RPL11

Summary

RPL11 (ribosomal protein L11, HGNC:10301) is a protein-coding gene on chromosome 1p36.11, encoding Large ribosomal subunit protein uL5 (P62913). Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. It is a common-essential gene (DepMap: required in 100.0% 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 L5P family of ribosomal proteins. It is located in the cytoplasm. The protein probably associates with the 5S rRNA. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6135 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Diamond-Blackfan anemia 7 (Definitive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 222 total — 37 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 80
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_000975

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10301
Approved symbol	RPL11
Name	ribosomal protein L11
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	L11, uL5
Ensembl gene	ENSG00000142676
Ensembl biotype	protein_coding
OMIM	604175
Entrez	6135

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000374550, ENST00000443624, ENST00000458455, ENST00000467075, ENST00000482370, ENST00000643754, ENST00000895876, ENST00000933788, ENST00000933789, ENST00000933790, ENST00000933791, ENST00000933792, ENST00000933793, ENST00000933794, ENST00000933795, ENST00000933796, ENST00000933797, ENST00000933798, ENST00000933799, ENST00000933800, ENST00000933801, ENST00000970068, ENST00000970069, ENST00000970070

RefSeq mRNA: 2 — MANE Select: NM_000975 NM_000975, NM_001199802

CCDS: CCDS238, CCDS85940

Canonical transcript exons

ENST00000643754 — 6 exons

Exon	Start	End
ENSE00001463805	23691806	23691829
ENSE00003529048	23693807	23693913
ENSE00003542504	23694660	23694791
ENSE00003586241	23695798	23695908
ENSE00003655446	23692609	23692759
ENSE00003827991	23696344	23696835

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 405.3855 / max 6070.5508, expressed in 1826 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1353	395.9239	1826
1352	4.5549	1544
1354	2.5650	1255
1355	2.3418	1178

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.93	gold quality
cortical plate	UBERON:0005343	99.92	gold quality
monocyte	CL:0000576	99.90	gold quality
leukocyte	CL:0000738	99.90	gold quality
mononuclear cell	CL:0000842	99.90	gold quality
ventricular zone	UBERON:0003053	99.90	gold quality
granulocyte	CL:0000094	99.89	gold quality
skin of hip	UBERON:0001554	99.88	gold quality
right ovary	UBERON:0002118	99.88	gold quality
left ovary	UBERON:0002119	99.88	gold quality
lymph node	UBERON:0000029	99.87	gold quality
body of stomach	UBERON:0001161	99.87	gold quality
right lung	UBERON:0002167	99.87	gold quality
endocervix	UBERON:0000458	99.86	gold quality
embryo	UBERON:0000922	99.86	gold quality
rectum	UBERON:0001052	99.86	gold quality
right uterine tube	UBERON:0001302	99.86	gold quality
calcaneal tendon	UBERON:0003701	99.86	gold quality
right lobe of thyroid gland	UBERON:0001119	99.85	gold quality
left lobe of thyroid gland	UBERON:0001120	99.85	gold quality
body of pancreas	UBERON:0001150	99.85	gold quality
skin of abdomen	UBERON:0001416	99.85	gold quality
skin of leg	UBERON:0001511	99.85	gold quality
peritoneum	UBERON:0002358	99.85	gold quality
upper leg skin	UBERON:0004262	99.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.85	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.85	gold quality
body of uterus	UBERON:0009853	99.85	gold quality
omental fat pad	UBERON:0010414	99.85	gold quality
islet of Langerhans	UBERON:0000006	99.84	gold quality

Single-cell (SCXA)

Detected in 33 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	7071.55
E-CURD-88	yes	71.40
E-MTAB-9221	yes	54.99
E-MTAB-6678	yes	39.97
E-MTAB-9067	yes	29.59
E-MTAB-9543	yes	22.84
E-MTAB-10042	yes	17.03
E-CURD-112	yes	10.12
E-HCAD-35	yes	9.34
E-MTAB-9801	yes	6.38
E-GEOD-137537	yes	5.72
E-CURD-120	no	12332.61
E-CURD-55	no	10389.42
E-MTAB-6653	no	8707.08
E-MTAB-10432	no	7739.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, SPI1, TP53

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 39)

