RPL7A

Summary

RPL7A (ribosomal protein L7a, HGNC:10364) is a protein-coding gene on chromosome 9q34.2, encoding Large ribosomal subunit protein eL8 (P62424). Component of the large ribosomal subunit. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

Cytoplasmic ribosomes, 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 L7AE family of ribosomal proteins. It can interact with a subclass of nuclear hormone receptors, including thyroid hormone receptor, and inhibit their ability to transactivate by preventing their binding to their DNA response elements. This gene is included in the surfeit gene cluster, a group of very tightly linked genes that do not share sequence similarity. It is co-transcribed with the U24, U36a, U36b, and U36c small nucleolar RNA genes, which are located in its second, fifth, fourth, and sixth introns, respectively. This gene rearranges with the trk proto-oncogene to form the chimeric oncogene trk-2h, which encodes an oncoprotein consisting of the N terminus of ribosomal protein L7a fused to the receptor tyrosine kinase domain of trk. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6130 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 37 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_000972

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10364
Approved symbol	RPL7A
Name	ribosomal protein L7a
Location	9q34.2
Locus type	gene with protein product
Status	Approved
Aliases	SURF3, TRUP, L7A, eL8
Ensembl gene	ENSG00000148303
Ensembl biotype	protein_coding
OMIM	185640
Entrez	6130

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 12 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000315731, ENST00000323345, ENST00000426651, ENST00000463740, ENST00000468019, ENST00000485706, ENST00000489392, ENST00000492798, ENST00000496554, ENST00000901515, ENST00000901516, ENST00000930887, ENST00000930888, ENST00000930889, ENST00000930890, ENST00000930891, ENST00000930892, ENST00000930893

RefSeq mRNA: 1 — MANE Select: NM_000972 NM_000972

CCDS: CCDS6965

Canonical transcript exons

ENST00000323345 — 8 exons

Exon	Start	End
ENSE00001456680	133348218	133348246
ENSE00003544752	133349551	133349700
ENSE00003567804	133348922	133349042
ENSE00003577346	133351002	133351071
ENSE00003587234	133350597	133350727
ENSE00003660525	133350240	133350319
ENSE00003670240	133349912	133350052
ENSE00003692020	133351262	133351426

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 161.6688 / max 956.4533, expressed in 1827 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99258	152.1749	1827
99259	6.0619	1651
205650	1.2808	776
99257	0.5214	289
99256	0.4950	200
99261	0.4385	192
99255	0.4261	178
99260	0.2701	101

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.95	gold quality
islet of Langerhans	UBERON:0000006	99.90	gold quality
left ovary	UBERON:0002119	99.90	gold quality
ovary	UBERON:0000992	99.89	gold quality
right adrenal gland	UBERON:0001233	99.89	gold quality
left adrenal gland	UBERON:0001234	99.89	gold quality
right uterine tube	UBERON:0001302	99.89	gold quality
right ovary	UBERON:0002118	99.89	gold quality
fallopian tube	UBERON:0003889	99.89	gold quality
left adrenal gland cortex	UBERON:0035825	99.89	gold quality
right adrenal gland cortex	UBERON:0035827	99.89	gold quality
smooth muscle tissue	UBERON:0001135	99.88	gold quality
pituitary gland	UBERON:0000007	99.87	gold quality
pancreas	UBERON:0001264	99.87	gold quality
adrenal gland	UBERON:0002369	99.87	gold quality
lower esophagus mucosa	UBERON:0035834	99.87	gold quality
zone of skin	UBERON:0000014	99.86	gold quality
endocervix	UBERON:0000458	99.86	gold quality
rectum	UBERON:0001052	99.86	gold quality
body of pancreas	UBERON:0001150	99.86	gold quality
skin of abdomen	UBERON:0001416	99.86	gold quality
skin of leg	UBERON:0001511	99.86	gold quality
adenohypophysis	UBERON:0002196	99.86	gold quality
left testis	UBERON:0004533	99.86	gold quality
right testis	UBERON:0004534	99.86	gold quality
cortical plate	UBERON:0005343	99.86	gold quality
stromal cell of endometrium	CL:0002255	99.85	gold quality
tonsil	UBERON:0002372	99.85	gold quality
esophagus mucosa	UBERON:0002469	99.85	gold quality
ventricular zone	UBERON:0003053	99.85	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	35.34
E-MTAB-9067	yes	27.16
E-HCAD-35	yes	10.02
E-MTAB-9801	yes	5.90
E-MTAB-10287	no	6236.05
E-GEOD-83139	no	2.75
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 4)

