RPS27A

Summary

RPS27A (ribosomal protein S27a, HGNC:10417) is a protein-coding gene on chromosome 2p16.1, encoding Ubiquitin-ribosomal protein eS31 fusion protein (P62979). Exists either covalently attached to another protein, or free (unanchored). It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Ubiquitin, a highly conserved protein that has a major role in targeting cellular proteins for degradation by the 26S proteosome, is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin fused to an unrelated protein. This gene encodes a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein S27a at the C terminus. When expressed in yeast, the protein is post-translationally processed, generating free ubiquitin monomer and ribosomal protein S27a. Ribosomal protein S27a is a component of the 40S subunit of the ribosome and belongs to the S27AE family of ribosomal proteins. It contains C4-type zinc finger domains and is located in the cytoplasm. Pseudogenes derived from this gene are present in the genome. As with ribosomal protein S27a, ribosomal protein L40 is also synthesized as a fusion protein with ubiquitin; similarly, ribosomal protein S30 is synthesized as a fusion protein with the ubiquitin-like protein fubi. Multiple alternatively spliced transcript variants that encode the same proteins have been identified.

Source: NCBI Gene 6233 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 24 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_002954

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10417
Approved symbol	RPS27A
Name	ribosomal protein S27a
Location	2p16.1
Locus type	gene with protein product
Status	Approved
Aliases	UBCEP80, Uba80, S27A, eS31
Ensembl gene	ENSG00000143947
Ensembl biotype	protein_coding
OMIM	191343
Entrez	6233

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 28 protein_coding, 6 retained_intron

ENST00000272317, ENST00000402285, ENST00000404735, ENST00000449323, ENST00000463185, ENST00000468810, ENST00000471772, ENST00000478196, ENST00000494756, ENST00000495843, ENST00000859839, ENST00000859840, ENST00000859841, ENST00000859842, ENST00000859843, ENST00000939236, ENST00000939237, ENST00000939238, ENST00000939239, ENST00000939240, ENST00000939241, ENST00000939242, ENST00000939243, ENST00000939244, ENST00000939245, ENST00000939246, ENST00000939247, ENST00000939248, ENST00000939249, ENST00000939250, ENST00000939251, ENST00000939252, ENST00000966020, ENST00000966021

RefSeq mRNA: 3 — MANE Select: NM_002954 NM_001135592, NM_001177413, NM_002954

CCDS: CCDS33202

Canonical transcript exons

ENST00000272317 — 6 exons

Exon	Start	End
ENSE00001035837	55234831	55234962
ENSE00001911348	55235428	55235853
ENSE00001925745	55232688	55232708
ENSE00003499268	55233363	55233417
ENSE00003554742	55232808	55232872
ENSE00003602280	55234119	55234204

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.2085 / max 923.9209, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20341	71.3203	1820
20340	5.2652	1568
20339	1.6230	996

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.88	gold quality
left ovary	UBERON:0002119	99.88	gold quality
endocervix	UBERON:0000458	99.87	gold quality
right uterine tube	UBERON:0001302	99.87	gold quality
right ovary	UBERON:0002118	99.87	gold quality
ganglionic eminence	UBERON:0004023	99.87	gold quality
ventricular zone	UBERON:0003053	99.86	gold quality
cortical plate	UBERON:0005343	99.86	gold quality
body of uterus	UBERON:0009853	99.86	gold quality
right lobe of thyroid gland	UBERON:0001119	99.84	gold quality
left lobe of thyroid gland	UBERON:0001120	99.84	gold quality
adenohypophysis	UBERON:0002196	99.84	gold quality
metanephros cortex	UBERON:0010533	99.84	gold quality
left uterine tube	UBERON:0001303	99.83	gold quality
ectocervix	UBERON:0012249	99.83	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.83	gold quality
mucosa of stomach	UBERON:0001199	99.82	gold quality
right lung	UBERON:0002167	99.82	gold quality
popliteal artery	UBERON:0002250	99.82	gold quality
descending thoracic aorta	UBERON:0002345	99.82	gold quality
tibial artery	UBERON:0007610	99.82	gold quality
body of pancreas	UBERON:0001150	99.81	gold quality
body of stomach	UBERON:0001161	99.81	gold quality
ascending aorta	UBERON:0001496	99.81	gold quality
thoracic aorta	UBERON:0001515	99.81	gold quality
calcaneal tendon	UBERON:0003701	99.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.81	gold quality
skin of abdomen	UBERON:0001416	99.80	gold quality
left coronary artery	UBERON:0001626	99.80	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.80	gold quality

Single-cell (SCXA)

Detected in 34 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	12005.81
E-CURD-88	yes	9148.44
E-MTAB-10042	yes	8874.23
E-CURD-122	yes	6777.17
E-MTAB-9221	yes	58.09
E-MTAB-6678	yes	44.49
E-CURD-112	yes	36.45
E-HCAD-35	yes	9.00
E-HCAD-1	no	9858.91
E-CURD-120	no	9732.77
E-MTAB-6701	no	9695.52
E-MTAB-8559	no	9400.18
E-MTAB-9467	no	9294.62
E-MTAB-8410	no	8503.00
E-MTAB-8322	no	8481.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, SP1

miRNA regulators (miRDB)

