RPL21

Summary

RPL21 (ribosomal protein L21, HGNC:10313) is a protein-coding gene on chromosome 13q12.2, encoding Large ribosomal subunit protein eL21 (P46778). Component of the large 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 60S subunit. The protein belongs to the L21E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6144 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypotrichosis 12 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 33 total — 1 pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_000982

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10313
Approved symbol	RPL21
Name	ribosomal protein L21
Location	13q12.2
Locus type	gene with protein product
Status	Approved
Aliases	L21, FLJ27458, MGC71252, MGC104274, MGC104275, DKFZp686C06101, eL21
Ensembl gene	ENSG00000122026
Ensembl biotype	protein_coding
OMIM	603636
Entrez	6144

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 14 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000272274, ENST00000311549, ENST00000319826, ENST00000326092, ENST00000461690, ENST00000466550, ENST00000473558, ENST00000483765, ENST00000485756, ENST00000493317, ENST00000907071, ENST00000907072, ENST00000939429, ENST00000939430, ENST00000939431, ENST00000939432, ENST00000939433, ENST00000939434, ENST00000939435

RefSeq mRNA: 1 — MANE Select: NM_000982 NM_000982

CCDS: CCDS9320

Canonical transcript exons

ENST00000311549 — 6 exons

Exon	Start	End
ENSE00001222524	27256436	27256568
ENSE00001830734	27251558	27251585
ENSE00003492826	27256184	27256334
ENSE00003545702	27254220	27254281
ENSE00003607298	27253765	27253843
ENSE00003688877	27255242	27255354

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.1144 / max 541.1070, expressed in 1820 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134511	15.9901	1794
134508	14.5840	1788
134510	5.7124	1666
134509	0.8843	460
111713	0.3784	162
134513	0.3277	152
134512	0.2375	85

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.88	gold quality
embryo	UBERON:0000922	99.84	gold quality
ganglionic eminence	UBERON:0004023	99.84	gold quality
colonic epithelium	UBERON:0000397	99.83	gold quality
primary visual cortex	UBERON:0002436	99.83	gold quality
endometrium	UBERON:0001295	99.82	gold quality
cortical plate	UBERON:0005343	99.82	gold quality
lymph node	UBERON:0000029	99.81	gold quality
ventricular zone	UBERON:0003053	99.80	gold quality
monocyte	CL:0000576	99.78	gold quality
leukocyte	CL:0000738	99.78	gold quality
ovary	UBERON:0000992	99.78	gold quality
superior frontal gyrus	UBERON:0002661	99.78	gold quality
left ovary	UBERON:0002119	99.77	gold quality
islet of Langerhans	UBERON:0000006	99.76	gold quality
uterus	UBERON:0000995	99.75	gold quality
bone marrow	UBERON:0002371	99.75	gold quality
right ovary	UBERON:0002118	99.74	gold quality
tonsil	UBERON:0002372	99.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.74	gold quality
body of pancreas	UBERON:0001150	99.73	gold quality
pancreas	UBERON:0001264	99.73	gold quality
granulocyte	CL:0000094	99.72	gold quality
bone marrow cell	CL:0002092	99.72	gold quality
endocervix	UBERON:0000458	99.72	gold quality
cortex of kidney	UBERON:0001225	99.72	gold quality
mammary gland	UBERON:0001911	99.72	gold quality
fallopian tube	UBERON:0003889	99.72	gold quality
thoracic mammary gland	UBERON:0005200	99.72	gold quality
body of uterus	UBERON:0009853	99.72	gold quality

Single-cell (SCXA)

Detected in 47 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	11806.82
E-HCAD-9	yes	10464.16
E-CURD-46	yes	10081.12
E-MTAB-8142	yes	8398.85
E-ENAD-17	yes	3839.27
E-CURD-122	yes	99.21
E-MTAB-9221	yes	56.10
E-MTAB-6678	yes	44.54
E-CURD-112	yes	32.99
E-MTAB-9067	yes	25.61
E-MTAB-10042	yes	14.83
E-GEOD-135922	yes	13.83
E-HCAD-35	yes	9.75
E-GEOD-137537	yes	5.98
E-HCAD-25	yes	4.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 2)

