RPS21

Summary

RPS21 (ribosomal protein S21, HGNC:10409) is a protein-coding gene on chromosome 20q13.33, encoding Small ribosomal subunit protein eS21 (P63220). Component of the small ribosomal subunit. It is a common-essential gene (DepMap: required in 97.9% 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 S21E family of ribosomal proteins. It is located in the cytoplasm. Alternative splice variants that encode different protein isoforms have been described, but their existence has not been verified. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6227 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 18 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_001024

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10409
Approved symbol	RPS21
Name	ribosomal protein S21
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	S21, eS21
Ensembl gene	ENSG00000171858
Ensembl biotype	protein_coding
OMIM	180477
Entrez	6227

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 28 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000343986, ENST00000370562, ENST00000370592, ENST00000450116, ENST00000492356, ENST00000863379, ENST00000863380, ENST00000863381, ENST00000934820, ENST00000934821, ENST00000934822, ENST00000934823, ENST00000934824, ENST00000934825, ENST00000934826, ENST00000934827, ENST00000934828, ENST00000934829, ENST00000934830, ENST00000934831, ENST00000934832, ENST00000934833, ENST00000934834, ENST00000934835, ENST00000934836, ENST00000934837, ENST00000934838, ENST00000934839, ENST00000955608

RefSeq mRNA: 1 — MANE Select: NM_001024 NM_001024

CCDS: CCDS13497

Canonical transcript exons

ENST00000343986 — 6 exons

Exon	Start	End
ENSE00001348465	62388309	62388364
ENSE00001385371	62388457	62388520
ENSE00001453097	62387103	62387136
ENSE00003498663	62387611	62387674
ENSE00003520285	62387321	62387388
ENSE00003691811	62387843	62387914

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 938.7208 / max 6822.3545, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185727	884.3486	1828
185726	54.3722	1818

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	99.94	gold quality
penis	UBERON:0000989	99.93	gold quality
trabecular bone tissue	UBERON:0002483	99.92	gold quality
middle frontal gyrus	UBERON:0002702	99.92	gold quality
superficial temporal artery	UBERON:0001614	99.91	gold quality
mammalian vulva	UBERON:0000997	99.90	gold quality
thymus	UBERON:0002370	99.90	gold quality
caput epididymis	UBERON:0004358	99.90	gold quality
paraflocculus	UBERON:0005351	99.90	gold quality
urethra	UBERON:0000057	99.89	gold quality
oral cavity	UBERON:0000167	99.89	gold quality
skin of hip	UBERON:0001554	99.89	gold quality
mammary duct	UBERON:0001765	99.89	gold quality
upper leg skin	UBERON:0004262	99.89	gold quality
epithelium of mammary gland	UBERON:0003244	99.88	gold quality
endometrium epithelium	UBERON:0004811	99.88	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.88	gold quality
colonic mucosa	UBERON:0000317	99.87	gold quality
seminal vesicle	UBERON:0000998	99.87	gold quality
germinal epithelium of ovary	UBERON:0001304	99.87	gold quality
trachea	UBERON:0003126	99.87	gold quality
upper arm skin	UBERON:0004263	99.87	gold quality
corpus epididymis	UBERON:0004359	99.87	gold quality
superior surface of tongue	UBERON:0007371	99.87	gold quality
endothelial cell	CL:0000115	99.85	gold quality
left ovary	UBERON:0002119	99.85	gold quality
synovial joint	UBERON:0002217	99.85	gold quality
cartilage tissue	UBERON:0002418	99.85	gold quality
cauda epididymis	UBERON:0004360	99.85	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6308	yes	8107.97
E-MTAB-8410	yes	7832.39
E-MTAB-9221	yes	5324.30
E-CURD-122	yes	5182.27
E-CURD-88	yes	4562.30
E-MTAB-6701	yes	4302.42
E-GEOD-135922	yes	4004.31
E-CURD-98	yes	3275.73
E-CURD-46	yes	52.07
E-CURD-112	yes	38.99
E-HCAD-9	yes	27.14
E-MTAB-10042	yes	16.29
E-MTAB-7316	yes	14.55
E-HCAD-35	yes	8.41
E-GEOD-137537	yes	5.94

