RPL6

Summary

RPL6 (ribosomal protein L6, HGNC:10362) is a protein-coding gene on chromosome 12q24.13, encoding Large ribosomal subunit protein eL6 (Q02878). Component of the large ribosomal subunit. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes a protein component of the 60S ribosomal subunit. This protein can bind specifically to domain C of the tax-responsive enhancer element of human T-cell leukemia virus type 1, and may participate in tax-mediated transactivation of transcription. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6128 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 41 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_000970

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10362
Approved symbol	RPL6
Name	ribosomal protein L6
Location	12q24.13
Locus type	gene with protein product
Status	Approved
Aliases	TAXREB107, L6, eL6
Ensembl gene	ENSG00000089009
Ensembl biotype	protein_coding
OMIM	603703
Entrez	6128

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 32 protein_coding, 5 retained_intron

ENST00000202773, ENST00000424576, ENST00000546368, ENST00000548343, ENST00000549562, ENST00000549847, ENST00000550238, ENST00000550566, ENST00000551041, ENST00000551291, ENST00000552455, ENST00000553205, ENST00000553213, ENST00000895614, ENST00000895615, ENST00000895616, ENST00000895617, ENST00000895618, ENST00000895619, ENST00000895620, ENST00000935336, ENST00000935337, ENST00000935338, ENST00000935339, ENST00000935340, ENST00000935341, ENST00000935342, ENST00000935343, ENST00000935344, ENST00000935345, ENST00000935346, ENST00000935347, ENST00000935348, ENST00000935349, ENST00000955984, ENST00000955985, ENST00000955986

RefSeq mRNA: 8 — MANE Select: NM_000970 NM_000970, NM_001024662, NM_001320137, NM_001320138, NM_001320139, NM_001320140, NM_001320141, NM_001320142

CCDS: CCDS9162

Canonical transcript exons

ENST00000202773 — 7 exons

Exon	Start	End
ENSE00000755322	112405853	112406037
ENSE00001322281	112405189	112405376
ENSE00003464452	112409587	112409605
ENSE00003510127	112408240	112408338
ENSE00003541076	112406294	112406342
ENSE00003700377	112408420	112408656
ENSE00003785471	112406747	112406890

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 99.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 68.8233 / max 1041.5104, expressed in 1820 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133335	62.5412	1815
133332	2.4554	1267
133337	1.5791	736
133330	0.8851	503
133334	0.6993	325
133331	0.4258	183
133333	0.2374	74

