RPS5

Summary

RPS5 (ribosomal protein S5, HGNC:10426) is a protein-coding gene on chromosome 19q13.43, encoding Small ribosomal subunit protein uS7 (P46782). Component of the small ribosomal subunit. It is a common-essential gene (DepMap: required in 99.7% 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 40S subunit. The protein belongs to the S7P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6193 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 25 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_001009

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10426
Approved symbol	RPS5
Name	ribosomal protein S5
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	S5, uS7
Ensembl gene	ENSG00000083845
Ensembl biotype	protein_coding
OMIM	603630
Entrez	6193

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 27 protein_coding, 3 retained_intron

ENST00000196551, ENST00000596046, ENST00000596314, ENST00000598098, ENST00000598495, ENST00000598807, ENST00000599232, ENST00000599909, ENST00000601521, ENST00000851167, ENST00000851168, ENST00000851169, ENST00000851170, ENST00000851171, ENST00000851172, ENST00000851173, ENST00000851174, ENST00000912985, ENST00000912986, ENST00000912987, ENST00000912988, ENST00000912989, ENST00000912990, ENST00000912991, ENST00000912992, ENST00000912993, ENST00000912994, ENST00000912995, ENST00000951621, ENST00000951622

RefSeq mRNA: 1 — MANE Select: NM_001009 NM_001009

CCDS: CCDS12978

Canonical transcript exons

ENST00000196551 — 6 exons

Exon	Start	End
ENSE00001210481	58387269	58387339
ENSE00003587550	58388137	58388245
ENSE00003591758	58392976	58393185
ENSE00003891648	58394682	58394804
ENSE00003892253	58393359	58393487
ENSE00003894392	58394497	58394595

Expression profiles

Bgee: expression breadth ubiquitous, 306 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1076.8252 / max 8161.9636, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177838	1074.1013	1827
177839	1.4872	827
177840	1.2367	643

Top tissues by expression

306 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	99.87	gold quality
adult organism	UBERON:0007023	99.87	gold quality
mammalian vulva	UBERON:0000997	99.82	gold quality
trabecular bone tissue	UBERON:0002483	99.81	gold quality
upper arm skin	UBERON:0004263	99.81	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.81	gold quality
penis	UBERON:0000989	99.80	gold quality
left ovary	UBERON:0002119	99.80	gold quality
oral cavity	UBERON:0000167	99.79	gold quality
skin of leg	UBERON:0001511	99.79	gold quality
superficial temporal artery	UBERON:0001614	99.79	gold quality
right ovary	UBERON:0002118	99.79	gold quality
upper leg skin	UBERON:0004262	99.79	gold quality
right uterine tube	UBERON:0001302	99.78	gold quality
skin of abdomen	UBERON:0001416	99.78	gold quality
zone of skin	UBERON:0000014	99.77	gold quality
nipple	UBERON:0002030	99.77	gold quality
lower esophagus mucosa	UBERON:0035834	99.77	gold quality
body of pancreas	UBERON:0001150	99.76	gold quality
cartilage tissue	UBERON:0002418	99.76	gold quality
caput epididymis	UBERON:0004358	99.76	gold quality
colonic mucosa	UBERON:0000317	99.75	gold quality
endocervix	UBERON:0000458	99.75	gold quality
gingiva	UBERON:0001828	99.75	gold quality
gingival epithelium	UBERON:0001949	99.75	gold quality
thymus	UBERON:0002370	99.75	gold quality
endometrium epithelium	UBERON:0004811	99.75	gold quality
body of uterus	UBERON:0009853	99.75	gold quality
embryo	UBERON:0000922	99.74	gold quality
ovary	UBERON:0000992	99.74	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	3496.36
E-CURD-122	yes	93.86
E-CURD-46	yes	89.98
E-CURD-88	yes	65.45
E-MTAB-9221	yes	53.08
E-HCAD-11	yes	51.17
E-HCAD-13	yes	26.45
E-HCAD-9	yes	25.45
E-MTAB-10042	yes	15.90
E-MTAB-9543	yes	15.71
E-GEOD-135922	yes	11.39
E-MTAB-9067	yes	9.95
E-HCAD-35	yes	8.74
E-GEOD-130148	yes	7.36
E-MTAB-9801	yes	6.22