• L11 functions as a negative regulator of HDM2 and there might exist in vivo an L11-HDM2-p53 pathway for monitoring ribosomal integrity (PMID:14612427)
• L11 is not regulated by transcription or protein stability and its level remains relatively constant during serum starvation, which induces translocation of L11 from the nucleolus to the nucleoplasm, where it participates in a complex with HDM2 (PMID:15152193)
• the MDM2-L5-L11-L23 complex functions to inhibit MDM2-mediated p53 ubiquitination and thus activates p53 (PMID:15308643)
• differentially regulates the levels of ubiquitinated p53 and MDM2 and inhibits the turnover and activity of MDM2 through a post-ubiquitination mechanism (PMID:16803902)
• Cancer-associated missense mutations targeting MDM2’s central zinc finger disrupt the interaction of MDM2 with L5 and L11. (PMID:17116689)
• These results identify L11 as a feedback inhibitor of c-Myc and suggest a novel role for L11 in regulating c-Myc-enhanced ribosomal biogenesis. (PMID:17599065)
• Transcription factor YY1 participates in activation transcription of the human ribosomal protein L11 gene (PMID:18389627)
• L11 cooperates with L5, resulting in a robust inhibition of the E3 activity of MDM2, and a stabilization and activation of p53 approaching that achieved by p14(ARF). (PMID:18560357)
• RPL11 mutations are associated with abnormal thumbs in Diamond-Blackfan anemia patients. (PMID:19061985)
• Mutations in RPL11 were identified in two patients from 2 out of 28 families (7.1%). (PMID:19191325)
• The cell selectively upregulates the translation of mRNAs with a polypyrimidine tract at their 5’-transcriptional start site (5’-TOP mRNAs), including that encoding rpL11, on impairment of 40S ribosome biogenesis. (PMID:19287375)
• identify NEDD8 as a crucial regulator of L11 RP signalling to p53. A decrease in L11 NEDDylation during nucleolar stress causes relocalization of L11 from the nucleolus to the nucleoplasm. (PMID:19713960)
• The study reports a high frequency of RPL5 (9.3%) and RPL11 (9.3%) mutations in a Diamond-Blackfan anemia cohort. (PMID:19773262)
• cells survey the maturation of the small and large ribosomal subunits by separate molecular routes, which may merge in an L11-dependent signaling pathway for p53 stabilization. (PMID:20056613)
• L11 suppresses c-Myc-dependent and RNA polymerase III-catalyzed transcription of 5 S rRNA and tRNA genes in response to ribosomal stress, ensuring a tight coordination between c-Myc activity and ribosomal biogenesis. (PMID:20194507)
• Knockdown of L29 or L30 enhanced the interaction of MDM2 with L11 and L5 and markedly inhibited MDM2-mediated p53 ubiquitination, suggesting that direct perturbation of 60 S ribosomal biogenesis activates p53 via L11- and L5-mediated MDM2 suppression. (PMID:20554519)
• Data report that depletion of L37 leads to cell cycle arrest in a MDM2/L11- and p53-dependent manner. (PMID:20935493)
• Results identify a novel regulatory paradigm wherein L11 plays a critical role in controlling c-myc mRNA turnover via recruiting miR-24/miRISC in response to ribosomal stress. (PMID:21807902)
• Hydrophilic residues are crucial for ribosomal protein L11 (RPL11) interaction with zinc finger domain of MDM2 and p53 protein activation (PMID:21903592)
• The studies provide insights on how nucleolar stress through L11 and NEDD8 can activate the transcriptional activity of p53. (PMID:22081073)
• ARF activates p53, at least partly by induction of ribosomal stress, which results in L11 suppression of MDM2 (PMID:22467867)
• RPL11 mutations led to a dramatic decrease in progenitor cell proliferation and a delayed erythroid differentiation with a marked increase in apoptosis and G0/1 cell cycle arrest with activation of p53. (PMID:22833095)
• disrupted nucleoli may provide a platform for L5- and L11-dependent p53 activation, implying a role for the nucleolus in p53 activation by ribosomal biogenesis stress (PMID:23169665)
• Findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. (PMID:24045667)
• Unlike other tumor suppressors, RPL5 and RPL11 play essential roles in normal cell proliferation. (PMID:24061479)
• Findings uncover a mechanism by which RPL5 and RPL11 can co-operatively suppress c-Myc expression, allowing a tightly controlled ribosome biogenesis in cells. (PMID:24141778)
• levels of branched-chain aminotransferase-1 (BCAT1) transcripts are significantly decreased on the polysomes of both RPS19 and RPL11 cells and that translation of BCAT1 protein is especially impaired in cells with small RP gene mutations (PMID:24463277)
• Ribosomal proteins L11 and L5 activate TAp73 by overcoming MDM2 inhibition. (PMID:25301064)
• Data indicate that ribosomal protein (L11) promotes the recruitment of microRNA-130a (miR-130a) to oncoprotein c-Myc in response to UV irradiation treatment. (PMID:25544755)
• Data indicate that ribosomal protein L11 (RPL11)-expressing cells proliferated more rapidly than the ribosomal protein L11 (RPL11)-expressing cells. (PMID:25829192)
• Data suggest 5S ribosomal RNA is a direct target of miR-150 and miR-383 in esophageal squamous cell carcinoma (ESCC); overexpression of miR-150 and miR-383 inhibits ESCC cell proliferation in vitro and in vivo and intensifies RPL11/c-Myc interaction. (PMID:26606907)
• Simulation of HEY1 Ser-68 phosphorylation prevents its interaction with p53, RPL11 and MDM2 and abolishes HEY1 migration to nucleolar caps upon ribosomal stress. Our findings uncover a novel mechanism for cross-talk between Notch signalling and nucleolar stress (PMID:27129302)
• A novel pathogenic mutation in RPL11 identified in a patient diagnosed with diamond Blackfan anemia as a young adult. (PMID:27667165)
• PICT-1 is a major nucleolar sensor of the DNA damage repair response and an important upstream regulator of p53 via the RPL11-MDM2-p53 pathway. (PMID:27829214)
• RPL splicing variant is associated with Diamond-Blackfan anemia. (PMID:28742285)
• patients with RPL11 mutations were less likely to need chronic treatment. Birth defects, including cardiac, skeletal, hand, cleft lip or palate and genitourinary malformations, also varied among the various genetic groups (PMID:29044489)
• Loss of coordinated expression between ribosomal and mitochondrial genes revealed by comprehensive characterization of a large family with a rare Mendelian disorder. (PMID:33862179)
• Deficiency of the Ribosomal Protein uL5 Leads to Significant Rearrangements of the Transcriptional and Translational Landscapes in Mammalian Cells. (PMID:34948282)
• RPL11 promotes non-small cell lung cancer cell proliferation by regulating endoplasmic reticulum stress and cell autophagy. (PMID:36869281)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl11	ENSDARG00000043509
mus_musculus	Rpl11	ENSMUSG00000059291
rattus_norvegicus	Rpl11	ENSRNOG00000026260
drosophila_melanogaster	RpL11	FBGN0013325
caenorhabditis_elegans		WBGENE00004422
caenorhabditis_elegans		WBGENE00004423

