RPL5

Summary

RPL5 (ribosomal protein L5, HGNC:10360) is a protein-coding gene on chromosome 1p22.1, encoding Large ribosomal subunit protein uL18 (P46777). 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 four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L18P family of ribosomal proteins and component of the 60S subunit. The encoded protein binds 5S rRNA to form a stable complex called the 5S ribonucleoprotein particle (RNP), which is necessary for the transport of nonribosome-associated cytoplasmic 5S rRNA to the nucleolus for assembly into ribosomes. The encoded protein may also function to inhibit tumorigenesis through the activation of downstream tumor suppressors and the downregulation of oncoprotein expression. Mutations in this gene have been identified in patients with Diamond-Blackfan Anemia (DBA). This gene is co-transcribed with the small nucleolar RNA gene U21, which is located in its fifth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome.

Source: NCBI Gene 6125 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Diamond-Blackfan anemia 6 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 82 total — 16 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 72
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_000969

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10360
Approved symbol	RPL5
Name	ribosomal protein L5
Location	1p22.1
Locus type	gene with protein product
Status	Approved
Aliases	L5, PPP1R135, uL18
Ensembl gene	ENSG00000122406
Ensembl biotype	protein_coding
OMIM	603634
Entrez	6125

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 16 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000315741, ENST00000370321, ENST00000461952, ENST00000470843, ENST00000497519, ENST00000643510, ENST00000644549, ENST00000645119, ENST00000645300, ENST00000645908, ENST00000646852, ENST00000880514, ENST00000880515, ENST00000880516, ENST00000880517, ENST00000880518, ENST00000880519, ENST00000933849, ENST00000933850, ENST00000933851, ENST00000933852, ENST00000933853, ENST00000933854

RefSeq mRNA: 1 — MANE Select: NM_000969 NM_000969

CCDS: CCDS741

Canonical transcript exons

ENST00000370321 — 8 exons

Exon	Start	End
ENSE00001897153	92841766	92841924
ENSE00002260159	92836190	92836392
ENSE00003387580	92837456	92837633
ENSE00003466739	92833545	92833660
ENSE00003467828	92834779	92834913
ENSE00003468375	92840551	92840639
ENSE00003509347	92833389	92833458
ENSE00003819363	92832040	92832117

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1188.1593 / max 32663.5389, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4044	1126.9160	1827
4045	40.3836	1797
4043	17.6842	1762
4047	2.4675	1098
4046	0.7079	388

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	99.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.92	gold quality
parietal pleura	UBERON:0002400	99.92	gold quality
epithelium of nasopharynx	UBERON:0001951	99.90	gold quality
cortical plate	UBERON:0005343	99.90	gold quality
tibia	UBERON:0000979	99.88	gold quality
ovary	UBERON:0000992	99.88	gold quality
left ovary	UBERON:0002119	99.88	gold quality
pleura	UBERON:0000977	99.86	gold quality
right ovary	UBERON:0002118	99.86	gold quality
palpebral conjunctiva	UBERON:0001812	99.85	gold quality
ventricular zone	UBERON:0003053	99.84	gold quality
embryo	UBERON:0000922	99.83	gold quality
ganglionic eminence	UBERON:0004023	99.83	gold quality
lower lobe of lung	UBERON:0008949	99.83	gold quality
body of uterus	UBERON:0009853	99.83	gold quality
islet of Langerhans	UBERON:0000006	99.82	gold quality
endocervix	UBERON:0000458	99.82	gold quality
mammary duct	UBERON:0001765	99.82	gold quality
adenohypophysis	UBERON:0002196	99.82	gold quality
calcaneal tendon	UBERON:0003701	99.82	gold quality
pituitary gland	UBERON:0000007	99.81	gold quality
left lobe of thyroid gland	UBERON:0001120	99.81	gold quality
endometrium	UBERON:0001295	99.81	gold quality
colonic epithelium	UBERON:0000397	99.80	gold quality
eye	UBERON:0000970	99.80	gold quality
seminal vesicle	UBERON:0000998	99.80	gold quality
mucosa of stomach	UBERON:0001199	99.80	gold quality
mammary gland	UBERON:0001911	99.80	gold quality
thyroid gland	UBERON:0002046	99.80	gold quality