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• Transfected into yeast cells, plays an important role in maintaining the accuracy of translation. (PMID:17901157)
• Mutual effect of human ribosomal proteins S5 and S16 on their binding with 18S rRNA fragment 1203-1236/1521-1698 (PMID:19807034)
• Data indicate that beta hairpin structure present in ribosomal protein S5 (RPS5) is important for IRES-RPS5 interaction. (PMID:25712089)
• Stabilization of CDK6 by ribosomal protein uS7, a target protein of the natural product fucoxanthinol. (PMID:35681048)
• KDM4D enhances osteo/dentinogenic differentiation and migration of SCAPs via binding to RPS5. (PMID:36579641)
• Eukaryotic Ribosomal Protein S5 of the 40S Subunit: Structure and Function. (PMID:36834797)
• Unraveling the Role of RNA-Binding Proteins, with a Focus on RPS5, in the Malignant Progression of Hepatocellular Carcinoma. (PMID:38255847)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps5	ENSDARG00000043453
mus_musculus	Rps5	ENSMUSG00000012848
rattus_norvegicus	Rps5	ENSRNOG00000019453
drosophila_melanogaster	RpS5a	FBGN0002590
drosophila_melanogaster	RpS5b	FBGN0038277
caenorhabditis_elegans		WBGENE00004474

Paralogs (1): MRPS7 (ENSG00000125445)

Protein

Protein identifiers

Small ribosomal subunit protein uS7 — P46782 (reviewed: P46782)

Alternative names: 40S ribosomal protein S5

All UniProt accessions (4): P46782, M0QZN2, M0R0F0, M0R0R2

UniProt curated annotations — full annotation on UniProt →

Function. Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.

Subunit / interactions. Component of the small ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Similarity. Belongs to the universal ribosomal protein uS7 family.

RefSeq proteins (1): NP_001000* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000235	Ribosomal_uS7	Family
IPR005716	Ribosomal_uS7_euk/arc	Family
IPR020606	Ribosomal_uS7_CS	Conserved_site
IPR023798	Ribosomal_uS7_dom	Domain
IPR036823	Ribosomal_uS7_dom_sf	Homologous_superfamily

Pfam: PF00177

UniProt features (31 total): helix 10, strand 9, modified residue 5, chain 2, turn 2, initiator methionine 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

213 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8GLP	ELECTRON MICROSCOPY	1.67
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
7R4X	ELECTRON MICROSCOPY	2.15
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8YOP	ELECTRON MICROSCOPY	2.2
9O3V	ELECTRON MICROSCOPY	2.2
9O3Y	ELECTRON MICROSCOPY	2.2
8JDK	ELECTRON MICROSCOPY	2.26
8G5Y	ELECTRON MICROSCOPY	2.29
9S3D	ELECTRON MICROSCOPY	2.32
9RPV	ELECTRON MICROSCOPY	2.35
9S3B	ELECTRON MICROSCOPY	2.38
8K2C	ELECTRON MICROSCOPY	2.4
8XSX	ELECTRON MICROSCOPY	2.4
9SPF	ELECTRON MICROSCOPY	2.4
9SPI	ELECTRON MICROSCOPY	2.4
8JDL	ELECTRON MICROSCOPY	2.42
9S3C	ELECTRON MICROSCOPY	2.42
9QLO	ELECTRON MICROSCOPY	2.47
9P8B	ELECTRON MICROSCOPY	2.48
7XNY	ELECTRON MICROSCOPY	2.5
8JDJ	ELECTRON MICROSCOPY	2.5
9RUC	ELECTRON MICROSCOPY	2.5
8G60	ELECTRON MICROSCOPY	2.54
8IFE	ELECTRON MICROSCOPY	2.57
9P7D	ELECTRON MICROSCOPY	2.57