Protein

Protein identifiers

Large ribosomal subunit protein uL5 — P62913 (reviewed: P62913)

Alternative names: 60S ribosomal protein L11, CLL-associated antigen KW-12

All UniProt accessions (4): P62913, A0A2R8Y447, Q5VVC8, Q5VVD0

UniProt curated annotations — full annotation on UniProt →

Function. Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs. It also couples ribosome biogenesis to p53/TP53 activation. As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53. Promotes nucleolar location of PML.

Subunit / interactions. Component of the large ribosomal subunit (LSU). Part of the 5S RNP complex, which is a LSU subcomplex composed of the 5S RNA, RPL5 and RPL11. Component of a hexameric 5S RNP precursor complex, composed of 5S RNA, RRS1, RPF2/BXDC1, RPL5, RPL11 and HEATR3; this complex acts as a precursor for ribosome assembly. Interacts with PML. Interacts with MDM2 (via its RanBP2-type zinc finger domain); negatively regulates MDM2-mediated TP53 ubiquitination and degradation. Interacts with NOP53; retains RPL11 into the nucleolus.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Disease relevance. Diamond-Blackfan anemia 7 (DBA7) [MIM:612562] An autosomal dominant form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the universal ribosomal protein uL5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P62913-1	1	yes
P62913-2	2

RefSeq proteins (2): NP_000966, NP_001186731 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002132	Ribosomal_uL5	Family
IPR020929	Ribosomal_uL5_CS	Conserved_site
IPR022803	Ribosomal_uL5_dom_sf	Homologous_superfamily
IPR031309	Ribosomal_uL5_C	Domain
IPR031310	Ribosomal_uL5_N	Domain
IPR057266	Ribosomal_uL5_euk_arc	Family