• ethanol-induced alteration in expression may mediate the promoting effects of ethanol on breast cancer development (PMID:11759826)
• the L7a protein contains two RNA-binding domains: one encompassing aa 52-100 (RNAB1) and the other encompassing aa 101-161 (RNAB2) (PMID:15361074)
• Under-expression of RPL7A may be involved in the carcinogenesis of osteosarcoma (PMID:19125294)
• X-ray diffraction data of RPL7a were collected to a resolution of 3.5 A from a crystal belonging to the tetragonal space group P4(1)22 or P4(3)22 with unit-cell parameters a = 92.28, b = 92.28, c = 236.59 A (PMID:21505254)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rpl7a	ENSMUSG00000062647
rattus_norvegicus	AABR07072440.1	ENSRNOG00000033030
rattus_norvegicus	AABR07007121.1	ENSRNOG00000033843
drosophila_melanogaster	RpL7A	FBGN0014026
caenorhabditis_elegans		WBGENE00004419

Paralogs (3): NHP2 (ENSG00000145912), RSL1D1 (ENSG00000171490), RPL10A (ENSG00000198755)

Protein

Protein identifiers

Large ribosomal subunit protein eL8 — P62424 (reviewed: P62424)

Alternative names: 60S ribosomal protein L7a, PLA-X polypeptide, Surfeit locus protein 3

All UniProt accessions (3): P62424, Q5T8U2, Q5T8U3

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.

Subunit / interactions. Component of the large ribosomal subunit. Interacts with CRY1. Interacts with DICER1, AGO2, TARBP2, MOV10 and EIF6; they form a large RNA-induced silencing complex (RISC).

Subcellular location. Cytoplasm.

Disease relevance. Chromosomal recombination involving RPL7A activates the receptor kinase domain of the TRK oncogene.

Similarity. Belongs to the eukaryotic ribosomal protein eL8 family.

RefSeq proteins (1): NP_000963* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001921	Ribosomal_eL8_euk	Family
IPR004037	Ribosomal_eL8-like_CS	Conserved_site
IPR004038	Ribosomal_eL8/eL30/eS12/Gad45	Domain
IPR018492	Ribosomal_eL8/Nhp2	Family
IPR029064	Ribosomal_eL30-like_sf	Homologous_superfamily
IPR050257	eL8/uL1-like	Family

Pfam: PF01248

UniProt features (11 total): cross-link 7, modified residue 3, chain 1

Structure

Experimental structures (PDB)

200 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-P62424-F1	91.01	0.82

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 (10): 34, 245, 97, 217, 11, 20, 21, 48, 97, 125

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: 220 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, HORIUCHI_WTAP_TARGETS_DN, GRUETZMANN_PANCREATIC_CANCER_DN, MODULE_151, GCM_NPM1, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, KYNG_DNA_DAMAGE_DN, GOBP_MALE_GAMETE_GENERATION, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION

GO Biological Process (5): maturation of LSU-rRNA (GO:0000470), cytoplasmic translation (GO:0002181), translation (GO:0006412), RNA processing (GO:0006396), ribosome biogenesis (GO:0042254)

GO Molecular Function (4): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), ribosome (GO:0005840), focal adhesion (GO:0005925), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), 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
ribosome	2
intracellular membraneless organelle	2
rRNA processing	1
ribosomal large subunit biogenesis	1
translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
ribonucleoprotein complex biogenesis	1
nucleic acid binding	1
structural molecule activity	1
cell adhesion molecule binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
cell junction	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

359 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
XPC	CETN3	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
RPL7L1	RPL7A	psi-mi:“MI:0915”(physical association)	0.670
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
STAU1	RPL7A	psi-mi:“MI:0915”(physical association)	0.620
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPL36	RPL7A	psi-mi:“MI:0915”(physical association)	0.560
RPL7A	RSL1D1	psi-mi:“MI:0915”(physical association)	0.560
NOM1	RPLP0	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
MAK16	NVL	psi-mi:“MI:0914”(association)	0.530
KNOP1	DHX15	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
BHLHA15	RPLP0	psi-mi:“MI:0914”(association)	0.530