• The cause of hereditary hypotrichosis in this family was identified as a c.95G>A (p.Arg32Gln) mutation in the ribosomal protein L21. (PMID:21412954)
• The ribosomal protein eL21 interacts with the protein lysine methyltransferase SMYD2 and regulates its steady state levels. (PMID:34147559)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl21	ENSDARG00000010516
rattus_norvegicus	AABR07043626.1	ENSRNOG00000033487
drosophila_melanogaster	RpL21	FBGN0032987
caenorhabditis_elegans		WBGENE00004433

Protein

Protein identifiers

Large ribosomal subunit protein eL21 — P46778 (reviewed: P46778)

Alternative names: 60S ribosomal protein L21

All UniProt accessions (5): G3V1B3, P46778, M0R181, M0R3I5, Q6IAX2

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.

Subcellular location. Cytoplasm. Cytosol. Endoplasmic reticulum.

Disease relevance. Hypotrichosis 12 (HYPT12) [MIM:615885] A form of hypotrichosis, a condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The extent of scalp and body hair involvement can be very variable, within as well as between families. HYPT12 patients have normal scalp hair density at birth. Hair loss begins during the first 6 months of life and gradually progresses to nearly complete loss of scalp hair. The remaining hairs grow slowly and are thin, sparse, dry, and fragile. Body hair, axillary and pubic hair, eyebrows and eyelashes are also sparse or absent. HYPT12 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the eukaryotic ribosomal protein eL21 family.

RefSeq proteins (1): NP_000973* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001147	Ribosomal_eL21	Family
IPR008991	Translation_prot_SH3-like_sf	Homologous_superfamily
IPR018259	Ribosomal_eL21_CS	Conserved_site
IPR036948	Ribosomal_eL21_sf	Homologous_superfamily

Pfam: PF01157

UniProt features (14 total): sequence conflict 7, compositionally biased region 2, sequence variant 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

194 structures, top 30 by resolution.

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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46778-F1	94.12	0.91

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: 0 (showing top):

GO Biological Process (2): 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 (9): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), synapse (GO:0045202), ribosome (GO:0005840), 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
cytoplasm	2
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
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
cell junction	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

3416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL21	RPL28	P46779	959
RPL21	RPS9	P46781	953
RPL21	RPL27A	P46776	952
RPL21	RPS29	P30054	950
RPL21	RPL5	P46777	947
RPL21	RPS5	P46782	947
RPL21	RPS10	P46783	942
RPL21	RPS3A	P33443	867
RPL21	RPL9	P32969	803
RPL21	RPS24	P16632	795
RPL21	RPS4X	P12631	792
RPL21	RPS2	P15880	780
RPL21	RPS26	P02383	776
RPL21	RPL11	P25121	769
RPL21	RPL14	P50914	769

IntAct

203 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
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
ZC3HAV1	KHNYN	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
UBE3A	HERC2	psi-mi:“MI:0914”(association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PPP2R2B	DDX3X	psi-mi:“MI:0914”(association)	0.460
ESR1		psi-mi:“MI:0914”(association)	0.460
CENPE	RPL21	psi-mi:“MI:0915”(physical association)	0.400
DLG5	RPL21	psi-mi:“MI:0915”(physical association)	0.400
CAVIN1	RPL21	psi-mi:“MI:0915”(physical association)	0.400
DNAH6	RPL21	psi-mi:“MI:0915”(physical association)	0.400
SAXO4	RPL21	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (543): RPL21 (Affinity Capture-MS), RPL21 (Affinity Capture-MS), RPL21 (Affinity Capture-MS), RPL21 (Affinity Capture-MS), RPL10 (Co-fractionation), RPL10A (Co-fractionation), RPL11 (Co-fractionation), RPL12 (Co-fractionation), RPL13 (Co-fractionation), RPL13A (Co-fractionation), RPL15 (Co-fractionation), RPL18 (Co-fractionation), RPL18A (Co-fractionation), RPL21 (Co-fractionation), RPL21 (Co-fractionation)