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.91	gold quality
ganglionic eminence	UBERON:0004023	99.90	gold quality
embryo	UBERON:0000922	99.89	gold quality
ventricular zone	UBERON:0003053	99.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.85	gold quality
islet of Langerhans	UBERON:0000006	99.81	gold quality
pituitary gland	UBERON:0000007	99.81	gold quality
calcaneal tendon	UBERON:0003701	99.81	gold quality
lymph node	UBERON:0000029	99.80	gold quality
left ovary	UBERON:0002119	99.80	gold quality
monocyte	CL:0000576	99.79	gold quality
leukocyte	CL:0000738	99.79	gold quality
ovary	UBERON:0000992	99.79	gold quality
smooth muscle tissue	UBERON:0001135	99.79	gold quality
right ovary	UBERON:0002118	99.78	gold quality
adenohypophysis	UBERON:0002196	99.78	gold quality
endocervix	UBERON:0000458	99.77	gold quality
rectum	UBERON:0001052	99.77	gold quality
fallopian tube	UBERON:0003889	99.77	gold quality
body of uterus	UBERON:0009853	99.77	gold quality
granulocyte	CL:0000094	99.76	gold quality
pancreas	UBERON:0001264	99.76	gold quality
stromal cell of endometrium	CL:0002255	99.75	gold quality
fundus of stomach	UBERON:0001160	99.75	gold quality
cortex of kidney	UBERON:0001225	99.75	gold quality
myometrium	UBERON:0001296	99.75	gold quality
mammary gland	UBERON:0001911	99.75	gold quality
thyroid gland	UBERON:0002046	99.75	gold quality
corpus callosum	UBERON:0002336	99.75	gold quality
tonsil	UBERON:0002372	99.75	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	3090.81
E-CURD-88	yes	59.78
E-CURD-122	yes	58.71
E-MTAB-9221	yes	55.60
E-HCAD-11	yes	53.47
E-MTAB-6678	yes	40.09
E-HCAD-9	yes	27.47
E-MTAB-10042	yes	16.50
E-MTAB-9067	yes	10.34
E-CURD-112	yes	9.85
E-HCAD-35	yes	8.39
E-MTAB-9801	yes	5.87
E-MTAB-11121	no	7033.76
E-HCAD-4	no	5984.86
E-MTAB-7407	no	5256.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• The high expression of RPL6/Taxreb107 in drug resistant gastric cancer cell shows its correlation with multiple-drug resistance in gastric cancer. (PMID:12678981)
• RPL6 was overexpressed in human gastric cancer and its over-expression could promote cell growth and cell cycle progression at least through upregulating cyclin E expression. (PMID:20171175)
• Down-regulation of RPL6 could suppress cell growth and cell cycle progression at least through down-regulating cyclin E (PMID:22043320)
• The ribosomal protein L6 binds to and suppresses the E3 ubiquitin ligase activity of HDM2, and subsequently attenuates HDM2-mediated p53 polyubiquitination and degradation. (PMID:24174547)
• 60S ribosomal proteins L6 (RPL6) and RPL28, which are adjacent on the ribosome, play opposite roles in generating an influenza A virus-encoded peptide. Depleting RPL6 decreases ubiquitin-dependent peptide presentation, whereas depleting RPL28 increases ubiquitin-dependent and -independent peptide presentation. (PMID:30712990)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl6	ENSDARG00000058451
mus_musculus	Rpl6	ENSMUSG00000029614
rattus_norvegicus		ENSRNOG00000078018
drosophila_melanogaster	RpL6	FBGN0039857
caenorhabditis_elegans		WBGENE00004417

Protein

Protein identifiers

Large ribosomal subunit protein eL6 — Q02878 (reviewed: Q02878)

Alternative names: 60S ribosomal protein L6, Neoplasm-related protein C140, Tax-responsive enhancer element-binding protein 107

All UniProt accessions (7): Q02878, F8VR69, F8VU16, F8VWR1, F8VZ45, F8VZA3, U3KQR5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. (Microbial infection) Specifically binds to domain C of the Tax-responsive enhancer element in the long terminal repeat of HTLV-I.

Subunit / interactions. Component of the large ribosomal subunit. May bind IPO9 with low affinity.

Subcellular location. Cytoplasm. Cytosol. Rough endoplasmic reticulum.

Similarity. Belongs to the eukaryotic ribosomal protein eL6 family.

RefSeq proteins (8): NP_000961, NP_001019833, NP_001307066, NP_001307067, NP_001307068, NP_001307069, NP_001307070, NP_001307071 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000915	60S_ribosomal_eL6	Family
IPR005568	Ribosomal_uL6_N	Domain
IPR008991	Translation_prot_SH3-like_sf	Homologous_superfamily
IPR014722	Rib_uL2_dom2	Homologous_superfamily
IPR041997	Ribosomal_eL6_KOW	Domain
IPR049633	Ribosomal_eL6_CS	Conserved_site

Pfam: PF01159, PF03868

UniProt features (17 total): sequence conflict 4, modified residue 4, sequence variant 3, compositionally biased region 2, initiator methionine 1, chain 1, region of interest 1, cross-link 1

Structure

Experimental structures (PDB)