BioGRID (1126): RPL7A (Affinity Capture-MS), RPL7A (Affinity Capture-MS), RPL7A (Affinity Capture-MS), RPL7A (Affinity Capture-MS), RPL7A (Affinity Capture-MS), RPL7A (Affinity Capture-MS), RPL7A (Affinity Capture-MS), RPL7A (Affinity Capture-MS), RPL7A (Affinity Capture-MS), RPL7A (Affinity Capture-MS), DDX18 (Co-fractionation), EEF1A1 (Co-fractionation), PES1 (Co-fractionation), RPL10 (Co-fractionation), RPL10A (Co-fractionation)

ESM2 similar proteins: A0A1D8PF11, A3LSY0, A5DGV3, A6SIZ0, A6ZPY2, G1STW0, O13672, O57592, O65353, O76732, O97249, P0CR50, P0CR51, P0DJ14, P0DKK7, P12970, P15125, P15126, P17076, P29453, P32429, P35685, P46223, P47089, P48589, P49196, P49405, P49692, P62424, P62425, P80455, Q03253, Q04599, Q2TBQ5, Q4R5C2, Q54PX9, Q54XX3, Q54ZD1, Q5ADQ6, Q5ANA1

Diamond homologs: A0A1D8PF11, A0B601, A0RUB4, A2BK92, A3DMR6, A3MTA9, A4YIL9, A5UJN3, A6UT51, A8A912, A9A2Z3, B1Y9V4, B6YWH9, B8D6E8, B9LPY2, C3MJN1, C3MYY9, C3N038, C3N8Q2, C3NMR6, C4KJ77, C5A1V9, G1STW0, O13672, O26355, O29494, O57592, O76732, P0CQ52, P0CQ53, P0DJ14, P0DKK7, P12743, P12970, P17076, P29453, P32429, P35685, P46223, P49692

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL7A	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 224 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
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	16	12.6×	8e-11
Peptide chain elongation	14	11.9×	1e-09
DNA Damage Recognition in GG-NER	6	11.5×	5e-04
Eukaryotic Translation Termination	14	11.3×	2e-09
Response of EIF2AK4 (GCN2) to amino acid deficiency	15	11.2×	8e-10
Viral mRNA Translation	13	11.1×	1e-08
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	13	10.9×	1e-08
Nuclear events stimulated by ALK signaling in cancer	5	10.9×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	5	25.4×	3e-04
stress granule assembly	5	15.4×	3e-03
cytoplasmic translation	16	15.2×	9e-12
mRNA stabilization	7	13.2×	3e-04
ribosomal large subunit biogenesis	5	11.4×	8e-03
translational initiation	6	11.0×	3e-03
intrinsic apoptotic signaling pathway	6	11.0×	3e-03
rRNA processing	13	9.4×	5e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

918 predictions. Top by Δscore:

Variant	Effect	Δscore
9:133348920:A:AG	acceptor_gain	1.0000
9:133348921:G:GG	acceptor_gain	1.0000
9:133348921:GCC:G	acceptor_gain	1.0000
9:133348923:C:A	acceptor_gain	1.0000
9:133349023:GCC:G	donor_gain	1.0000
9:133349038:CATTG:C	donor_gain	1.0000
9:133349039:ATTG:A	donor_gain	1.0000
9:133349040:TTG:T	donor_gain	1.0000
9:133349040:TTGGT:T	donor_loss	1.0000
9:133349041:TG:T	donor_gain	1.0000
9:133349042:GG:G	donor_gain	1.0000
9:133349043:G:GG	donor_gain	1.0000
9:133349044:T:A	donor_loss	1.0000
9:133349547:TCA:T	acceptor_loss	1.0000
9:133349548:CA:C	acceptor_loss	1.0000
9:133349549:A:AG	acceptor_gain	1.0000
9:133349549:AG:A	acceptor_gain	1.0000
9:133349550:G:GT	acceptor_gain	1.0000
9:133349550:GG:G	acceptor_gain	1.0000
9:133349550:GGACA:G	acceptor_gain	1.0000
9:133349697:ACAG:A	donor_loss	1.0000
9:133349698:CAGG:C	donor_loss	1.0000
9:133349699:AG:A	donor_loss	1.0000
9:133349700:GG:G	donor_loss	1.0000
9:133349910:A:AG	acceptor_gain	1.0000
9:133349911:G:GT	acceptor_gain	1.0000
9:133349911:GC:G	acceptor_gain	1.0000
9:133349911:GCT:G	acceptor_gain	1.0000
9:133349911:GCTA:G	acceptor_gain	1.0000
9:133350048:AGCAG:A	donor_gain	1.0000

