fractionation), RPL39 (Co-fractionation), RPL39 (Co-fractionation), RPS15 (Co-fractionation), RPS18 (Co-fractionation), RPS3A (Co-fractionation)

ESM2 similar proteins: A0A1D8PDT4, A2STI9, A4G029, A6VIE9, A9A8D5, B0R7X9, C0H3Z0, C5A7H4, C6A264, G1SYU7, O16130, O74175, P04538, P04650, P05767, P11340, P22452, P51424, P51425, P51426, P52814, P54573, P62891, P62892, P62893, Q05293, Q18EU6, Q24154, Q37928, Q3T051, Q59GN2, Q5JGT6, Q5SMI4, Q6BHV8, Q6CW22, Q6F482, Q6KAJ8, Q6M0V9, Q758D8, Q8L8W6

Diamond homologs: A0A1D8PDT4, A2BN55, A2STI9, A3CWZ6, A3DNH3, A4G029, A4YH79, A5UL33, A6URE0, A6UVQ6, A6VIE9, A8MAL5, A9A8D5, B0R7X9, B6YWY4, B8GEU4, B9LUV0, C3MR76, C3MXG5, C3MZB1, C3N7D1, C3NGA3, C4KII9, C5A7H4, C6A264, G1SYU7, O16130, O27650, O28212, P04650, P05767, P0DJ61, P13005, P22452, P48536, P51424, P51425, P51426, P52814, P54056

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL39	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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
PRC2 methylates histones and DNA	6	15.0×	1e-03
PKMTs methylate histone lysines	5	13.2×	9e-03
Major pathway of rRNA processing in the nucleolus and cytosol	7	7.1×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	5	13.2×	7e-03
rRNA processing	6	12.1×	4e-03
chromatin organization	7	9.9×	4e-03
translation	6	8.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
442001	GRCh37/hg19 Xq21.1-28(chrX:79862302-155233731)x1	Pathogenic

SpliceAI

373 predictions. Top by Δscore:

Variant	Effect	Δscore
X:119786730:TACC:T	acceptor_loss	1.0000
X:119786736:C:CT	acceptor_gain	1.0000
X:119789904:TTAC:T	donor_loss	1.0000
X:119789905:TA:T	donor_loss	1.0000
X:119789906:A:AC	donor_gain	1.0000
X:119789907:C:A	donor_loss	1.0000
X:119789907:C:CC	donor_gain	1.0000
X:119789907:CCTG:C	donor_gain	1.0000
X:119789907:CCTGA:C	donor_gain	1.0000
X:119790007:GAAGA:G	acceptor_gain	1.0000
X:119790008:AAGA:A	acceptor_gain	1.0000
X:119790009:AGA:A	acceptor_gain	1.0000
X:119790010:GA:G	acceptor_gain	1.0000
X:119790012:C:CC	acceptor_gain	1.0000
X:119790023:A:C	acceptor_gain	1.0000
X:119791571:TACCA:T	donor_loss	1.0000
X:119791572:A:AC	donor_gain	1.0000
X:119791573:C:CC	donor_gain	1.0000
X:119786728:TGTAC:T	acceptor_gain	0.9900
X:119786729:GTAC:G	acceptor_gain	0.9900
X:119786730:TAC:T	acceptor_gain	0.9900
X:119786731:AC:A	acceptor_gain	0.9900
X:119786732:CC:C	acceptor_gain	0.9900
X:119786733:C:CC	acceptor_gain	0.9900
X:119789906:AC:A	donor_gain	0.9900
X:119789907:CC:C	donor_gain	0.9900
X:119789907:CCT:C	donor_gain	0.9900
X:119790023:A:AC	acceptor_gain	0.9900
X:119791572:AC:A	donor_gain	0.9900
X:119791573:CC:C	donor_gain	0.9900

AlphaMissense

331 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:119789939:A:G	W26R	0.997
X:119789939:A:T	W26R	0.997
X:119786710:A:G	W44R	0.995
X:119786710:A:T	W44R	0.995
X:119786708:C:A	W44C	0.991
X:119786708:C:G	W44C	0.991
X:119786717:C:A	R41S	0.991
X:119786717:C:G	R41S	0.991
X:119786714:T:A	R42S	0.990
X:119786714:T:G	R42S	0.990
X:119789938:C:G	W26S	0.989
X:119786705:T:A	R45S	0.988
X:119786705:T:G	R45S	0.988
X:119789937:C:A	W26C	0.988
X:119789937:C:G	W26C	0.988
X:119789938:C:A	W26L	0.987
X:119786715:C:G	R42T	0.986
X:119786718:C:G	R41T	0.986
X:119786709:C:G	W44S	0.984
X:119786718:C:A	R41M	0.984
X:119789985:C:A	K10N	0.984
X:119789985:C:G	K10N	0.984
X:119786706:C:G	R45T	0.982
X:119786726:G:C	N38K	0.982
X:119786726:G:T	N38K	0.982
X:119789955:A:C	N20K	0.982
X:119789955:A:T	N20K	0.982
X:119786715:C:A	R42I	0.981
X:119786709:C:A	W44L	0.980
X:119789953:C:G	R21P	0.980

dbSNP variants (sampled 300 via entrez): RS1000190599 (X:119792176 C>T), RS1000635674 (X:119786515 G>A), RS1001146601 (X:119787285 C>A), RS1001330920 (X:119790299 G>A), RS1001440055 (X:119786903 A>T), RS1001595551 (X:119790572 T>C), RS1002043160 (X:119789349 G>A), RS1002541445 (X:119790038 A>G), RS1003138935 (X:119791811 G>GT), RS1003434025 (X:119791604 A>C,T), RS1003530601 (X:119788707 C>T), RS1003667878 (X:119788352 T>G), RS1004057894 (X:119792663 C>T), RS1004146296 (X:119788914 C>T), RS1004534887 (X:119786977 C>T)

Disease associations

OMIM: gene MIM:300899 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_391	Metabolite levels	7.000000e-06
GCST011999_14	Hepatitis C (spontaneous viral clearance)	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010437	triacylglycerol 58:10 measurement
EFO:0009785	remission

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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, affects expression	4
Air Pollutants	affects expression, increases abundance, decreases expression	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
Cadmium Chloride	increases expression, decreases reaction, increases abundance, increases palmitoylation	2
bisphenol F	affects cotreatment, decreases methylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases expression	1
arsenite	increases reaction, affects binding	1
methylparaben	decreases expression	1
sodium arsenite	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
phenanthrene	decreases expression	1
perfluorodecanoic acid	decreases expression	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Cisplatin	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Ozone	affects expression, increases abundance	1
Rotenone	decreases expression	1
Selenium	decreases expression	1
Smoke	decreases expression, increases abundance	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.