Pfam: PF00281, PF00673

UniProt features (33 total): strand 8, helix 6, modified residue 5, sequence conflict 4, cross-link 3, sequence variant 2, turn 2, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

185 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
4XXB	X-RAY DIFFRACTION	2.4
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
9QLO	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48
9P8B	ELECTRON MICROSCOPY	2.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62913-F1	91.74	0.92

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 (8): 2, 44, 47, 52, 85, 38, 52, 154

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: 472 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, MODULE_151, GCM_NPM1, MORF_UBE2I, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, GOBP_RIBOSOME_ASSEMBLY, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (16): ribosomal large subunit assembly (GO:0000027), cytoplasmic translation (GO:0002181), rRNA processing (GO:0006364), translation (GO:0006412), protein targeting (GO:0006605), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), protein localization to nucleus (GO:0034504), ribosomal large subunit biogenesis (GO:0042273), regulation of signal transduction by p53 class mediator (GO:1901796), positive regulation of signal transduction by p53 class mediator (GO:1901798), negative regulation of ubiquitin-dependent protein catabolic process (GO:2000059), positive regulation of gene expression (GO:0010628), positive regulation of protein binding (GO:0032092), protein stabilization (GO:0050821), negative regulation of ubiquitin protein ligase activity (GO:1904667), negative regulation of protein neddylation (GO:2000435)

GO Molecular Function (7): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), 5S rRNA binding (GO:0008097), ubiquitin protein ligase binding (GO:0031625), ubiquitin ligase inhibitor activity (GO:1990948), protein binding (GO:0005515), rRNA binding (GO:0019843)

GO Cellular Component (12): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062), nucleus (GO:0005634), 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	4
ribosome biogenesis	2
signal transduction by p53 class mediator	2
ribosome	2
nuclear lumen	2
intracellular membraneless organelle	2
protein-RNA complex assembly	1
ribosome assembly	1
ribosomal large subunit biogenesis	1
translation	1
RNA processing	1
rRNA metabolic process	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
establishment of protein localization	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
protein localization to organelle	1
ribonucleoprotein complex biogenesis	1
regulation of intracellular signal transduction	1
regulation of signal transduction by p53 class mediator	1
positive regulation of intracellular signal transduction	1
ubiquitin-dependent protein catabolic process	1
negative regulation of protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
protein binding	1
regulation of protein binding	1
positive regulation of binding	1
regulation of protein stability	1
negative regulation of ubiquitin-protein transferase activity	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

305 interactions, top by confidence:

A	B	Type	Score
RPL11	MDM2	psi-mi:“MI:0915”(physical association)	0.920
MDM2	RPL11	psi-mi:“MI:0915”(physical association)	0.920
NCAPH2	SMC2	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RPL10A	RPL11	psi-mi:“MI:0915”(physical association)	0.670
MDM2	RPL5	psi-mi:“MI:0914”(association)	0.670
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPL11	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
CAMK2B	RPL11	psi-mi:“MI:0915”(physical association)	0.560
KRT40	RPL11	psi-mi:“MI:0915”(physical association)	0.560
RPL11	CAMK2B	psi-mi:“MI:0915”(physical association)	0.560
RPL11	KRT40	psi-mi:“MI:0915”(physical association)	0.560
NOM1	RPLP0	psi-mi:“MI:0914”(association)	0.530
RBM8A	RPS16	psi-mi:“MI:0914”(association)	0.530
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
RPL11	HSP90AB1	psi-mi:“MI:0914”(association)	0.500
HSP90AB1	RPL11	psi-mi:“MI:0915”(physical association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (1127): RPL11 (Affinity Capture-MS), PML (Affinity Capture-Western), RPL11 (Co-fractionation), RPL11 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), RPL11 (Affinity Capture-MS), RPL11 (Affinity Capture-MS), RPL11 (Affinity Capture-MS), RPL11 (Affinity Capture-MS), RPL11 (Affinity Capture-Western), MDM2 (Affinity Capture-Western), RPL11 (Affinity Capture-MS), BRIX1 (Co-fractionation), FAU (Co-fractionation)