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• HLDF protein and anti-HLDF antibodies are involved in blood pressure regulation and can be considered as biomarkers for early diagnosis of hypertension and its cerebral complications. (PMID:23113252)
• Specific effects of HLDF+PA were manifested as an increase in the production of IL-8, IL-17, and GM-CSF due to suppression of Th1-dependent immune reactions in a Th17-mediated mechanism that is a part of a broader functional antagonism of Th1 and Th17 lymphocyte subpopulations. (PMID:27595831)
• The results show that RPS19, RPS21 or RPS24 are upregulated in malignant tissue and may serve as putative biomarkers for prostate cancer. (PMID:29016636)
• Serum Level of HLDF24 Peptide as an Objective Marker of Prehypertension. (PMID:31938910)
• HNF1A regulates oxaliplatin resistance in pancreatic cancer by targeting 53BP1. (PMID:36825600)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps21	ENSDARG00000025850
mus_musculus	Rps21	ENSMUSG00000039001
rattus_norvegicus	LOC100359505	ENSRNOG00000032807
rattus_norvegicus	Rps21-ps1	ENSRNOG00000033916
rattus_norvegicus	Rps21	ENSRNOG00000060449
drosophila_melanogaster	RpS21	FBGN0015521
caenorhabditis_elegans		WBGENE00004490

Protein

Protein identifiers

Small ribosomal subunit protein eS21 — P63220 (reviewed: P63220)

Alternative names: 40S ribosomal protein S21

All UniProt accessions (5): P63220, Q6FGH5, Q8WVC2, Q9BYK1, Q9BYK2

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.

Subunit / interactions. Component of the 40S small ribosomal subunit.

Subcellular location. Cytoplasm. Cytosol. Rough endoplasmic reticulum.

Similarity. Belongs to the eukaryotic ribosomal protein eS21 family.

RefSeq proteins (1): NP_001015* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001931	Ribosomal_eS21	Family
IPR018279	Ribosomal_eS21_CS	Conserved_site
IPR038579	Ribosomal_eS21_sf	Homologous_superfamily

Pfam: PF01249

UniProt features (13 total): strand 4, turn 3, modified residue 2, helix 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

209 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-P63220-F1	95.37	0.97

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 (3): 1, 81, 41

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: 192 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_MATURATION_OF_SSU_RRNA, HSIAO_HOUSEKEEPING_GENES, GOBP_TRANSLATION, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, MARTINEZ_RB1_TARGETS_DN, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GNF2_FBL

GO Biological Process (4): endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000447), endonucleolytic cleavage to generate mature 3’-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000461), cytoplasmic translation (GO:0002181), translation (GO:0006412)

GO Molecular Function (3): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (11): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), rough endoplasmic reticulum (GO:0005791), cytosol (GO:0005829), small ribosomal subunit (GO:0015935), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), synapse (GO:0045202), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

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	3
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	2
endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	2
ribosome	2
cytoplasm	2
maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1
rRNA 3’-end processing	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
nucleic acid binding	1
structural molecule activity	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
ribosomal subunit	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1
cell junction	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

124 interactions, top by confidence:

A	B	Type	Score
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
ZNF76	RPS21	psi-mi:“MI:0915”(physical association)	0.560
RPS21	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
RPS21	FHL5	psi-mi:“MI:0915”(physical association)	0.560
RPSA	DKC1	psi-mi:“MI:0914”(association)	0.530
RPS11	RPS17	psi-mi:“MI:0403”(colocalization)	0.530
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
steC	SCD	psi-mi:“MI:0914”(association)	0.460
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
ABL1	RPLP1	psi-mi:“MI:0914”(association)	0.350
MAST3	PPP6C	psi-mi:“MI:0914”(association)	0.350
Eif3a	RPSA	psi-mi:“MI:0914”(association)	0.350
NPM1	RPSA	psi-mi:“MI:0914”(association)	0.350
Eif3e	RPSA	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
MAP2K3	SUPT5H	psi-mi:“MI:0914”(association)	0.350
DOK2	MYO1C	psi-mi:“MI:0914”(association)	0.350
RIPK1	TAF4	psi-mi:“MI:0914”(association)	0.350
PRKD1	MYO1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (377): ZUFSP (Two-hybrid), RPS21 (Affinity Capture-MS), RPS21 (Affinity Capture-MS), RPS21 (Affinity Capture-MS), RPS21 (Co-fractionation), RPS21 (Co-fractionation), RPS21 (Co-fractionation), RPS21 (Affinity Capture-MS), RPS21 (Affinity Capture-MS), RPS21 (Affinity Capture-MS), RPS21 (Affinity Capture-MS), RPS21 (Affinity Capture-MS), RPS21 (Affinity Capture-MS), RPS21 (Affinity Capture-MS), RPS21 (Affinity Capture-MS)

ESM2 similar proteins: A0A381, A4GGF5, A6MMG8, A9LYE6, B2LMN9, G1TG89, G1TM82, O63057, P05765, P34832, P62244, P62245, P62246, P62729, P62731, P62732, P63220, P63221, P82129, Q09MB7, Q1KXP8, Q27RZ0, Q2MI54, Q2MIE1, Q32PB8, Q332R9, Q33BY2, Q3BAH4, Q3C1M8, Q4VZK9, Q589A4, Q5R938, Q67ID1, Q6AZJ9, Q6DDC6, Q6EM56, Q6EM77, Q6EM90, Q6EVZ0, Q6KGX9

Diamond homologs: A0A1D8PCG7, B3MLA8, B3NA78, B4GSC0, B4I2S0, B4JZG4, B4KIE3, B4LQD3, B4N002, B4Q8M1, G1TM82, O76927, O93798, P05764, P05765, P0C0V8, P35687, P49197, P63220, P63221, Q29KF5, Q32PB8, Q3E754, Q3E902, Q41852, Q4GXP2, Q4GXP3, Q4KTC0, Q4PM64, Q4WI01, Q54BN4, Q612Q9, Q6AZJ9, Q6CXT6, Q6DDC6, Q6F477, Q6FMF8, Q6PUF8, Q6RF66, Q6XIR2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS21	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
SARS-CoV-1 modulates host translation machinery	7	24.6×	3e-07
Eukaryotic Translation Initiation	6	21.0×	7e-06
Cap-dependent Translation Initiation	6	21.0×	7e-06
Formation of the ternary complex, and subsequently, the 43S complex	8	19.6×	2e-07
Ribosomal scanning and start codon recognition	9	19.5×	2e-08
SRP-dependent cotranslational protein targeting to membrane	17	19.4×	5e-15
Eukaryotic Translation Elongation	6	19.0×	1e-05
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	6	18.5×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	15	25.2×	2e-14
translational initiation	5	16.3×	2e-03
rRNA processing	12	15.4×	5e-09
ribosomal small subunit biogenesis	7	14.5×	1e-04
translation	14	13.1×	1e-09
negative regulation of translation	6	10.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

426 predictions. Top by Δscore:

Variant	Effect	Δscore
20:62387384:AAATG:A	donor_gain	1.0000
20:62387385:AATG:A	donor_gain	1.0000
20:62387386:ATG:A	donor_gain	1.0000
20:62387387:TG:T	donor_gain	1.0000
20:62387387:TGG:T	donor_loss	1.0000
20:62387388:GG:G	donor_gain	1.0000
20:62387389:G:GG	donor_gain	1.0000
20:62387389:GT:G	donor_loss	1.0000
20:62387390:T:A	donor_loss	1.0000
20:62387609:A:AC	acceptor_loss	1.0000
20:62387609:A:AG	acceptor_gain	1.0000
20:62387610:G:GT	acceptor_gain	1.0000
20:62387610:GC:G	acceptor_gain	1.0000
20:62387610:GCT:G	acceptor_gain	1.0000
20:62387610:GCTC:G	acceptor_gain	1.0000
20:62387610:GCTCC:G	acceptor_gain	1.0000
20:62387672:GAG:G	donor_gain	1.0000
20:62387673:AGGT:A	donor_loss	1.0000
20:62387674:GGTGA:G	donor_loss	1.0000
20:62387675:G:A	donor_loss	1.0000
20:62387675:G:GG	donor_gain	1.0000
20:62387608:C:G	acceptor_gain	0.9900
20:62388306:AAG:A	acceptor_gain	0.9900
20:62388307:A:G	acceptor_gain	0.9900
20:62387673:AG:A	donor_gain	0.9800
20:62387674:GG:G	donor_gain	0.9800
20:62387837:TTCTA:T	acceptor_loss	0.9800
20:62387841:A:AT	acceptor_loss	0.9800
20:62387842:G:GC	acceptor_loss	0.9800
20:62387990:GTGCC:G	donor_gain	0.9800