Single-cell (SCXA)

Detected in 41 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	4481.96
E-GEOD-125970	yes	4316.75
E-MTAB-9543	yes	3885.18
E-CURD-122	yes	98.84
E-CURD-88	yes	65.00
E-CURD-46	yes	61.74
E-MTAB-9221	yes	55.24
E-HCAD-11	yes	48.90
E-MTAB-6678	yes	39.02
E-MTAB-9067	yes	29.82
E-HCAD-13	yes	28.38
E-HCAD-9	yes	23.98
E-CURD-112	yes	21.12
E-MTAB-10042	yes	15.98
E-MTAB-7316	yes	14.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 36)

• the presence of multiple NLSs in ribosomal protein L5 appears to allow for efficient nuclear transport via utilisation of multiple, mechanistically different import pathways. (PMID:11824785)
• the MDM2-L5-L11-L23 complex functions to inhibit MDM2-mediated p53 ubiquitination and thus activates p53 (PMID:15308643)
• interaction of NVL2 with L5 is ATP-dependent and likely contributes to the nucleolar translocation of NVL2 (PMID:15469983)
• Cancer-associated missense mutations targeting MDM2’s central zinc finger disrupt the interaction of MDM2 with L5 and L11. (PMID:17116689)
• 5-FU treatment triggers a ribosomal stress response so that ribosomal proteins L5, L11, and L23 are released from ribosome to activate p53 by ablating the MDM2-p53 feedback circuit (PMID:17242401)
• 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)
• Susceptibility gene for multiple sclerosis in Australians. (PMID:18650830)
• RPL5 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. (PMID:19061985)
• Mutations in RPL5 were identified in eight patients from 6 out of 28 families (21.4%). (PMID:19191325)
• The study reports a high frequency of RPL5 (9.3%) and RPL11 (9.3%) mutations in a Diamond-Blackfan anemia cohort. (PMID:19773262)
• An analysis and fine mapping of GFI-EVI5-RPL5-FAM69A locus, genotyping eight Tag-single nucleotide polymorphisms in 732 multiple sclerosis patients and 974 controls from Spain, was performed. (PMID:20087403)
• Data show that all patients with RPS19 and RPL5 mutations had physical abnormalities. (PMID:20378560)
• 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 show 1 proband with an RPL5 deletion, 1 patient with an RPL35A deletion, 3 with RPS17 deletions, and 1 with an RPS19 deletion. (PMID:22262766)
• High frequency of RPL5 gene deletion is associated with Italian Diamond-Blackfan anemia. (PMID:22689679)
• 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)
• Mutations affect the ribosomal proteins RPL5 and RPL10 in 12 of 122 (9.8%) pediatric T-cell acute lymphoblastic leukemias. (PMID:23263491)
• Oncogenic splicing factor SRSF1 stabilizes the tumor suppressor protein p53 via RPL5, inducing cell senescence. (PMID:23478443)
• 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)
• RPL5 mutation is associated with Diamond Blackfan Anemia. (PMID:25132370)
• Ribosomal proteins L11 and L5 activate TAp73 by overcoming MDM2 inhibition. (PMID:25301064)
• Low RPL5 expression is associated with cancer. (PMID:28147343)
• Whole exome sequencing in the differential diagnosis of Diamond-Blackfan anemia: Clinical and molecular study of three patients with novel RPL5 and mosaic RPS19 mutations (PMID:28376382)
• RPL5 remains an interesting candidate in multiple myelom(MM )because it is deleted in 20-40% of MM cases (PMID:28428269)
• Patients with RPS19 mutations had the fewest number of defects, while patients with RPL5 had the greatest number of birth defects. This is the first study to show differences between Diamond-Blackfan anemia (DBA) genetic groups with regards to treatment. (PMID:29044489)
• Our results also show extra-ribosomal uL18/L5 is formed during 60S assembly, not during degradation of mature cytoplasmic 60S subunits. (PMID:31986150)
• Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint. (PMID:32108164)
• The important role of MDM2, RPL5, and TP53 in mycophenolic acid-induced cleft lip and palate. (PMID:34032749)
• Identification of RPL5 gene variants and the risk of hepatic vein thrombosis in Saudi patients. (PMID:34470834)
• Genetic Variants of RPL5 and RPL9 Genes among Saudi Patients Diagnosed with Thrombosis. (PMID:34483448)
• Investigation of the molecular causes underlying physical abnormalities in Diamond-Blackfan anemia patients with RPL5 haploinsufficiency. (PMID:34587661)
• Ribosomal protein L5 (RPL5)/ E2F transcription factor 1 (E2F1) signaling suppresses breast cancer progression via regulating endoplasmic reticulum stress and autophagy. (PMID:35293275)
• Ribosomal protein L5 facilitates rDNA-bundled condensate and nucleolar assembly. (PMID:35321919)
• DDX24 promotes metastasis by regulating RPL5 in non-small cell lung cancer. (PMID:35864588)
• Ribosomal protein RPL5 regulates colon cancer cell proliferation and migration through MAPK/ERK signaling pathway. (PMID:36384455)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl5b	ENSDARG00000015862
danio_rerio	rpl5a	ENSDARG00000020197
mus_musculus	Rpl5	ENSMUSG00000058558
rattus_norvegicus	Rpl5l1	ENSRNOG00000023529
rattus_norvegicus		ENSRNOG00000073774
drosophila_melanogaster	RpL5	FBGN0064225
caenorhabditis_elegans		WBGENE00004416