196 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8A3D	ELECTRON MICROSCOPY	1.67
8GLP	ELECTRON MICROSCOPY	1.67
8QYX	ELECTRON MICROSCOPY	1.78
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8QFD	ELECTRON MICROSCOPY	2.2
8YOP	ELECTRON MICROSCOPY	2.2
9GUL	ELECTRON MICROSCOPY	2.2
9O3V	ELECTRON MICROSCOPY	2.2
9O3Y	ELECTRON MICROSCOPY	2.2
8JDK	ELECTRON MICROSCOPY	2.26
8G5Y	ELECTRON MICROSCOPY	2.29
9S3D	ELECTRON MICROSCOPY	2.32
9RPV	ELECTRON MICROSCOPY	2.35
9S3B	ELECTRON MICROSCOPY	2.38
7OW7	ELECTRON MICROSCOPY	2.4
8K2C	ELECTRON MICROSCOPY	2.4
8XSX	ELECTRON MICROSCOPY	2.4
9SPF	ELECTRON MICROSCOPY	2.4
9SPI	ELECTRON MICROSCOPY	2.4
8JDL	ELECTRON MICROSCOPY	2.42
9S3C	ELECTRON MICROSCOPY	2.42
8FKV	ELECTRON MICROSCOPY	2.47
9QLO	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48
9P8B	ELECTRON MICROSCOPY	2.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02878-F1	83.21	0.63

Functional residue map

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

Post-translational modifications (5): 94, 127, 207, 239, 5

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: 299 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_CYTOPLASMIC_TRANSLATION, SWEET_KRAS_ONCOGENIC_SIGNATURE, MODULE_151, GCM_NPM1, MORF_UBE2I, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, GCM_PSME1, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_MUSCLE_CONTRACTION

GO Biological Process (3): cytoplasmic translation (GO:0002181), regulation of DNA-templated transcription (GO:0006355), translation (GO:0006412)

GO Molecular Function (5): DNA binding (GO:0003677), RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (15): nucleus (GO:0005634), cytoplasm (GO:0005737), rough endoplasmic reticulum (GO:0005791), 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), endoplasmic reticulum (GO:0005783), ribosome (GO:0005840), large ribosomal subunit (GO:0015934), synapse (GO:0045202), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Ribosome-associated quality control	3
Translation	2
Cap-dependent Translation Initiation	2
Nonsense-Mediated Decay (NMD)	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	1
rRNA processing in the nucleus and cytosol	1
Signaling by ROBO receptors	1
Cellular response to starvation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	3
nucleic acid binding	2
ribosome	2
intracellular membrane-bounded organelle	2
translation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
structural molecule activity	1
cell adhesion molecule binding	1
binding	1
intracellular anatomical structure	1
endoplasmic reticulum	1
cell-substrate junction	1
asymmetric synapse	1
postsynaptic specialization	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
ribonucleoprotein granule	1
endomembrane system	1
intracellular membraneless organelle	1
ribosomal subunit	1
cell junction	1
protein-containing complex	1

Protein interactions and networks

STRING

3774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL6	RPL7	P18124	892
RPL6	RPS6	P08227	861
RPL6	RPL14	P50914	843
RPL6	RPL4	P36578	841
RPL6	RPS14	P06366	826
RPL6	RPL5	P46777	815
RPL6	RPL11	P25121	815
RPL6	RPL23A	P29316	811
RPL6	RPL8	P25120	797
RPL6	RPL3	P39023	796
RPL6	RPS19	P39019	789
RPL6	RPL12	P30050	784
RPL6	RPS9	P46781	784
RPL6	RPL27A	P46776	782
RPL6	RPL26	P61254	779

IntAct

265 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
STAU1	RPLP0	psi-mi:“MI:0914”(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
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
INAVA	CYTH3	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
NOM1	RPLP0	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
MAGEB10	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL6	MRPS14	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (999): RPL6 (Affinity Capture-MS), RPL6 (Affinity Capture-MS), RPL6 (Affinity Capture-MS), RPL6 (Affinity Capture-MS), RPL6 (Affinity Capture-MS), RPL6 (Affinity Capture-MS), RPL6 (Affinity Capture-MS), RPL6 (Affinity Capture-MS), RPL6 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), RPL26L1 (Affinity Capture-MS), YBX1 (Affinity Capture-MS), MRPS9 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), NGRN (Affinity Capture-MS)