AlphaMissense

1708 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:133349551:G:A	G42E	1.000
9:133349586:T:C	F54L	1.000
9:133349588:T:A	F54L	1.000
9:133349588:T:G	F54L	1.000
9:133349595:T:A	W57R	1.000
9:133349595:T:C	W57R	1.000
9:133349597:G:C	W57C	1.000
9:133349597:G:T	W57C	1.000
9:133349673:T:C	F83L	1.000
9:133349674:T:C	F83S	1.000
9:133349675:C:A	F83L	1.000
9:133349675:C:G	F83L	1.000
9:133350606:T:C	F169L	1.000
9:133350608:C:A	F169L	1.000
9:133350608:C:G	F169L	1.000
9:133350622:G:A	C174Y	1.000
9:133350623:T:G	C174W	1.000
9:133350647:C:G	C182W	1.000
9:133350672:G:A	G191R	1.000
9:133350672:G:C	G191R	1.000
9:133350673:G:A	G191E	1.000
9:133351274:T:A	W237R	1.000
9:133351274:T:C	W237R	1.000
9:133351292:G:C	G243R	1.000
9:133349033:T:C	F39L	0.999
9:133349035:T:A	F39L	0.999
9:133349035:T:G	F39L	0.999
9:133349042:G:A	G42R	0.999
9:133349042:G:C	G42R	0.999
9:133349551:G:T	G42V	0.999

dbSNP variants (sampled 300 via entrez): RS1000171207 (9:133346889 G>T), RS1000288609 (9:133350957 A>G), RS1000438055 (9:133347855 A>C,T), RS1000861174 (9:133347994 C>T), RS1001079473 (9:133347738 C>A), RS1001525942 (9:133351289 C>T), RS1002249886 (9:133348033 TC>T), RS1002764919 (9:133349121 T>C), RS1003519686 (9:133348740 G>C), RS1004043288 (9:133347669 G>A), RS1004175758 (9:133350784 A>G), RS1004920762 (9:133351556 A>G), RS1005338436 (9:133347438 C>G,T), RS1006039846 (9:133349266 C>A,T), RS1006127023 (9:133348487 C>G,T)

Disease associations

OMIM: gene MIM:185640 | 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
GCST010725_19	Malaria	9.000000e-11
GCST010725_31	Malaria	9.000000e-21
GCST010725_98	Malaria	1.000000e-19

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067558 (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

50 potent at pChembl≥5 of 54 total, top 49 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
5.59	Kd	2569	nM	CHEMBL3752910
5.59	ED50	2569	nM	CHEMBL3752910
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
5.01	Kd	9779	nM	CHEMBL5653589
5.01	ED50	9779	nM	CHEMBL5653589

PubChem BioAssay actives

48 with measured affinity, of 209 total; 28 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149274: Binding affinity to human RPL7A incubated for 45 mins by Kinobead based pull down assay	kd	2.5687	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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149274: Binding affinity to human RPL7A incubated for 45 mins by Kinobead based pull down assay	kd	9.7786	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
sodium arsenite	decreases expression, increases activity, affects cotreatment, increases abundance, increases expression	3
perfluorooctanoic acid	decreases expression, increases expression	2
Cadmium	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	increases reaction, affects binding	1
sulforaphane	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
ochratoxin A	increases expression	1
phenanthrene	decreases expression	1
perfluorodecanoic acid	decreases expression	1
epigallocatechin gallate	increases expression	1
4-phenylbutyric acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
abrine	decreases 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.