Protein

Protein identifiers

Large ribosomal subunit protein uL18 — P46777 (reviewed: P46777)

Alternative names: 60S ribosomal protein L5

All UniProt accessions (6): A0A2R8Y4A2, A0A2R8Y6J3, A2RUM7, P46777, Q5T7N0, R4GNJ2

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.

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 isoform 1 of NVL in an ATP-dependent manner. Interacts with RRP1B. Interacts with IPO5, IPO7 and KPNB1; these interactions may be involved in RPL5 nuclear import for the assembly of ribosomal subunits.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Disease relevance. Diamond-Blackfan anemia 6 (DBA6) [MIM:612561] 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 uL18 family.

RefSeq proteins (1): NP_000960* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005485	Rbsml_uL18_euk_arc	Family
IPR025607	Ribosomal_uL18_C_euk	Domain
IPR057268	Ribosomal_L18	Family

Pfam: PF14204, PF17144

UniProt features (19 total): modified residue 7, sequence variant 3, sequence conflict 3, cross-link 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

184 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
9QLO	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48
9P8B	ELECTRON MICROSCOPY	2.48
7XNY	ELECTRON MICROSCOPY	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46777-F1	94.53	0.91

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 (9): 272, 220, 220, 2, 5, 48, 185, 220, 232

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: 498 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, TGCGCANK_UNKNOWN, LU_IL4_SIGNALING, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, MAZ_Q6, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_RIBOSOME_ASSEMBLY, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (12): ribosomal large subunit assembly (GO:0000027), cytoplasmic translation (GO:0002181), rRNA processing (GO:0006364), translation (GO:0006412), ribosomal large subunit biogenesis (GO:0042273), positive regulation of translation (GO:0045727), regulation of signal transduction by p53 class mediator (GO:1901796), negative regulation of ubiquitin-dependent protein catabolic process (GO:2000059), positive regulation of gene expression (GO:0010628), protein stabilization (GO:0050821), negative regulation of ubiquitin protein ligase activity (GO:1904667), negative regulation of protein neddylation (GO:2000435)

GO Molecular Function (9): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), structural constituent of ribosome (GO:0003735), 5S rRNA binding (GO:0008097), ubiquitin protein ligase binding (GO:0031625), mRNA 5’-UTR binding (GO:0048027), ubiquitin ligase inhibitor activity (GO:1990948), protein binding (GO:0005515), rRNA binding (GO:0019843)

GO Cellular Component (14): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062), ribonucleoprotein complex (GO:1990904), ribosome (GO:0005840)