20 targeting RPS27A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-6759-3P	96.94	68.31	823

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 18)

• ubiquitin carboxyl extension protein 1 is overexpressed in prostate cancer (PMID:15647830)
• S27a plays a non-redundant role in mediating p53 activation in response to ribosomal stress via interplaying with MDM2. (PMID:21561866)
• Gene expression profiles showed that RPS27A was down-regulated in epidermolysis bullosa subtypes. (PMID:22716248)
• Knockdown of RPS27a inhibits the proliferation, induces cell cycle arrest and potentiates the effect of imatinib on apoptosis of K562 cells. (PMID:24680683)
• RPS27A expression was found to have a weak inverse correlation with overexpression of multifunctional protein YB-1 in HCC tissues. (PMID:24833360)
• RPS27a appears to be a novel stress sensor in the cell which amplifies p53 response to arrest cell cycle. (PMID:25592822)
• Imatinib-resistant K562/G01 cells expressed significantly higher levels of STAT3 and RPS27a compared with those of K562 cells. (PMID:26942564)
• the full-length cDNA sequence of MMSA-8 was cloned in MM and it was hypothesized that MMSA-8 is MM-associated RPS27A transcript variant 1 (PMID:28498418)
• RPS27a enhances viral LMP1-mediated proliferation and invasion, suggesting that RPS27a interacts with LMP1 and stabilizes it by suppressing proteasome-mediated ubiquitination. (PMID:28735865)
• this study shows that interactions of antisera to different Chlamydia and Chlamydophila species with the ribosomal protein RPS27a correlate with impaired protein synthesis in a human choroid plexus papilloma cell line (PMID:28913776)
• MTG1 establishes a quality control checkpoint in mitoribosome assembly. In conclusion, MTG1 controls mitochondrial translation by coupling mtLSU assembly with intersubunit bridge formation using the intrinsic GEF activity acquired by the mtSSU through mS27, a unique occurrence in translational systems. (PMID:30085276)
• USP16 counteracts mono-ubiquitination of RPS27a and promotes maturation of the 40S ribosomal subunit. (PMID:32129764)
• The Ubiquitin Gene Expression Pattern and Sensitivity to UBB and UBC Knockdown Differentiate Primary 23132/87 and Metastatic MKN45 Gastric Cancer Cells. (PMID:32751694)
• Rps27a might act as a controller of microglia activation in triggering neurodegenerative diseases. (PMID:32941527)
• PICT1 is critical for regulating the Rps27a-Mdm2-p53 pathway by microtubule polymerization inhibitor against cervical cancer. (PMID:34166715)
• Multifaceted functions of RPS27a: An unconventional ribosomal protein. (PMID:36580426)
• RPS27a and RPL40, Which Are Produced as Ubiquitin Fusion Proteins, Are Not Essential for p53 Signalling. (PMID:37371478)
• UBA80 and UBA52 fine-tune RNF168-dependent histone ubiquitination and DNA repair. (PMID:37451480)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rps27a	ENSMUSG00000020460
rattus_norvegicus	Rps27a	ENSRNOG00000004426
rattus_norvegicus	Rps27a-ps2	ENSRNOG00000051047

Paralogs (10): UBL4A (ENSG00000102178), NEDD8 (ENSG00000129559), UBC (ENSG00000150991), UBB (ENSG00000170315), ZFAND4 (ENSG00000172671), UBL4B (ENSG00000186150), ISG15 (ENSG00000187608), ANKUB1 (ENSG00000206199), UBD (ENSG00000213886), UBA52 (ENSG00000221983)

Protein

Protein identifiers

Ubiquitin-ribosomal protein eS31 fusion protein — P62979 (reviewed: P62979)

Alternative names: Ubiquitin carboxyl extension protein 80

All UniProt accessions (3): P62979, B2RDW1, J3QTR3

UniProt curated annotations — full annotation on UniProt →

Function. Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. Component of the 40S subunit of the ribosome. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.

Subunit / interactions. Part of the 40S ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.

Subcellular location. Cytoplasm. Nucleus. Nucleolus Cytoplasm.

Post-translational modifications. Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy. Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30. Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones. (Microbial infection) Mono-ADP-ribosylated at Thr-66 by the C.violaceum CteC virulence factor. ADP-ribosylation causes the shutdown of polyubiquitin synthesis and disrupts the recognition and reversal of polyubiquitin. Monoubiquitinated at Lys-107 and Lys-113 by RNF25 in response to ribosome collisions (ribosome stalling): ubiquitination promotes subsequent activation of RNF14, leading to EEF1A1 ubiquitination and degradation and rescue of stalled ribosomes. Deubiquitination at Lys-113 by USP16 is required for maturation of the 40S ribosomal complex.

Miscellaneous. Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins eL40 and eS31, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains. For a better understanding, features related to ubiquitin are only indicated for the first chain.

Similarity. In the N-terminal section; belongs to the ubiquitin family. In the C-terminal section; belongs to the eukaryotic ribosomal protein eS31 family.

