RPL7

Summary

RPL7 (ribosomal protein L7, HGNC:10363) is a protein-coding gene on chromosome 8q21.11, encoding Large ribosomal subunit protein uL30 (P18124). Component of the large ribosomal subunit. 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 belongs to the L30P family of ribosomal proteins. It contains an N-terminal basic region-leucine zipper (BZIP)-like domain and the RNP consensus submotif RNP2. In vitro the BZIP-like domain mediates homodimerization and stable binding to DNA and RNA, with a preference for 28S rRNA and mRNA. The protein can inhibit cell-free translation of mRNAs, suggesting that it plays a regulatory role in the translation apparatus. It is located in the cytoplasm. The protein has been shown to be an autoantigen in patients with systemic autoimmune diseases, such as systemic lupus erythematosus. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6129 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 49 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_000971

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10363
Approved symbol	RPL7
Name	ribosomal protein L7
Location	8q21.11
Locus type	gene with protein product
Status	Approved
Aliases	humL7-1, L7, uL30
Ensembl gene	ENSG00000147604
Ensembl biotype	protein_coding
OMIM	604166
Entrez	6129

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000352983, ENST00000396465, ENST00000396466, ENST00000396467, ENST00000431653, ENST00000435330, ENST00000466821, ENST00000487500, ENST00000863689, ENST00000863690

RefSeq mRNA: 2 — MANE Select: NM_000971 NM_000971, NM_001363737

CCDS: CCDS6212, CCDS87615

Canonical transcript exons

ENST00000352983 — 7 exons

Exon	Start	End
ENSE00000980840	73292239	73292405
ENSE00000980841	73291773	73291910
ENSE00000980842	73291552	73291661
ENSE00000980843	73291043	73291252
ENSE00001016700	73293599	73293633
ENSE00001875584	73290242	73290705
ENSE00003482309	73292689	73292797

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.0442 / max 88.6392, expressed in 1629 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93585	1.8891	1051
93586	1.5811	762
93589	0.6686	431
93584	0.5842	282
93588	0.2783	122
93587	0.0429	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.96	gold quality
ventricular zone	UBERON:0003053	99.95	gold quality
calcaneal tendon	UBERON:0003701	99.95	gold quality
cortical plate	UBERON:0005343	99.94	gold quality
mucosa of stomach	UBERON:0001199	99.91	gold quality
left ovary	UBERON:0002119	99.91	gold quality
right ovary	UBERON:0002118	99.90	gold quality
monocyte	CL:0000576	99.89	gold quality
leukocyte	CL:0000738	99.89	gold quality
endocervix	UBERON:0000458	99.89	gold quality
colonic epithelium	UBERON:0000397	99.88	gold quality
smooth muscle tissue	UBERON:0001135	99.88	gold quality
skin of abdomen	UBERON:0001416	99.88	gold quality
body of uterus	UBERON:0009853	99.88	gold quality
rectum	UBERON:0001052	99.87	gold quality
ectocervix	UBERON:0012249	99.87	gold quality
right uterine tube	UBERON:0001302	99.86	gold quality
left uterine tube	UBERON:0001303	99.86	gold quality
popliteal artery	UBERON:0002250	99.86	gold quality
tibial artery	UBERON:0007610	99.86	gold quality
metanephros cortex	UBERON:0010533	99.86	gold quality
left lobe of thyroid gland	UBERON:0001120	99.85	gold quality
body of pancreas	UBERON:0001150	99.85	gold quality
tibial nerve	UBERON:0001323	99.85	gold quality
gall bladder	UBERON:0002110	99.85	gold quality
right lung	UBERON:0002167	99.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.85	gold quality
right lobe of thyroid gland	UBERON:0001119	99.84	gold quality
vermiform appendix	UBERON:0001154	99.84	gold quality
body of stomach	UBERON:0001161	99.84	gold quality

Single-cell (SCXA)

Detected in 44 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-CURD-97	yes	9355.67
E-MTAB-10662	yes	8346.54
E-MTAB-8142	yes	6697.39
E-HCAD-9	yes	4144.00
E-MTAB-5061	yes	3940.80
E-GEOD-81547	yes	3842.29
E-MTAB-9221	yes	3496.70
E-MTAB-10042	yes	2708.02
E-CURD-122	yes	80.38
E-CURD-88	yes	51.09
E-CURD-46	yes	49.35
E-MTAB-6678	yes	38.86
E-CURD-112	yes	32.68
E-GEOD-137537	yes	32.47
E-MTAB-9067	yes	30.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EN2, MYC, ZBTB4