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
translation	2
ribosome biogenesis	2
mRNA binding	2
ribosome	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
intracellular membraneless organelle	2
cytoplasm	2
protein-RNA complex assembly	1
ribosome assembly	1
ribosomal large subunit biogenesis	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
ribonucleoprotein complex biogenesis	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
signal transduction by p53 class mediator	1
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
regulation of protein stability	1
negative regulation of ubiquitin-protein transferase activity	1
ubiquitin protein ligase activity	1
regulation of ubiquitin protein ligase activity	1
protein neddylation	1
negative regulation of protein modification by small protein conjugation or removal	1
regulation of protein neddylation	1

Protein interactions and networks

STRING

4638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL5	RPL11	P25121	999
RPL5	MDM2	Q00987	996
RPL5	LILRB1	Q8NHL6	995
RPL5	RPS10	P46783	968
RPL5	RPS5	P46782	957
RPL5	RPS9	P46781	954
RPL5	RPL21	P46778	947
RPL5	RPS29	P30054	946
RPL5	RPS26	P02383	941
RPL5	RPS19	P39019	940
RPL5	RPL27A	P46776	918
RPL5	RPL28	P46779	913
RPL5	RPS24	P16632	909
RPL5	RPL35A	P18077	907
RPL5	LILRA6	Q6PI73	901

IntAct

324 interactions, top by confidence:

A	B	Type	Score
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DCC	NTN1	psi-mi:“MI:0914”(association)	0.700
MDM2	RPL5	psi-mi:“MI:0914”(association)	0.670
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
RPS7	RPL5	psi-mi:“MI:0914”(association)	0.640
RRP1B	RPL5	psi-mi:“MI:0915”(physical association)	0.620
Dcc	RPL5	psi-mi:“MI:0915”(physical association)	0.620
Dcc	RPL5	psi-mi:“MI:0407”(direct interaction)	0.620
RPL5	Dcc	psi-mi:“MI:0403”(colocalization)	0.620
RPL5	Dcc	psi-mi:“MI:0915”(physical association)	0.620
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
DCC	RPL5	psi-mi:“MI:0915”(physical association)	0.610
RPL5	RPL23	psi-mi:“MI:0915”(physical association)	0.560
RPL5	RPS23	psi-mi:“MI:0915”(physical association)	0.560
RPL5	CSNK2B	psi-mi:“MI:0915”(physical association)	0.550
RPL4	RPL5	psi-mi:“MI:0914”(association)	0.530
PLEKHO1	UBA6	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MAGEB10	GTPBP10	psi-mi:“MI:0914”(association)	0.530

BioGRID (1066): RPL5 (Affinity Capture-MS), PML (Affinity Capture-Western), RPL11 (Co-fractionation), RPL5 (Affinity Capture-MS), RPL5 (Affinity Capture-MS), RPL5 (Affinity Capture-MS), RPL5 (Affinity Capture-MS), RPL5 (Affinity Capture-MS), RPL5 (Affinity Capture-MS), RPL5 (Affinity Capture-MS), RPL5 (Affinity Capture-MS), RPL5 (Two-hybrid), ATP6V0D1 (Co-fractionation), DDX24 (Co-fractionation), EEF1A1 (Co-fractionation)

ESM2 similar proteins: A1KNP2, A2WXX3, A4YKV0, A5ETE1, A5U7R4, A9B6X4, B3DR89, B7GQH1, G0SEG2, O22608, O59953, O65353, O74306, O76190, P09895, P0A5Y9, P15125, P15126, P19949, P22451, P26321, P46777, P47962, P49227, P49405, P52822, P9WGP4, P9WGP5, Q0JGY1, Q1HQU2, Q231U7, Q26481, Q3SVN4, Q4KTI3, Q4N655, Q4R5M0, Q4UDE7, Q54XX3, Q56FG6, Q58DW5

Diamond homologs: A0B9V1, A1RVN4, A1RWR7, A2BMD8, A2SPM1, A2WXX3, A3CT16, A3DNC6, A3MSJ3, A4FWA2, A4WMD6, A4YCY5, A5UL69, A6UQ63, A6UWV7, A6VH04, A7I5Q8, A8AC01, A8M9I3, A9A9P5, B0R675, B1L785, B1Y8V2, B6YSN3, B8D5V1, B8GKF2, B9LSQ8, C3MQ78, C3MVJ7, C3N5U6, C3NEG2, C3NH90, C4KHH5, C5A266, C6A179, G0SEG2, O05640, O22608, O26130, O28373