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46782-F1	90.56	0.79

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 (6): 1, 2, 14, 47, 142, 47

Function

Pathways and Gene Ontology

Reactome pathways

50 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-72649	Translation initiation complex formation
R-HSA-72689	Formation of a pool of free 40S subunits
R-HSA-72695	Formation of the ternary complex, and subsequently, the 43S complex
R-HSA-72702	Ribosomal scanning and start codon recognition
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-9735869	SARS-CoV-1 modulates host translation machinery
R-HSA-9754678	SARS-CoV-2 modulates host translation machinery
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-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
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-156842	Eukaryotic Translation Elongation
R-HSA-1643685	Disease
R-HSA-168255	Influenza Infection
R-HSA-168273	Influenza Viral RNA Transcription and Replication
R-HSA-2262752	Cellular responses to stress
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-376176	Signaling by ROBO receptors
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 251 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCM_NPM1, MORF_UBE2I, HSIAO_HOUSEKEEPING_GENES, GOBP_TRANSLATIONAL_INITIATION, PATIL_LIVER_CANCER, GOBP_TRANSLATION, GCM_PSME1, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, LUI_TARGETS_OF_PAX8_PPARG_FUSION, NRF2_01

GO Biological Process (5): cytoplasmic translation (GO:0002181), translation (GO:0006412), translational initiation (GO:0006413), regulation of translational fidelity (GO:0006450), ribosomal small subunit biogenesis (GO:0042274)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA binding (GO:0003729), structural constituent of ribosome (GO:0003735), rRNA binding (GO:0019843), protein binding (GO:0005515)

GO Cellular Component (15): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), ribosome (GO:0005840), focal adhesion (GO:0005925), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), small-subunit processome (GO:0032040), synapse (GO:0045202), extracellular exosome (GO:0070062), ribonucleoprotein complex (GO:1990904), nucleus (GO:0005634), nucleolus (GO:0005730), small ribosomal subunit (GO:0015935)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Translation	2
Nonsense-Mediated Decay (NMD)	2
Ribosome-associated quality control	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
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1
Signaling by ROBO receptors	1
Cellular response to starvation	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
translation	2
RNA binding	2
ribosome	2
nuclear lumen	2
intracellular membraneless organelle	2
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
formation of translation initiation ternary complex	1
metabolic process	1
regulation of biological quality	1
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
nucleic acid binding	1
structural molecule activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
cell junction	1
extracellular vesicle	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
ribosomal subunit	1

Protein interactions and networks

STRING

4837 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS5	RPS9	P46781	969
RPS5	RPS10	P46783	967
RPS5	RPL5	P46777	957
RPS5	RPL28	P46779	953
RPS5	RPL21	P46778	947
RPS5	RPS29	P30054	947
RPS5	RPL27A	P46776	928
RPS5	RPL11	P25121	878
RPS5	RPL8	P25120	809
RPS5	RPS19	P39019	804
RPS5	RPS3	P23396	800
RPS5	RPS2	P15880	796
RPS5	RPL9	P32969	787
RPS5	RPS16	P17008	774
RPS5	RPS20	P17075	768

IntAct

266 interactions, top by confidence:

A	B	Type	Score
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPS5	JPH3	psi-mi:“MI:0915”(physical association)	0.560
HTT	RPS5	psi-mi:“MI:0915”(physical association)	0.560
RPS5	ATXN1	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZCRB1	DKC1	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
THAP3	CASC3	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (699): RPS5 (Affinity Capture-MS), RPS5 (Affinity Capture-RNA), RPS5 (Affinity Capture-RNA), RPS5 (Affinity Capture-MS), RPS5 (Affinity Capture-MS), RPS5 (Affinity Capture-MS), RPS5 (Affinity Capture-MS), RPS5 (Affinity Capture-MS), CANX (Co-fractionation), CLGN (Co-fractionation), EEF1A1 (Co-fractionation), FBL (Co-fractionation), GFM2 (Co-fractionation), GNL3 (Co-fractionation), HBS1L (Co-fractionation)