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 7)

• Combining with the phylogenic findings from homologous sequence alignment, the NH2-region of L7, besides being as a eukaryotic expansion segment, can be excluded from building a functional eukaryotic ribosome. (PMID:16797011)
• L7-endoplasmic reticulum-binding nature could be one of multiple factors that allow a nascent peptide-less ribosome to remain at the endoplasmic reticulum. (PMID:17258209)
• importin beta3 is essential for the nuclear import of RPL7. The import is mediated via the multifaceted basic amino acid clusters present in the NH(2)-region of RPL7, and is RanGTP-dependent (PMID:20828572)
• RPL7 gene expression is decreased in follicular variant of papillary thyroid carcinoma. (PMID:21509594)
• In case of L7, importin beta2 or importin beta3 are preferentially used by clusters with a high import efficiency. (PMID:23266416)
• HIV-1 Gag NC domain interacts with the ribosomal protein RPL7 endowed with nucleic acid chaperone activity, favoring the notion that RPL7 could be a Gag helper chaperoning factor possibly contributing to the start of Gag assembly (PMID:27515235)
• The nucleic acid chaperone activity of the HIV-1 Gag polyprotein is boosted by its cellular partner RPL7: a kinetic study. (PMID:32797159)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl7	ENSDARG00000007320
rattus_norvegicus	Rpl7-ps3	ENSRNOG00000031912
drosophila_melanogaster	RpL7	FBGN0005593
caenorhabditis_elegans	rpl-7	WBGENE00004418

Paralogs (1): RPL7L1 (ENSG00000146223)

Protein

Protein identifiers

Large ribosomal subunit protein uL30 — P18124 (reviewed: P18124)

Alternative names: 60S ribosomal protein L7

All UniProt accessions (4): P18124, A8MUD9, C9JIJ5, C9JZ88

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. Binds to G-rich structures in 28S rRNA and in mRNAs. Plays a regulatory role in the translation apparatus; inhibits cell-free translation of mRNAs.

Subunit / interactions. Component of the large ribosomal subunit. Homodimer. Interacts with DHX33.

Subcellular location. Cytoplasm.

Similarity. Belongs to the universal ribosomal protein uL30 family.

RefSeq proteins (2): NP_000962, NP_001350666 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005998	Ribosomal_uL30_euk	Family
IPR012988	Ribosomal_uL30_N_euk	Domain
IPR016082	Ribosomal_uL30_ferredoxin-like	Domain
IPR018038	Ribosomal_uL30_CS	Conserved_site
IPR035808	Ribosomal_uL30_euk_arc	Domain
IPR036919	Ribo_uL30_ferredoxin-like_sf	Homologous_superfamily
IPR039699	Ribosomal_uL30	Family

Pfam: PF00327, PF08079

UniProt features (17 total): sequence conflict 6, modified residue 5, repeat 4, chain 1, region of interest 1

Structure

Experimental structures (PDB)

194 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-P18124-F1	94.06	0.93

Functional residue map

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

Post-translational modifications (5): 139, 1, 17, 124, 127

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: 252 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_CYTOPLASMIC_TRANSLATION, RRAGTTGT_UNKNOWN, GOBP_RIBOSOME_BIOGENESIS, MODULE_151, GCM_NPM1, MORF_UBE2I, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, AACWWCAANK_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, GCM_PSME1, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT

GO Biological Process (5): maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000463), cytoplasmic translation (GO:0002181), rRNA processing (GO:0006364), translation (GO:0006412), ribosomal large subunit biogenesis (GO:0042273)

GO Molecular Function (6): DNA binding (GO:0003677), RNA binding (GO:0003723), mRNA binding (GO:0003729), structural constituent of ribosome (GO:0003735), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), nucleolus (GO:0005730), 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), ribonucleoprotein complex (GO:1990904), ribosome (GO:0005840)

Reactome top-level categories

Rollup of top-11 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
ribosome biogenesis	2
nucleic acid binding	2
ribosome	2
intracellular membrane-bounded organelle	2
intracellular membraneless organelle	2
cytoplasm	2
maturation of LSU-rRNA	1
translation	1
RNA processing	1
rRNA metabolic 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
ribonucleoprotein complex biogenesis	1
RNA binding	1
structural molecule activity	1
protein binding	1
binding	1
nuclear lumen	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
protein-containing complex	1