ESM2 similar proteins: A4FUD3, A4FV84, F4JGR5, G1TUB8, O08810, O80526, O95045, P11497, P21343, P42932, P50990, P62913, P62914, Q13085, Q15029, Q28559, Q29205, Q2QNG7, Q2QZ86, Q2YDN6, Q3T087, Q3ZCI9, Q4R5J0, Q5F3X4, Q5M939, Q5R6E0, Q5R8Q7, Q5R8T5, Q5RAP1, Q5RC11, Q5RCW2, Q5SWU9, Q5XGS8, Q5XK67, Q5ZID6, Q5ZJ08, Q6EE31, Q6QMZ8, Q80YV4, Q80Z29

Diamond homologs: A0A1D8PHW1, A0RVY6, A2SPL5, A2YDY2, A3CT10, A4FWA8, A5UL75, A5VQZ4, A6U871, A6UQ57, A6UWV1, A6VGZ8, A7HWS3, A7I5Q2, A7IPQ8, A8IAQ3, A8MB19, A8WQ43, A8XJ93, A9A5I2, A9A9Q1, A9M5N8, B0R669, B2S667, B3PWT3, B5ZYU7, B9JDU0, B9JVP9, B9LSR4, C0RJI9, C3MAZ2, G0SHQ2, G1TUB8, O26124, O28367, O59431, P0C0W9, P0CT77, P0CT78, P14029

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RPL11	up-regulates	TP73	binding
RPL11	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 205 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TRAF6 mediated NF-kB activation	5	15.4×	6e-04
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	19	15.1×	7e-15
Peptide chain elongation	17	14.6×	3e-13
Eukaryotic Translation Termination	17	13.8×	6e-13
Viral mRNA Translation	16	13.7×	2e-12
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	16	13.6×	2e-12
SRP-dependent cotranslational protein targeting to membrane	20	13.5×	7e-15
Nuclear events stimulated by ALK signaling in cancer	6	13.2×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	18	18.2×	6e-15
positive regulation of transcription by RNA polymerase I	5	17.7×	1e-03
mitophagy	10	17.4×	1e-07
ribosomal large subunit biogenesis	7	17.0×	3e-05
stress granule assembly	5	16.4×	1e-03
intrinsic apoptotic signaling pathway	6	11.8×	1e-03
translation	20	11.2×	8e-13
ribosomal small subunit biogenesis	9	11.2×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	10
Uncertain significance	62
Likely benign	66
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100640	NM_000975.5(RPL11):c.476_477del (p.Lys159fs)	Pathogenic
100641	NM_000975.5(RPL11):c.204del (p.Ile68fs)	Pathogenic
1069986	NM_000975.5(RPL11):c.121G>T (p.Glu41Ter)	Pathogenic
1074653	NM_000975.5(RPL11):c.107del (p.Ala36fs)	Pathogenic
1363160	NM_000975.5(RPL11):c.151dup (p.Ser51fs)	Pathogenic
1705531	NM_000975.5(RPL11):c.124C>T (p.Gln42Ter)	Pathogenic
1708160	NM_000975.5(RPL11):c.94_97del (p.Asp31_Arg32insTer)	Pathogenic
1729829	NM_000975.5(RPL11):c.328C>T (p.Gln110Ter)	Pathogenic
1731025	NM_000975.5(RPL11):c.33del (p.Met12fs)	Pathogenic
1770758	NM_000975.5(RPL11):c.102dup (p.Arg35fs)	Pathogenic
1775715	NM_000975.5(RPL11):c.158-1G>C	Pathogenic
1775730	NM_000975.5(RPL11):c.158-2A>C	Pathogenic
1798396	NM_000975.5(RPL11):c.298_299del (p.Ser100fs)	Pathogenic
1808450	GRCh37/hg19 1p36.11(chr1:23980892-24024498)x1	Pathogenic
2010907	NM_000975.5(RPL11):c.96_109del (p.Arg32fs)	Pathogenic
2423444	NC_000001.10:g.(?24021140)(24022863_?)del	Pathogenic
2431941	NM_000975.5(RPL11):c.95_96del (p.Arg32fs)	Pathogenic
2733860	NM_000975.5(RPL11):c.100dup (p.Thr34fs)	Pathogenic
280297	NM_000975.5(RPL11):c.116dup (p.Leu40fs)	Pathogenic
2828833	NM_000975.5(RPL11):c.301_302del (p.Asp101fs)	Pathogenic
2839617	NM_000975.5(RPL11):c.311del (p.Asn104fs)	Pathogenic
3256521	NM_000975.5(RPL11):c.165C>A (p.Tyr55Ter)	Pathogenic
3655059	NM_000975.5(RPL11):c.501_502delinsCT (p.Gln167_Gln168delinsHisTer)	Pathogenic
451147	NM_000975.5(RPL11):c.143_144del (p.Pro48fs)	Pathogenic
4723240	NM_000975.5(RPL11):c.136C>T (p.Gln46Ter)	Pathogenic
4739066	NM_000975.5(RPL11):c.290dup (p.Asn97fs)	Pathogenic
522687	NM_000975.5(RPL11):c.43_49del (p.Leu15fs)	Pathogenic
532180	NM_000975.5(RPL11):c.111del (p.Lys38fs)	Pathogenic
5751	NM_000975.5(RPL11):c.223C>T (p.Arg75Ter)	Pathogenic
5752	NM_000975.5(RPL11):c.60_61del (p.Cys21fs)	Pathogenic