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
DAPK1	unknown	RPL5	phosphorylation
RPL5	up-regulates	TP73	binding
RPL5	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 223 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
Formation of the ternary complex, and subsequently, the 43S complex	12	16.9×	2e-10
SRP-dependent cotranslational protein targeting to membrane	25	16.4×	5e-21
Eukaryotic Translation Initiation	8	16.1×	7e-07
Cap-dependent Translation Initiation	8	16.1×	7e-07
SARS-CoV-1 modulates host translation machinery	8	16.1×	7e-07
Response of EIF2AK4 (GCN2) to amino acid deficiency	22	15.9×	1e-18
Peptide chain elongation	19	15.8×	4e-16
Viral mRNA Translation	19	15.8×	4e-16

GO biological processes:

GO term	Partners	Fold	FDR
stress granule assembly	7	21.5×	6e-06
cytoplasmic translation	22	20.8×	4e-20
ribosomal large subunit biogenesis	8	18.1×	3e-06
translational initiation	8	14.6×	1e-05
rRNA processing	16	11.6×	2e-10
mitophagy	7	11.4×	4e-04
translation	21	11.0×	2e-13
intrinsic apoptotic signaling pathway	6	11.0×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — GBM, LUAD, MEL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	3
Uncertain significance	21
Likely benign	17
Benign	9

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1069070	NM_000969.5(RPL5):c.1A>C (p.Met1Leu)	Pathogenic
1073746	NC_000001.10:g.(?93297672)(93307422_?)del	Pathogenic
1074389	NM_000969.5(RPL5):c.153del (p.Met51fs)	Pathogenic
1700812	NM_000969.5(RPL5):c.1A>G (p.Met1Val)	Pathogenic
1735599	NM_000969.5(RPL5):c.385G>T (p.Glu129Ter)	Pathogenic
1736900	NM_000969.5(RPL5):c.3G>A (p.Met1Ile)	Pathogenic
1738073	NM_000969.5(RPL5):c.412C>T (p.Gln138Ter)	Pathogenic
1763241	NM_000969.5(RPL5):c.83del (p.Thr28fs)	Pathogenic
1794904	NM_000969.5(RPL5):c.26del (p.Asn9fs)	Pathogenic
2202776	NM_000969.5(RPL5):c.2T>G (p.Met1Arg)	Pathogenic
463366	NM_000969.5(RPL5):c.256dup (p.Tyr86fs)	Pathogenic
532183	NC_000001.11:g.(?92832109)(92833666_?)del	Pathogenic
6183	RPL5, 5-BP DEL/39-BP INS, NT498	Pathogenic
662012	NM_000969.5(RPL5):c.175_176del (p.Asp59fs)	Pathogenic
930202	NM_000969.5(RPL5):c.268del (p.Val90fs)	Pathogenic
965003	NM_000969.5(RPL5):c.634dup (p.Met212fs)	Pathogenic
1338679	NM_000969.5(RPL5):c.506del (p.Gly169fs)	Likely pathogenic
2033977	NM_000969.5(RPL5):c.74-2del	Likely pathogenic
4077472	NM_000969.5(RPL5):c.114dup (p.Gln39fs)	Likely pathogenic

SpliceAI

780 predictions. Top by Δscore:

Variant	Effect	Δscore
1:92832113:GGATG:G	donor_gain	1.0000
1:92832114:GATGG:G	donor_gain	1.0000
1:92832118:G:GA	donor_loss	1.0000
1:92833543:A:AG	acceptor_gain	1.0000
1:92833543:AGAG:A	acceptor_gain	1.0000
1:92833544:G:GC	acceptor_gain	1.0000
1:92833544:GA:G	acceptor_gain	1.0000
1:92833544:GAGG:G	acceptor_gain	1.0000
1:92833656:GTCAG:G	donor_gain	1.0000
1:92833659:AGGT:A	donor_loss	1.0000
1:92833661:G:GG	donor_gain	1.0000
1:92833661:GTA:G	donor_loss	1.0000
1:92833662:T:A	donor_loss	1.0000
1:92834777:A:AG	acceptor_gain	1.0000
1:92834777:AGATT:A	acceptor_gain	1.0000
1:92834778:G:GC	acceptor_gain	1.0000
1:92834778:GAT:G	acceptor_gain	1.0000
1:92834778:GATT:G	acceptor_gain	1.0000
1:92834778:GATTG:G	acceptor_gain	1.0000
1:92834909:GCAGG:G	donor_gain	1.0000
1:92834912:GG:G	donor_gain	1.0000
1:92834913:GG:G	donor_gain	1.0000
1:92834913:GGTA:G	donor_loss	1.0000
1:92836188:A:AG	acceptor_gain	1.0000
1:92836189:G:GG	acceptor_gain	1.0000
1:92836189:GC:G	acceptor_gain	1.0000
1:92836189:GCT:G	acceptor_gain	1.0000
1:92836189:GCTT:G	acceptor_gain	1.0000
1:92836189:GCTTC:G	acceptor_gain	1.0000
1:92836390:CAG:C	donor_gain	1.0000

AlphaMissense

1971 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:92833429:G:C	R15T	1.000
1:92833429:G:T	R15I	1.000
1:92833430:A:C	R15S	1.000
1:92833430:A:T	R15S	1.000
1:92833450:G:C	R22T	1.000
1:92833450:G:T	R22I	1.000
1:92833451:A:C	R22S	1.000
1:92833451:A:T	R22S	1.000
1:92833547:G:C	G26R	1.000
1:92833548:G:A	G26D	1.000
1:92833554:C:T	T28I	1.000
1:92833556:G:C	D29H	1.000
1:92833557:A:T	D29V	1.000
1:92833566:C:A	A32D	1.000
1:92833578:T:C	L36S	1.000
1:92833578:T:G	L36W	1.000
1:92833588:A:C	Q39H	1.000
1:92833588:A:T	Q39H	1.000
1:92833594:A:C	K41N	1.000
1:92833594:A:T	K41N	1.000
1:92833598:A:G	K43E	1.000
1:92833600:A:C	K43N	1.000
1:92833600:A:T	K43N	1.000
1:92833601:T:C	Y44H	1.000
1:92833613:A:G	K48E	1.000
1:92833615:A:C	K48N	1.000
1:92833615:A:T	K48N	1.000
1:92833616:T:G	Y49D	1.000
1:92833619:A:G	R50G	1.000
1:92833619:A:T	R50W	1.000

dbSNP variants (sampled 300 via entrez): RS1000305053 (1:92841100 T>C), RS1001095608 (1:92832052 C>A,T), RS1001216773 (1:92831510 A>G), RS1001445033 (1:92831874 T>A,C), RS1001520666 (1:92835501 A>G), RS1002143016 (1:92841585 G>A), RS1002481330 (1:92831224 T>C), RS1002526880 (1:92837220 C>T), RS1002840787 (1:92840203 G>T), RS1003097504 (1:92831917 C>A,T), RS1003116038 (1:92834121 G>A), RS1003193439 (1:92842005 T>G), RS1003246317 (1:92842284 G>T), RS1003533956 (1:92838774 A>G), RS1003648466 (1:92838502 G>A)

Disease associations

OMIM: gene MIM:603634 | disease phenotypes: MIM:105650, MIM:612561

GenCC curated gene-disease

Disease	Classification	Inheritance
Diamond-Blackfan anemia 6	Definitive	Autosomal dominant
Diamond-Blackfan anemia	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Diamond-Blackfan anemia 6	Definitive	AD

Mondo (3): Diamond-Blackfan anemia (MONDO:0015253), Diamond-Blackfan anemia 6 (MONDO:0012937), Diamond-Blackfan anemia 1 (MONDO:0007110)

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

HPO phenotypes

72 total (30 of 72 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000047	Hypospadias
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:0000193	Bifid uvula
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000234	Abnormality of the head
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000519	Developmental cataract
HP:0000912	Sprengel anomaly
HP:0000980	Pallor
HP:0001087	Developmental glaucoma
HP:0001199	Triphalangeal thumb
HP:0001227	Abnormality of the thenar eminence
HP:0001254	Lethargy