ESM2 similar proteins: A1XQU3, A1XQU5, G1SE28, G1SKF7, G1SZ12, G1TXF6, O65743, O94776, P21533, P37108, P38666, P47911, P50888, P50914, P55844, P61122, P61353, P61354, P61355, P61356, P61357, P61358, P83731, P83732, Q02878, Q2YGT9, Q3T0U2, Q42347, Q4R5C7, Q4R8Z4, Q58DQ3, Q63507, Q66WF5, Q6QMZ4, Q6Y263, Q862I1, Q8BP67, Q8ISQ3, Q8JGR4, Q90YQ0

Diamond homologs: A0A1D8PCX8, A1RXE1, A2BME7, A4WH36, A4YCT0, A8ABY5, B1YA63, C3MR21, C3MXC5, C3MZ69, C3N789, C3NGE6, C4KIE7, G1SKF7, O15595, P05739, P0DJ56, P21533, P34091, P47911, P47991, P79071, Q02326, Q02878, Q2YGT9, Q4JAJ9, Q54D63, Q58DQ3, Q6QMZ4, Q8TX43, Q975L7, Q980C1, Q9C9C5, Q9C9C6, Q9FZ76, A1RTL6, A3DND4, A3MS76, B8D5U3, Q8ZYB4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MDM2	“down-regulates quantity by destabilization”	RPL6	ubiquitination
RPL6	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 227 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
Nuclear events stimulated by ALK signaling in cancer	5	10.8×	3e-03
RHOV GTPase cycle	5	9.4×	6e-03
Mitochondrial translation	10	9.1×	2e-05
Peptide chain elongation	10	8.4×	2e-05
Viral mRNA Translation	10	8.4×	2e-05
Mitochondrial translation initiation	10	8.4×	2e-05
Mitochondrial translation elongation	10	8.4×	2e-05
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	10	8.3×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
stress granule assembly	6	18.7×	1e-04
mRNA stabilization	7	13.3×	1e-04
cytoplasmic translation	12	11.5×	4e-07
intrinsic apoptotic signaling pathway	6	11.2×	2e-03
negative regulation of translation	10	10.2×	2e-05
translation	17	9.1×	8e-09
mitochondrial translation	10	9.0×	4e-05
rRNA processing	12	8.8×	5e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

749 predictions. Top by Δscore:

Variant	Effect	Δscore
12:112405372:TATTT:T	acceptor_gain	1.0000
12:112405374:TTT:T	acceptor_gain	1.0000
12:112405375:TT:T	acceptor_gain	1.0000
12:112405375:TTCTA:T	acceptor_loss	1.0000
12:112405376:TCTA:T	acceptor_loss	1.0000
12:112405377:C:CC	acceptor_gain	1.0000
12:112405378:T:C	acceptor_loss	1.0000
12:112405848:CTTA:C	donor_loss	1.0000
12:112405850:TA:T	donor_loss	1.0000
12:112405851:A:AC	donor_gain	1.0000
12:112405851:AC:A	donor_gain	1.0000
12:112405851:ACCT:A	donor_gain	1.0000
12:112405852:C:CT	donor_gain	1.0000
12:112405852:CC:C	donor_gain	1.0000
12:112405852:CCT:C	donor_gain	1.0000
12:112405852:CCTC:C	donor_gain	1.0000
12:112405852:CCTCT:C	donor_gain	1.0000
12:112406033:AGGTC:A	acceptor_gain	1.0000
12:112406034:GGTC:G	acceptor_gain	1.0000
12:112406035:GTC:G	acceptor_gain	1.0000
12:112406036:TC:T	acceptor_gain	1.0000
12:112406037:CC:C	acceptor_gain	1.0000
12:112406038:C:CC	acceptor_gain	1.0000
12:112406038:C:T	acceptor_gain	1.0000
12:112406038:CT:C	acceptor_loss	1.0000
12:112406338:ACCCT:A	acceptor_gain	1.0000
12:112406339:CCCT:C	acceptor_gain	1.0000
12:112406339:CCCTC:C	acceptor_gain	1.0000
12:112406340:CCTC:C	acceptor_gain	1.0000
12:112406341:CT:C	acceptor_gain	1.0000