ESM2 similar proteins: A0A1D8PK40, A9KD35, A9NAM0, B6J267, B6J5C8, D0VWQ5, G1TFM5, G1TYL6, O02639, O05639, O26129, O42699, O65055, P05734, P0CX82, P0CX83, P0DJ15, P0DJ60, P14024, P14329, P24050, P26784, P26785, P36241, P46782, P49693, P84098, P84099, P84100, P97461, Q04EH1, Q27389, Q3B6E3, Q3T0W9, Q5AB87, Q5E988, Q5RB99, Q6JWW5, Q6P5L3, Q6YPI5

Diamond homologs: A0B563, A0RUR1, A0T0K5, A0T0Z9, A1RSA1, A1TYJ3, A2STX0, A4FWF1, A4IJI5, A4XI35, A5IM79, A6UV45, A6VGV4, A7I4X5, A8MBL5, A9A9U5, B0R8D0, B1L735, B1LBP4, B1WQY6, B1YC67, B3EUF4, B5YDT9, B6YT21, B7GJ63, B8D6G4, B8E1C9, B8HVR9, B9K882, B9KZZ1, B9MQG9, C5A203, C5D3R3, G1TFM5, O14277, O15587, O24111, O27130, O28386, O59230

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MPHOSPH10	“up-regulates activity”	RPS5	binding
RPS5	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 200 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
Eukaryotic Translation Initiation	14	30.9×	1e-16
Cap-dependent Translation Initiation	14	30.9×	1e-16
SARS-CoV-1 modulates host translation machinery	14	30.9×	1e-16
Eukaryotic Translation Elongation	14	27.9×	7e-16
Formation of the ternary complex, and subsequently, the 43S complex	18	27.7×	3e-20
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	14	27.2×	1e-15
Nonsense-Mediated Decay (NMD)	16	26.6×	1e-17
Translation initiation complex formation	18	24.5×	3e-19

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	6	38.1×	1e-06
chromosome condensation	6	28.6×	6e-06
cytoplasmic translation	27	28.2×	3e-29
ribosomal small subunit biogenesis	15	19.3×	4e-13
stress granule assembly	5	17.0×	1e-03
translational initiation	8	16.2×	4e-06
ribosomal large subunit biogenesis	6	15.0×	3e-04
translation	25	14.5×	2e-19

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

893 predictions. Top by Δscore:

Variant	Effect	Δscore
19:58380939:A:AC	donor_gain	1.0000
19:58380940:C:CC	donor_gain	1.0000
19:58380940:CT:C	donor_gain	1.0000
19:58380940:CTCT:C	donor_gain	1.0000
19:58388118:T:TA	acceptor_gain	1.0000
19:58388122:A:AG	acceptor_gain	1.0000
19:58388123:T:G	acceptor_gain	1.0000
19:58388125:A:AG	acceptor_gain	1.0000
19:58388125:ACCCT:A	acceptor_gain	1.0000
19:58388126:C:G	acceptor_gain	1.0000
19:58388129:T:A	acceptor_gain	1.0000
19:58388132:CCCA:C	acceptor_loss	1.0000
19:58388133:CCAG:C	acceptor_loss	1.0000
19:58388134:CAGG:C	acceptor_loss	1.0000
19:58388135:A:AC	acceptor_loss	1.0000
19:58388135:A:AG	acceptor_gain	1.0000
19:58388135:AG:A	acceptor_gain	1.0000
19:58388136:G:GG	acceptor_gain	1.0000
19:58388136:GG:G	acceptor_gain	1.0000
19:58388136:GGA:G	acceptor_gain	1.0000
19:58388136:GGAT:G	acceptor_gain	1.0000
19:58388241:TGCAG:T	donor_loss	1.0000
19:58388242:GCAGG:G	donor_loss	1.0000
19:58388243:CAG:C	donor_loss	1.0000
19:58388244:AGGT:A	donor_loss	1.0000
19:58388245:GG:G	donor_loss	1.0000
19:58388246:G:C	donor_loss	1.0000
19:58388247:T:G	donor_loss	1.0000
19:58392958:T:TA	acceptor_gain	1.0000
19:58392965:T:A	acceptor_gain	1.0000