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000062_2	Multiple sclerosis	8.000000e-06
GCST000425_2	Multiple sclerosis	3.000000e-06
GCST000817_165	Height	7.000000e-11
GCST007563_13	Allergic disease (asthma, hay fever or eczema)	7.000000e-09
GCST90002390_7	Mean corpuscular hemoglobin	4.000000e-12
GCST90002396_137	Mean reticulocyte volume	1.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
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
C538442	Aase Smith syndrome 2 (supp.)
C567302	Diamond-Blackfan Anemia 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066896 (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
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
6.06	Kd	862.5	nM	CHEMBL3752910
6.06	ED50	862.5	nM	CHEMBL3752910
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
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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149271: Binding affinity to human RPL5 incubated for 45 mins by Kinobead based pull down assay	kd	0.8625	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	4
sodium arsenite	affects cotreatment, increases abundance, affects binding, decreases reaction, decreases expression	3
Valproic Acid	decreases methylation, increases expression	2
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
beauvericin	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
trichostatin A	increases expression	1
hydroxyhydroquinone	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
phenanthrene	decreases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
epigallocatechin gallate	affects cotreatment, increases expression	1
chloropicrin	affects expression	1
enniatins	affects cotreatment, 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
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	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)

38 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
NCT00235391	PHASE3	COMPLETED	Expanded Access of Deferasirox to Patients With Congenital Disorders of Red Blood Cells and Chronic Iron Overload
NCT00001962	PHASE2	TERMINATED	A Study to Determine Whether Therapy With Daclizumab Will Benefit Patients With Bone Marrow Failure
NCT00011505	PHASE2	COMPLETED	Mobilization of Stem Cells With G-CSF for Collection From Patients With Diamond-Blackfan Anemia
NCT00301834	PHASE2	COMPLETED	Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
NCT00957931	PHASE2	COMPLETED	Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT02386267	PHASE2	UNKNOWN	L-leucine in Diamond Blackfan Anemia Patients
NCT02512679	PHASE2	TERMINATED	Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells
NCT03333486	PHASE2	TERMINATED	Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
NCT04099966	PHASE2	RECRUITING	AlloSCT for Malignant and Non-malignant Hematologic Diseases Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion
NCT04965597	PHASE2	COMPLETED	Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
NCT01586455	PHASE1	COMPLETED	Human Placental-Derived Stem Cell Transplantation
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00176852	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Hemoglobinopathy
NCT00176878	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Bone Marrow Failure Syndromes
NCT00305708	PHASE1/PHASE2	COMPLETED	Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
NCT01362595	PHASE1/PHASE2	COMPLETED	Pilot Phase I/II Study of Amino Acid Leucine in Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia
NCT01419704	PHASE1/PHASE2	WITHDRAWN	Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
NCT01464164	PHASE1/PHASE2	TERMINATED	Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia
NCT01966367	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT02065869	PHASE1/PHASE2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03653338	PHASE1/PHASE2	RECRUITING	T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias
NCT03733249	PHASE1/PHASE2	TERMINATED	Long Term Follow-up Study for Patients Enrolled on the BP-004 Clinical Study
NCT03966053	PHASE1/PHASE2	TERMINATED	The Use of Trifluoperazine in Transfusion Dependent DBA
NCT00027274	Not specified	RECRUITING	Cancer in Inherited Bone Marrow Failure Syndromes
NCT00244010	Not specified	COMPLETED	Partially Matched Stem Cell Transplantation for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias
NCT00290628	Not specified	TERMINATED	Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer
NCT01114776	Not specified	COMPLETED	Multi-Center Study of Iron Overload: Pilot Study
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT01758042	Not specified	COMPLETED	Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders
NCT01913548	Not specified	COMPLETED	Multi-Center Study of Iron Overload: Survey Study (MCSIO)
NCT02179359	Not specified	TERMINATED	Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT07186179	Not specified	RECRUITING	Mobilization of CD34+ Peripheral Blood Stem Cells in Patients With Diamond Blackfan Anemia Syndrome (DBAS)