Protein interactions and networks

STRING

4342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL7	RPS24	P16632	903
RPL7	RPL6	Q02878	892
RPL7	RPS6	P08227	880
RPL7	RPL12	P30050	823
RPL7	RPS20	P17075	821
RPL7	RPS19	P39019	814
RPL7	RPL5	P46777	798
RPL7	RPL11	P25121	791
RPL7	RPS3A	P33443	785
RPL7	RPL4	P36578	781
RPL7	RPL9	P32969	771
RPL7	RPL3	P39023	768
RPL7	RPL14	P50914	761
RPL7	RPL21	P46778	760
RPL7	RPL8	P25120	759

IntAct

277 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
ATXN2	PABPC1	psi-mi:“MI:0915”(physical association)	0.820
RACK1	RPL7	psi-mi:“MI:0403”(colocalization)	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
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	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
NSA2	TYW5	psi-mi:“MI:0914”(association)	0.530
MAGEB10	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPL7	ZBTB24	psi-mi:“MI:0914”(association)	0.530
RPL26	RPL7	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	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 (798): RPL7 (Affinity Capture-MS), RPL7 (Affinity Capture-MS), RPL7 (Affinity Capture-MS), RPL7 (Biochemical Activity), RPL7 (Affinity Capture-MS), RPL7 (Affinity Capture-MS), RPL7 (Affinity Capture-MS), RPL7 (Affinity Capture-MS), ABCE1 (Co-fractionation), BRIX1 (Co-fractionation), CAPRIN1 (Co-fractionation), DDX24 (Co-fractionation), EEF1A1 (Co-fractionation), EIF3C (Co-fractionation), GNB2L1 (Co-fractionation)

ESM2 similar proteins: A0A1D8PDL6, A0A1D8PK43, A0BD73, A0CEY2, A5GFQ0, A9A597, O01802, O42848, O42991, O43004, O60143, P05426, P05737, P0CX49, P0CX50, P0DJ13, P0DJ15, P0DJ17, P11874, P14148, P17937, P18124, P25457, P26784, P26785, P32100, P32101, P60039, P60040, Q12213, Q12ZT0, Q27389, Q4DZP2, Q4R506, Q58DT1, Q5AB87, Q5R9R4, Q5RAH8, Q5ZJ56, Q6BIF5

Diamond homologs: A0A1D8PDL6, A0BD73, A0CEY2, A5GFQ0, G1SV32, O01802, O60143, P05426, P05737, P0DJ13, P11874, P14148, P17937, P18124, P25457, P32100, P32101, P32102, P40693, P60039, P60040, Q12213, Q4R506, Q58DT1, Q5R9R4, Q5RAH8, Q5ZJ56, Q6BIF5, Q6BTA4, Q6C603, Q6DKI1, Q6FS36, Q6FSN6, Q755A7, Q75ET5, Q7SBD5, Q8SS93, Q9D8M4, Q9HH78, Q9LHP1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL7	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 197 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
TRAF6 mediated NF-kB activation	7	23.0×	7e-07
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	16	13.6×	1e-11
TAK1-dependent IKK and NF-kappa-B activation	6	13.0×	2e-04
SRP-dependent cotranslational protein targeting to membrane	17	12.2×	1e-11
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	17	11.9×	1e-11
Peptide chain elongation	13	11.9×	4e-09
Viral mRNA Translation	13	11.9×	4e-09
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	13	11.7×	5e-09

GO biological processes:

GO term	Partners	Fold	FDR
stress granule assembly	5	17.5×	1e-03
cytoplasmic translation	16	17.2×	1e-12
mRNA stabilization	7	14.9×	1e-04
ribosomal large subunit biogenesis	5	12.9×	4e-03
translational initiation	6	12.5×	1e-03
stem cell population maintenance	5	12.2×	4e-03
negative regulation of translation	9	10.2×	7e-05
translation	16	9.6×	7e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

716 predictions. Top by Δscore:

Variant	Effect	Δscore
8:73291037:TCTCA:T	donor_loss	1.0000
8:73291038:CTCAC:C	donor_loss	1.0000
8:73291039:TCACC:T	donor_loss	1.0000
8:73291040:CA:C	donor_loss	1.0000
8:73291042:C:CA	donor_loss	1.0000
8:73291248:TTTAC:T	acceptor_gain	1.0000
8:73291249:TTAC:T	acceptor_gain	1.0000
8:73291250:TAC:T	acceptor_gain	1.0000
8:73291251:ACC:A	acceptor_loss	1.0000
8:73291253:CT:C	acceptor_loss	1.0000
8:73291257:A:C	acceptor_gain	1.0000
8:73291259:A:C	acceptor_gain	1.0000
8:73291547:CCTA:C	donor_loss	1.0000
8:73291550:A:AC	donor_gain	1.0000
8:73291550:ACC:A	donor_loss	1.0000
8:73291551:C:CC	donor_gain	1.0000
8:73291578:T:C	donor_gain	1.0000
8:73291657:GGTAC:G	acceptor_gain	1.0000
8:73291658:GTAC:G	acceptor_gain	1.0000
8:73291659:TAC:T	acceptor_gain	1.0000
8:73291659:TACCT:T	acceptor_loss	1.0000
8:73291660:AC:A	acceptor_gain	1.0000
8:73291660:ACCTG:A	acceptor_loss	1.0000
8:73291661:CC:C	acceptor_gain	1.0000
8:73291661:CCTG:C	acceptor_loss	1.0000
8:73291662:C:CC	acceptor_gain	1.0000
8:73291663:T:A	acceptor_loss	1.0000
8:73291667:G:C	acceptor_gain	1.0000
8:73291667:G:GC	acceptor_gain	1.0000
8:73291768:CTTA:C	donor_loss	1.0000

AlphaMissense

1633 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:73291774:C:A	G143W	0.999
8:73291774:C:G	G143R	0.999
8:73291774:C:T	G143R	0.999
8:73291842:C:T	G120E	0.999
8:73291083:C:A	R236S	0.998
8:73291083:C:G	R236S	0.998
8:73291084:C:A	R236M	0.998
8:73291110:A:C	F227L	0.998
8:73291110:A:T	F227L	0.998
8:73291112:A:G	F227L	0.998
8:73291656:G:T	P145H	0.998
8:73291773:C:T	G143E	0.998
8:73291777:A:G	W142R	0.998
8:73291777:A:T	W142R	0.998
8:73291860:A:G	L114P	0.998
8:73291860:A:T	L114H	0.998
8:73292240:C:G	G97R	0.998
8:73292247:T:A	R94S	0.998
8:73292247:T:G	R94S	0.998
8:73292248:C:G	R94T	0.998
8:73291084:C:G	R236T	0.997
8:73291153:A:G	L213S	0.997
8:73291188:G:C	F201L	0.997
8:73291188:G:T	F201L	0.997
8:73291190:A:G	F201L	0.997
8:73291632:A:G	L153P	0.997
8:73291773:C:A	G143V	0.997
8:73291836:A:G	F122S	0.997
8:73291869:A:G	L111P	0.997
8:73292248:C:A	R94I	0.997

dbSNP variants (sampled 300 via entrez): RS1000559104 (8:73294552 G>C), RS1000876795 (8:73294659 C>G,T), RS1000935960 (8:73290255 G>A), RS1001045157 (8:73294540 C>G), RS1001351954 (8:73294322 G>A), RS1002383271 (8:73294505 G>A), RS1002444509 (8:73289887 G>A), RS1002585280 (8:73294932 G>A), RS1002739412 (8:73294334 G>A), RS1003788080 (8:73295691 A>G), RS1003961181 (8:73289893 A>C), RS1003973098 (8:73295810 C>A,G,T), RS1004004162 (8:73295601 C>A,T), RS1004121492 (8:73290542 T>A,C), RS1005073920 (8:73294083 G>C)

Disease associations

OMIM: gene MIM:604166 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001438_7	Crohn’s disease	2.000000e-08
GCST010456_4	Anthracycline-induced cardiotoxicity in early breast cancer	6.000000e-06
GCST011983_13	Fasting glucose	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005257	response to anthracycline-based chemotherapy
EFO:1001482	cardiotoxicity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066948 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