SpliceAI

916 predictions. Top by Δscore:

Variant	Effect	Δscore
1:23692601:T:TA	acceptor_gain	1.0000
1:23692603:TTGCA:T	acceptor_loss	1.0000
1:23692604:TGCA:T	acceptor_loss	1.0000
1:23692606:CAGC:C	acceptor_loss	1.0000
1:23692606:CAGCA:C	acceptor_gain	1.0000
1:23692607:A:AG	acceptor_gain	1.0000
1:23692607:A:C	acceptor_loss	1.0000
1:23692607:AGCAG:A	acceptor_gain	1.0000
1:23692608:G:C	acceptor_loss	1.0000
1:23692608:G:GA	acceptor_gain	1.0000
1:23692608:GC:G	acceptor_gain	1.0000
1:23692608:GCA:G	acceptor_gain	1.0000
1:23692608:GCAGG:G	acceptor_gain	1.0000
1:23692611:GGATC:G	acceptor_gain	1.0000
1:23692755:CAAAG:C	donor_gain	1.0000
1:23692756:AAAG:A	donor_gain	1.0000
1:23692757:AAG:A	donor_gain	1.0000
1:23692758:AG:A	donor_gain	1.0000
1:23692759:GG:G	donor_gain	1.0000
1:23692760:G:GG	donor_gain	1.0000
1:23693802:T:A	acceptor_gain	1.0000
1:23693805:A:AG	acceptor_gain	1.0000
1:23693806:G:GT	acceptor_gain	1.0000
1:23693806:GC:G	acceptor_gain	1.0000
1:23693806:GCT:G	acceptor_gain	1.0000
1:23693806:GCTA:G	acceptor_gain	1.0000
1:23693907:TCTAA:T	donor_gain	1.0000
1:23693910:AAAG:A	donor_loss	1.0000
1:23693911:AAGG:A	donor_loss	1.0000
1:23693914:G:C	donor_loss	1.0000

AlphaMissense

1168 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:23693827:T:C	F60L	1.000
1:23693829:T:A	F60L	1.000
1:23693829:T:G	F60L	1.000
1:23693840:G:C	R64T	1.000
1:23693841:A:C	R64S	1.000
1:23693841:A:T	R64S	1.000
1:23694676:T:C	L94S	1.000
1:23694714:T:C	F107L	1.000
1:23694716:T:A	F107L	1.000
1:23694716:T:G	F107L	1.000
1:23694718:G:A	G108E	1.000
1:23694733:T:A	I113N	1.000
1:23694750:T:C	Y119H	1.000
1:23694766:G:A	G124D	1.000
1:23692667:T:A	L22H	0.999
1:23692681:G:A	G27R	0.999
1:23692681:G:C	G27R	0.999
1:23692681:G:T	G27W	0.999
1:23692682:G:A	G27E	0.999
1:23692682:G:T	G27V	0.999
1:23692690:G:A	G30R	0.999
1:23692690:G:C	G30R	0.999
1:23692691:G:A	G30E	0.999
1:23692693:G:C	D31H	0.999
1:23692709:C:A	A36E	0.999
1:23692711:G:C	A37P	0.999
1:23693807:C:A	A53D	0.999
1:23693816:C:T	T56I	0.999
1:23693822:G:C	R58T	0.999
1:23693822:G:T	R58I	0.999

dbSNP variants (sampled 300 via entrez): RS1001063696 (1:23695837 C>T), RS1001115443 (1:23696084 C>T), RS1001345476 (1:23689857 C>T), RS1001436562 (1:23695215 T>C,G), RS1001727065 (1:23692707 A>C,G), RS1001779456 (1:23692991 A>G), RS1001982522 (1:23691162 T>A), RS1002622139 (1:23696533 A>G), RS1003041675 (1:23696807 G>A), RS1003402764 (1:23691631 G>A,C,T), RS1003634392 (1:23694235 G>A,T), RS1004308258 (1:23695341 C>A,T), RS1004345712 (1:23691884 G>A,T), RS1004702739 (1:23694950 A>G), RS1005123599 (1:23690310 T>C)