AlphaMissense

1335 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:58388204:T:A	W23R	1.000
19:58388204:T:C	W23R	1.000
19:58393048:T:C	F61L	1.000
19:58393049:T:C	F61S	1.000
19:58393050:C:A	F61L	1.000
19:58393050:C:G	F61L	1.000
19:58393063:T:C	C66R	1.000
19:58393065:T:G	C66W	1.000
19:58393078:C:A	R71S	1.000
19:58393082:T:C	L72P	1.000
19:58393106:G:T	G80V	1.000
19:58393118:G:A	G84D	1.000
19:58393118:G:T	G84V	1.000
19:58393153:G:C	A96P	1.000
19:58393166:T:A	I100K	1.000
19:58393172:T:C	L102P	1.000
19:58393383:G:C	A115P	1.000
19:58393395:A:C	S119R	1.000
19:58393397:T:A	S119R	1.000
19:58393397:T:G	S119R	1.000
19:58393398:G:C	G120R	1.000
19:58393399:G:A	G120D	1.000
19:58393402:C:A	P121H	1.000
19:58393407:G:A	E123K	1.000
19:58393408:A:T	E123V	1.000
19:58393410:G:C	D124H	1.000
19:58393411:A:T	D124V	1.000
19:58393414:C:T	S125F	1.000
19:58393423:T:A	I128N	1.000
19:58393425:G:A	G129R	1.000

dbSNP variants (sampled 300 via entrez): RS1000196076 (19:58393814 T>C), RS1000405423 (19:58386928 G>A), RS1000458424 (19:58391341 A>G), RS1000894230 (19:58387315 A>C,G), RS1000945998 (19:58387484 C>T), RS1001000828 (19:58387714 C>G,T), RS1001243338 (19:58392696 C>T), RS1001321590 (19:58389856 C>T), RS1001340920 (19:58385949 G>A), RS1002127803 (19:58390097 A>G), RS1002823607 (19:58387752 A>C,G), RS1003172068 (19:58389082 A>C,G), RS1003530662 (19:58389090 T>G), RS1003689654 (19:58394246 C>G), RS1004043857 (19:58394052 C>T)

Disease associations

OMIM: gene MIM:603630 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90006994_10	Gut microbiota relative abundance (Ruminococcus belonging to family Erysipelotrichaceae)	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066892 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

51 potent at pChembl≥5 of 55 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	Kd	50.07	nM	CHEMBL5653589
7.30	ED50	50.07	nM	CHEMBL5653589
6.75	Kd	176.4	nM	CHEMBL3752910
6.75	ED50	176.4	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
5.26	Kd	5463	nM	MOLIBRESIB
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

49 with measured affinity, of 216 total; 29 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149308: Binding affinity to human RPS5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0501	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149308: Binding affinity to human RPS5 incubated for 45 mins by Kinobead based pull down assay	kd	0.1764	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-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179085: Binding affinity against RPS5 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	5.4630	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	decreases expression, increases activity, increases abundance, increases expression	3
perfluorooctane sulfonic acid	increases expression	2
Arsenic	decreases expression, increases abundance, increases expression	2
Cisplatin	increases expression, affects expression, affects reaction	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
beta-lapachone	increases expression	1
arsenite	increases reaction, affects binding	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
cupric oxide	increases expression	1
artenimol	affects binding	1
arsenic trichloride	decreases expression, increases abundance	1
azoxystrobin	increases expression	1
chloropicrin	affects expression	1
deguelin	increases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	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
pyrimidifen	increases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
pyrachlostrobin	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1

ChEMBL screening assays

97 unique, capped per target: 97 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.