ESM2 similar proteins: A0A324, A1XQR9, A4FUI2, A5JSS2, A6MZM2, G1SHQ2, O09167, O14602, O35900, O60739, P20280, P25800, P41567, P46778, P47813, P48024, P49666, P51971, P61220, P62303, P62304, P62305, P62308, P62309, Q09028, Q0D5W6, Q0P5B3, Q2KIA3, Q3B8H4, Q3ZBL0, Q4R4X9, Q503U0, Q5E938, Q5RA42, Q5RBW7, Q5RFF4, Q60872, Q60972, Q6GVM3, Q6QN05

Diamond homologs: A0A1D8PGY0, A0B7V4, A2STS6, A3CWY7, A3DML6, A4G096, A4YCT6, A5JSS2, A5UN04, A6UR83, A6UT27, A6VI82, A7I9H8, A8AAK8, A9A8J8, B1L7A8, B8GEV3, C3MQ30, C3MVE8, C3N5P7, C3NEB3, C3NHD9, C4KHC6, G1SHQ2, O09167, O27378, O42706, O82574, P20280, P34334, P38653, P46778, P49628, P49666, P49667, P54013, P58077, Q02753, Q12672, Q12XH4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL21	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 204 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
SRP-dependent cotranslational protein targeting to membrane	17	11.2×	1e-10
GTP hydrolysis and joining of the 60S ribosomal subunit	16	10.5×	8e-10
Formation of a pool of free 40S subunits	14	10.3×	9e-09
Eukaryotic Translation Termination	13	10.3×	4e-08
SARS-CoV-1 modulates host translation machinery	5	10.2×	4e-03
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	13	10.1×	4e-08
Peptide chain elongation	12	10.0×	2e-07
Viral mRNA Translation	12	10.0×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
stress granule assembly	5	16.8×	1e-03
cytoplasmic translation	15	15.5×	5e-11
liver regeneration	5	14.3×	2e-03
translational initiation	7	14.0×	2e-04
autophagosome maturation	6	11.8×	1e-03
negative regulation of translation	10	10.9×	1e-05
mitophagy	6	10.7×	2e-03
mRNA stabilization	5	10.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	12
Likely benign	7
Benign	13

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
139638	NM_000982.4(RPL21):c.95G>A (p.Arg32Gln)	Pathogenic

SpliceAI

653 predictions. Top by Δscore:

Variant	Effect	Δscore
13:27253756:T:TA	acceptor_gain	1.0000
13:27253763:A:AG	acceptor_gain	1.0000
13:27253764:G:GA	acceptor_gain	1.0000
13:27253764:GT:G	acceptor_gain	1.0000
13:27253764:GTA:G	acceptor_gain	1.0000
13:27253839:ACATG:A	donor_gain	1.0000
13:27253840:CATG:C	donor_gain	1.0000
13:27255240:A:AG	acceptor_gain	1.0000
13:27255240:AG:A	acceptor_gain	1.0000
13:27255241:G:GG	acceptor_gain	1.0000
13:27255241:GG:G	acceptor_gain	1.0000
13:27255241:GGGA:G	acceptor_gain	1.0000
13:27255350:GTTAA:G	donor_gain	1.0000
13:27255351:T:G	donor_gain	1.0000
13:27255355:G:GG	donor_gain	1.0000
13:27256178:GTCCA:G	acceptor_loss	1.0000
13:27256182:A:AG	acceptor_gain	1.0000
13:27256182:AG:A	acceptor_gain	1.0000
13:27256182:AGG:A	acceptor_gain	1.0000
13:27256183:G:GG	acceptor_gain	1.0000
13:27256183:GG:G	acceptor_gain	1.0000
13:27256183:GGG:G	acceptor_gain	1.0000
13:27256335:GT:G	donor_loss	1.0000
13:27256434:A:AG	acceptor_gain	1.0000
13:27256435:G:GG	acceptor_gain	1.0000
13:27256435:GCCT:G	acceptor_gain	1.0000
13:27253759:TTTCA:T	acceptor_loss	0.9900
13:27253760:TTCA:T	acceptor_loss	0.9900
13:27253761:TCAG:T	acceptor_loss	0.9900
13:27253762:CA:C	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001201636 (13:27252738 G>A,T), RS1001652937 (13:27253070 G>C), RS1002343812 (13:27256347 T>C,G), RS1002384259 (13:27255960 C>G,T), RS1002442751 (13:27251315 G>A), RS1003276962 (13:27253906 A>C,G), RS1003304042 (13:27254845 T>G), RS1003310261 (13:27250588 T>A,C), RS1003903255 (13:27250395 T>C), RS1003995138 (13:27253630 A>G,T), RS1004214402 (13:27252217 A>G), RS1004361553 (13:27253938 G>T), RS1004547799 (13:27253240 C>T), RS1004580383 (13:27253085 A>G), RS1004997531 (13:27252397 C>T)

Disease associations

OMIM: gene MIM:603636 | disease phenotypes: MIM:615885

GenCC curated gene-disease

Disease	Classification	Inheritance
hypotrichosis 12	Strong	Autosomal dominant
hypotrichosis simplex	Supportive	Autosomal dominant

Mondo (2): hypotrichosis 12 (MONDO:0014384), hypotrichosis simplex (MONDO:0018914)

Orphanet (1): Hypotrichosis simplex (Orphanet:55654)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000164	Abnormality of the dentition
HP:0000653	Sparse eyelashes
HP:0000951	Abnormality of the skin
HP:0000971	Abnormal sweat gland morphology
HP:0001596	Alopecia
HP:0001597	Abnormal nail morphology
HP:0002209	Sparse scalp hair
HP:0002215	Sparse axillary hair
HP:0002217	Slow-growing hair
HP:0002225	Sparse pubic hair
HP:0002231	Sparse body hair
HP:0003593	Infantile onset
HP:0008070	Sparse hair
HP:0011359	Dry hair
HP:0045075	Sparse eyebrow
HP:0100840	Aplasia/Hypoplasia of the eyebrow
HP:0200102	Sparse or absent eyelashes

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000111_1	Electrocardiographic traits	8.000000e-06
GCST008747_109	Estimated glomerular filtration rate	7.000000e-07
GCST90011899_153	Aspartate aminotransferase levels	7.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography
EFO:0004682	QT interval
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537160	Hypotrichosis simplex (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066895 (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
5.78	Kd	1643	nM	CHEMBL3752910
5.78	ED50	1643	nM	CHEMBL3752910
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
5.00	Kd	9953	nM	CHEMBL5653589
5.00	ED50	9953	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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149251: Binding affinity to human RPL21 incubated for 45 mins by Kinobead based pull down assay	kd	1.6429	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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149251: Binding affinity to human RPL21 incubated for 45 mins by Kinobead based pull down assay	kd	9.9532	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, affects cotreatment	5
sodium arsenite	decreases expression, increases activity, increases abundance, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
deoxynivalenol	increases expression	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
methylparaben	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
4-hydroxy-equilenin	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
chloropicrin	affects expression	1
calfactant	affects cotreatment, 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
bisphenol B	increases expression	1
abrine	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	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)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03492866	PHASE2	UNKNOWN	Efficacy of Topical Gentamycin for Hereditary Hypotrichosis Simplex Caused by Nonsense Mutations in CDSN