AlphaMissense

1861 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:112405868:G:C	F233L	1.000
12:112405868:G:T	F233L	1.000
12:112405870:A:G	F233L	1.000
12:112406003:T:A	R188S	1.000
12:112406003:T:G	R188S	1.000
12:112406004:C:G	R188T	1.000
12:112406037:C:T	G177E	1.000
12:112406294:C:G	G177R	1.000
12:112406294:C:T	G177R	1.000
12:112406763:C:T	G155E	1.000
12:112405227:G:C	F288L	0.999
12:112405227:G:T	F288L	0.999
12:112405229:A:G	F288L	0.999
12:112405266:A:C	F275L	0.999
12:112405266:A:T	F275L	0.999
12:112405268:A:G	F275L	0.999
12:112405331:C:G	D254H	0.999
12:112405341:C:A	Q250H	0.999
12:112405341:C:G	Q250H	0.999
12:112405342:T:G	Q250P	0.999
12:112405355:G:T	R246S	0.999
12:112405869:A:C	F233C	0.999
12:112405869:A:G	F233S	0.999
12:112405870:A:C	F233V	0.999
12:112405872:A:G	I232T	0.999
12:112405916:G:C	F217L	0.999
12:112405916:G:T	F217L	0.999
12:112405918:A:G	F217L	0.999
12:112405980:G:T	A196D	0.999
12:112405983:A:T	I195N	0.999

dbSNP variants (sampled 300 via entrez): RS1000351925 (12:112409564 G>A,C,T), RS1000417649 (12:112416842 G>A), RS1000592698 (12:112409787 G>A), RS1000624030 (12:112410073 G>A), RS1000844432 (12:112417516 T>C), RS1001276264 (12:112415132 G>A), RS1001565696 (12:112417128 G>A), RS1001645557 (12:112408927 G>A,C), RS1001670571 (12:112418125 G>GC), RS1002271298 (12:112410417 TA>T,TAA,TAAA), RS1002570079 (12:112407829 G>A), RS1002570344 (12:112414913 C>A), RS1002594077 (12:112407409 A>G,T), RS1002633144 (12:112407724 CTT>C,CTTT), RS1003249908 (12:112419829 T>C)

Disease associations

OMIM: gene MIM:603703 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001072_7	Blood pressure	8.000000e-31
GCST001074_7	Blood pressure	1.000000e-35
GCST001089_3	Esophageal cancer	2.000000e-15
GCST003272_10	Systolic blood pressure	7.000000e-09
GCST003273_11	Diastolic blood pressure	2.000000e-11
GCST005329_1	Coffee consumption	2.000000e-16
GCST005951_1	Body mass index	4.000000e-12
GCST006988_125	Blond vs. brown/black hair color	4.000000e-08
GCST90020028_949	Hip circumference adjusted for BMI	4.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0006782	cups of coffee per day measurement
EFO:0004340	body mass index
EFO:0003924	hair color
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067542 (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

46 potent at pChembl≥5 of 52 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 207 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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	increases abundance, affects cotreatment, increases oxidation	2
Doxorubicin	affects expression, decreases response to substance	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Rotenone	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
cinobufagin	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	increases expression	1
afimoxifene	decreases expression	1
1,2-dielaidoylphosphatidylethanolamine	decreases expression	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	increases expression	1
azoxystrobin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	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.