AlphaMissense

549 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:62387898:G:T	G57V	1.000
20:62387366:G:C	D10H	0.999
20:62387367:A:T	D10V	0.999
20:62387370:T:C	L11P	0.999
20:62387372:T:C	Y12H	0.999
20:62387378:C:A	P14T	0.999
20:62387379:C:A	P14Q	0.999
20:62387386:A:C	K16N	0.999
20:62387386:A:T	K16N	0.999
20:62387387:T:C	C17R	0.999
20:62387618:A:C	S20R	0.999
20:62387619:G:T	S20I	0.999
20:62387620:C:A	S20R	0.999
20:62387620:C:G	S20R	0.999
20:62387625:G:C	R22P	0.999
20:62387631:T:A	I24N	0.999
20:62387642:G:C	D28H	0.999
20:62387643:A:T	D28V	0.999
20:62387652:C:A	S31Y	0.999
20:62387652:C:T	S31F	0.999
20:62387859:G:A	G44D	0.999
20:62387894:T:C	C56R	0.999
20:62387895:G:A	C56Y	0.999
20:62387896:C:G	C56W	0.999
20:62387897:G:A	G57R	0.999
20:62387897:G:C	G57R	0.999
20:62387897:G:T	G57W	0.999
20:62387898:G:A	G57E	0.999
20:62387906:C:A	R60S	0.999
20:62388309:G:C	G63R	0.999

dbSNP variants (sampled 300 via entrez): RS1000089780 (20:62386927 C>A), RS1000833913 (20:62385652 A>T), RS1000983455 (20:62385343 C>G), RS1002038455 (20:62385633 C>A), RS1002291159 (20:62388758 C>T), RS1002849670 (20:62387135 A>C,G), RS1004245899 (20:62388511 T>C,G), RS1004651321 (20:62385940 G>A,C), RS1004908302 (20:62386171 G>A,C), RS1005600113 (20:62387585 C>T), RS1006403939 (20:62386531 T>C), RS1006912338 (20:62387539 C>A,G,T), RS1007684040 (20:62386165 C>A), RS1008614443 (20:62385271 A>G), RS1008817738 (20:62388698 TAACTC>T)

Disease associations

OMIM: gene MIM:180477 | 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
GCST001942_4	Prostate cancer	4.000000e-08
GCST003799_11	Colorectal cancer	8.000000e-11
GCST007856_47	Colorectal cancer or advanced adenoma	1.000000e-26

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067552 (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
8.17	Kd	6.829	nM	CHEMBL5653589
8.17	ED50	6.829	nM	CHEMBL5653589
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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149295: Binding affinity to human RPS21 incubated for 45 mins by Kinobead based pull down assay	kd	0.0068	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, affects cotreatment	6
sodium arsenite	affects reaction, increases expression, decreases reaction, affects binding, decreases expression (+3 more)	5
Particulate Matter	decreases expression, increases expression	3
Smoke	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment, decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
perfluorooctanoic acid	decreases expression	1
phenanthrene	decreases expression	1
perfluorodecanoic acid	decreases expression	1
phenethyl isothiocyanate	affects binding	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
candoxin	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
MT19c compound	increases expression	1
capivasertib	decreases reaction, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	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.