Disease associations

OMIM: gene MIM:604175 | disease phenotypes: MIM:612562, MIM:105650

GenCC curated gene-disease

Disease	Classification	Inheritance
Diamond-Blackfan anemia 7	Definitive	Autosomal dominant
Diamond-Blackfan anemia	Supportive	Autosomal dominant

Mondo (3): Diamond-Blackfan anemia 7 (MONDO:0012938), Diamond-Blackfan anemia (MONDO:0015253), anemia (MONDO:0002280)

Orphanet (1): Diamond-Blackfan anemia (Orphanet:124)

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000085	Horseshoe kidney
HP:0000104	Renal agenesis
HP:0000119	Abnormality of the genitourinary system
HP:0000175	Cleft palate
HP:0000185	Cleft soft palate
HP:0000218	High palate
HP:0000234	Abnormality of the head
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000413	Atresia of the external auditory canal
HP:0000431	Wide nasal bridge
HP:0000453	Choanal atresia
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000519	Developmental cataract
HP:0000912	Sprengel anomaly
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000980	Pallor

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000740	Anemia	C15.378.050
D029503	Anemia, Diamond-Blackfan	C15.378.050.085.080.090; C15.378.050.750.500; C15.378.190.223.500.500.090; C16.320.077.090
C567254	Diamond-Blackfan Anemia 7 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067549 (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
7.40	Kd	39.54	nM	CHEMBL3752910
7.40	ED50	39.54	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
5.79	Kd	1632	nM	CHEMBL5653589
5.79	ED50	1632	nM	CHEMBL5653589
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

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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149241: Binding affinity to human RPL11 incubated for 45 mins by Kinobead based pull down assay	kd	0.0395	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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149241: Binding affinity to human RPL11 incubated for 45 mins by Kinobead based pull down assay	kd	1.6324	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	decreases expression, increases methylation	3
sodium arsenite	decreases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases expression, affects expression	2
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
deoxynivalenol	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
zinc chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
azoxystrobin	increases expression	1
CGP 52608	increases reaction, affects binding	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
deguelin	increases expression	1
fenpyroximate	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
olomoucine II	decreases activity, increases reaction, affects binding	1
pyrimidifen	increases expression	1
bisphenol B	increases expression	1
pyrachlostrobin	increases expression	1
hexabrominated diphenyl ether 153	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)