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

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

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

ChEMBL bioactivities

48 potent at pChembl≥5 of 54 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.78	Kd	16.7	nM	CHEMBL3752910
7.78	ED50	16.7	nM	CHEMBL3752910
6.52	IC50	300	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4574496
6.41	IC50	390	nM	CHEMBL4126894
6.39	IC50	410	nM	CHEMBL4114159
6.35	IC50	450	nM	CHEMBL4126496
6.30	IC50	500	nM	CHEMBL4574496
6.30	IC50	500	nM	CHEMBL4560206
6.16	IC50	690	nM	CHEMBL4130157
6.15	IC50	710	nM	CHEMBL4108338
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	IC50	900	nM	CHEMBL4126894
6.05	IC50	900	nM	CHEMBL4126496
6.04	IC50	920	nM	CHEMBL4554909
5.97	IC50	1060	nM	CHEMBL4128388
5.89	IC50	1290	nM	CHEMBL4130157
5.86	IC50	1370	nM	CHEMBL4107559
5.84	IC50	1440	nM	CHEMBL4108338
5.81	IC50	1540	nM	CHEMBL4534859
5.76	IC50	1730	nM	CHEMBL4534859
5.69	IC50	2050	nM	CHEMBL4566239
5.68	IC50	2080	nM	CHEMBL4446635
5.66	IC50	2210	nM	CHEMBL4446635
5.66	EC50	2200	nM	CHEMBL4464929
5.64	IC50	2270	nM	CHEMBL4533299
5.63	IC50	2330	nM	CHEMBL4566239
5.62	IC50	2380	nM	CHEMBL4128388
5.58	IC50	2630	nM	CHEMBL4128250
5.55	IC50	2820	nM	CHEMBL4127458
5.53	IC50	2970	nM	CHEMBL4127311
5.51	IC50	3080	nM	CHEMBL4126072
5.46	IC50	3500	nM	CHEMBL4525277
5.44	IC50	3630	nM	CHEMBL4469712
5.39	IC50	4100	nM	CHEMBL4128560
5.37	IC50	4300	nM	CHEMBL4127016
5.36	IC50	4380	nM	CHEMBL4527910
5.16	IC50	7000	nM	CHEMBL4109308
5.13	IC50	7400	nM	CHLORAMPHENICOL SULFATE SALT
5.09	IC50	8040	nM	CHEMBL4128250
5.08	IC50	8370	nM	CHEMBL4128250
5.03	IC50	9320	nM	CHEMBL4127016
5.03	IC50	9240	nM	CHEMBL4128560

PubChem BioAssay actives

47 with measured affinity, of 209 total; 27 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149273: Binding affinity to human RPL7 incubated for 45 mins by Kinobead based pull down assay	kd	0.0167	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1585498: Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method	ic50	0.3000	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-3-[4-(triazolo[4,5-b]pyridin-3-yl)phenyl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3800	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3900	uM
N-(3-chloro-2-pyridinyl)-4-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4100	uM
N-(3-chloro-2-pyridinyl)-4-(5-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4500	uM
N-(1-methylpyrrolo[2,3-c]pyridin-7-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.5000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.6900	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-5-(triazolo[4,5-b]pyridin-3-yl)pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.7100	uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylpiperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.9200	uM
N-isoquinolin-1-yl-4-(1-methylpyrazol-4-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	1.0600	uM
N-isoquinolin-1-yl-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	1.5400	uM
N-(3-methyl-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.0500	uM
N-(3-chloro-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	2.0800	uM
N-(5,8-dihydroisoquinolin-1-yl)-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1584424: Inhibition of human 80S ribosome-mediated PCSK9 translation expressed in CHO-K1 cells assessed as reduction in PCSK9 secretion	ec50	2.2000	uM
N-isoquinolin-1-yl-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.6300	uM
N-(3-chloro-2-pyridinyl)-4-(6-methylpyrazin-2-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.8200	uM
N-(3-chloro-2-pyridinyl)-4-[6-(dimethylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.9700	uM
N-(3-chloro-2-pyridinyl)-4-[6-(methylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	3.0800	uM
N-isoquinolin-1-yl-4-(6-methyl-1,2-benzoxazol-3-yl)-N-[(3R)-piperidin-3-yl]piperazine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	3.5000	uM
N-(3-methylpyrazin-2-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	3.6300	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-6-(triazolo[4,5-b]pyridin-3-yl)pyridine-3-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.1000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazin-2-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.3000	uM
4-(2-fluorophenyl)-N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	4.3800	uM
2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide;sulfuric acid	717551: Inhibition of mitochondrial ribosome-mediated protein synthesis in human HeLa cells assessed as {35S]methionine incorporation by autoradiography	ic50	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Valproic Acid	decreases expression, affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases expression	2
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	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
3,3’-diindolylmethane	decreases reaction, increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
epigallocatechin gallate	increases expression	1
JP8 aviation fuel	decreases expression	1
chloropicrin	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
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	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.