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

Trial	Phase	Status	Title
NCT00673608	PHASE4	COMPLETED	Magnetic Resonance Imaging (MRI) Assessments of the Heart and Liver Iron Load in Patients With Transfusion Induced Iron Overload
NCT00003398	PHASE4	COMPLETED	Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00046969	PHASE4	COMPLETED	Epoetin Beta in Treating Anemia in Patients With Cervical Cancer
NCT00111995	PHASE4	COMPLETED	Evaluating Aranesp® for the Treatment of Anemia in African-American Subjects With Chronic Renal Failure (CRF) Receiving Hemodialysis
NCT00117039	PHASE4	COMPLETED	A Study to Evaluate the Effectiveness of Aranesp® for Cancer Patients With Anemia
NCT00117065	PHASE4	COMPLETED	Study of Transplant Related Anemia Treated With Aranesp® (STRATA)
NCT00117117	PHASE4	COMPLETED	A Study to Assess Symptom Burden in Subjects With Nonmyeloid Malignancies Receiving Chemotherapy and Aranesp®
NCT00126334	PHASE4	COMPLETED	Conservative Versus Liberal Red Cell Transfusion in Myocardial Infarction Trial: The CRIT Pilot
NCT00153868	PHASE4	COMPLETED	A Web-based Study of Quality of Life Benefits Associated Aranesp in Anemic Patients With Cancer
NCT00168948	PHASE4	UNKNOWN	Intermittent Antimalaria Treatment With SP in African Children
NCT00173706	PHASE4	UNKNOWN	Evaluation of the Effects of L-Carnitine Injection in Patients Undergoing Hemodialysis
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00204334	PHASE4	COMPLETED	Effects of Anemia Correction on Vascular and Monocyte Function in Renal Transplant Recipients
NCT00206739	PHASE4	COMPLETED	Intermittent Treatment With Sulfadoxine-pyrimethamine for Malaria Control in Infants
NCT00211120	PHASE4	TERMINATED	Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR)
NCT00216541	PHASE4	COMPLETED	A Study of the Safety and Effectiveness of Epoetin Alfa on Hemoglobin Levels and Blood Transfusions in Cancer Patients Receiving Chemotherapy
NCT00223938	PHASE4	TERMINATED	Study of the Efficacy and Safety of Ferrlecit in the Maintenance Dosing in Hemodialysis Patients.
NCT00223964	PHASE4	COMPLETED	Study of the Efficacy of Two Doses of Ferrlecit in the Treatment of Iron Deficiency in Pediatric Hemodialysis Patients
NCT00224003	PHASE4	COMPLETED	Study of the Safety and Efficacy of Ferrlecit® Maintenance Dosing in Pediatric Hemodialysis Patients
NCT00224068	PHASE4	COMPLETED	Effect of Iron Therapy as an Adjunct to Epoetin Alfa in the Anemia of Cancer Chemotherapy
NCT00239642	PHASE4	COMPLETED	Safety and Efficacy of Iron Sucrose in Children
NCT00247507	PHASE4	UNKNOWN	The Effects of Acetylcysteine on Alleviating Damage of Oxidative Stress in Hemodialysis Patients
NCT00248716	PHASE4	UNKNOWN	Treatment of Anemia in the 2nd Year of Life. Comparison of the Efficacy of Two Different Iron Preparations.
NCT00283465	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Treatment With Epoetin Alfa on Hemoglobin Levels, Red Blood Cell Transfusions, and Quality of Life in Patients With Cancer Receiving Platinum-containing Chemotherapy
NCT00312871	PHASE4	TERMINATED	Effects of Early Correction of Anemia in Patients With Chronic Renal Insufficiency
NCT00315484	PHASE4	COMPLETED	Hematologic Response of Epoetin Alfa (PROCRIT) Versus Darbepoetin Alfa (ARANESP) in Chemotherapy Induced Anemia
NCT00317902	PHASE4	COMPLETED	An Open-Label Study to Evaluate the Effect of Every Other Week PROCRIT� (Epoetin Alfa) Dosing (40,000-60,000 Units) On Maintaining Quality of Life and Target Hemoglobin Levels in Anemic HIV-Infected Patients (CHAMPS II)
NCT00335023	PHASE4	COMPLETED	Well Being of Obstetric Patients on Minimal Blood Transfusions
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00377481	PHASE4	COMPLETED	COMFORT Study: A Crossover Study of NeoRecormon (Epoetin Beta) and Darbepoetin Alfa in Patients With Renal Anemia.
NCT00396435	PHASE4	COMPLETED	Correction of Anaemia and Progression of Renal Failure on Transplanted Patients
NCT00401869	PHASE4	COMPLETED	The Effect of PROCRIT (Epoetin Alfa) on Postoperative Vigor and Handgrip Strength (VIGOR Study)
NCT00413101	PHASE4	COMPLETED	A Study of NeoRecormon (Epoetin Beta) in Patients With End Stage Renal Disease.
NCT00431496	PHASE4	COMPLETED	A Study of Cinacalcet to Improve Achievement of National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) Targets in Patients With End Stage Renal Disease (ESRD)
NCT00437723	PHASE4	COMPLETED	A Study of NeoRecormon in Patients With Chronic Kidney Disease.
NCT00440063	PHASE4	TERMINATED	A Study of NeoRecormon (Epoetin Beta) in Patients With Renal Anemia.
NCT00470158	PHASE4	COMPLETED	Delivery of Iron and Zinc Supplements: Evaluation of Interaction Effect on Biochemical and Clinical Outcomes
NCT00479102	PHASE4	UNKNOWN	Prevention of Iron Deficiency in 2nd Year of Life
NCT00495365	PHASE4	TERMINATED	A Dose Conversion Study of Epoetin Alfa in Subjects With the Anemia of Chronic Kidney Disease.