RefSeq proteins (3): NP_001129064, NP_001170884, NP_002945* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR002906	Ribosomal_eS31	Domain
IPR011332	Ribosomal_zn-bd	Homologous_superfamily
IPR019954	Ubiquitin_CS	Conserved_site
IPR019956	Ubiquitin_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR038582	Ribosomal_eS31_euk_sf	Homologous_superfamily
IPR050158	Ubiquitin_ubiquitin-like	Family

Pfam: PF00240, PF01599

UniProt features (59 total): strand 16, mutagenesis site 13, cross-link 10, modified residue 6, helix 4, site 3, chain 2, turn 2, domain 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

263 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3NHE	X-RAY DIFFRACTION	1.26
6SQO	X-RAY DIFFRACTION	1.41
7F0N	X-RAY DIFFRACTION	1.6
8GLP	ELECTRON MICROSCOPY	1.67
3NS8	X-RAY DIFFRACTION	1.71
3N32	X-RAY DIFFRACTION	1.79
6SQS	X-RAY DIFFRACTION	1.83
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
5WVO	X-RAY DIFFRACTION	2
3PHW	X-RAY DIFFRACTION	2
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
7R4X	ELECTRON MICROSCOPY	2.15
8HTF	X-RAY DIFFRACTION	2.15
6SQR	X-RAY DIFFRACTION	2.18
3AXC	X-RAY DIFFRACTION	2.19
3NOB	X-RAY DIFFRACTION	2.19
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8HTC	X-RAY DIFFRACTION	2.2
8YOP	ELECTRON MICROSCOPY	2.2
9O3V	ELECTRON MICROSCOPY	2.2
9O3Y	ELECTRON MICROSCOPY	2.2
4R62	X-RAY DIFFRACTION	2.28
8G5Y	ELECTRON MICROSCOPY	2.29
9S3D	ELECTRON MICROSCOPY	2.32
9RPV	ELECTRON MICROSCOPY	2.35
9S3B	ELECTRON MICROSCOPY	2.38
6KG6	X-RAY DIFFRACTION	2.39

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62979-F1	89.65	0.75

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 54 (interacts with activating enzyme); 68 (essential for function); 72 (interacts with activating enzyme)

Post-translational modifications (16): 76, 104, 113, 152, 6, 11, 27, 29, 33, 48, 63, 76, 107, 113, 65, 66

Mutagenesis-validated functional residues (13):

Position	Phenotype
48	no effect on hltf-mediated polyubiquitination of pcna.
63	abolishes hltf-mediated polyubiquitination of pcna.
65	prevents phosphorylation in case of mitophagy. impaired translocation of prkn to mitochondria.
65	phosphomimetic mutant that binds and activates prkn.
65	phosphomimetic mutant that can recruit prkn to mitochondria.
68	loss of dtx3l-mediated polyubiquitination of histone h3 and h4.
72	no effect on adp-ribosylation.
72	no effect on adp-ribosylation, when associated with k-74.
74	no effect on adp-ribosylation.
74	no effect on adp-ribosylation, when associated with k-72.
76	loss of adp-ribosylation.
107	abolished monoubiquitination by rnf25, leading to impaired ability to rescue stalled ribosomes; when associated with r-1
113	abolished monoubiquitination by rnf25, leading to impaired ability to rescue stalled ribosomes; when associated with r-1

Function

Pathways and Gene Ontology

Reactome pathways

433 pathways

ID	Pathway
R-HSA-110312	Translesion synthesis by REV1
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex
R-HSA-110320	Translesion Synthesis by POLH
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1236382	Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1253288	Downregulation of ERBB4 signaling
R-HSA-1295596	Spry regulation of FGF signaling
R-HSA-1358803	Downregulation of ERBB2:ERBB3 signaling
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-156902	Peptide chain elongation
R-HSA-162588	Budding and maturation of HIV virion
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-168927	TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-174048	APC/C:Cdc20 mediated degradation of Cyclin B
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-174113	SCF-beta-TrCP mediated degradation of Emi1
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-174490	Membrane binding and targetting of GAG proteins
R-HSA-175474	Assembly Of The HIV Virion
R-HSA-179409	APC-Cdc20 mediated degradation of Nek2A
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-180534	Vpu mediated degradation of CD4
R-HSA-180585	Vif-mediated degradation of APOBEC3G
R-HSA-182971	EGFR downregulation

MSigDB gene sets: 562 (showing top): REACTOME_TRAF6_MEDIATED_INDUCTION_OF_TAK1_COMPLEX_WITHIN_TLR4_COMPLEX, REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_CYTOPLASMIC_TRANSLATION, REACTOME_ENDOSOMAL_SORTING_COMPLEX_REQUIRED_FOR_TRANSPORT_ESCRT, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_APC_C_CDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, REACTOME_ADAPTIVE_IMMUNE_SYSTEM

GO Biological Process (4): cytoplasmic translation (GO:0002181), translation (GO:0006412), protein ubiquitination (GO:0016567), modification-dependent protein catabolic process (GO:0019941)

GO Molecular Function (7): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), zinc ion binding (GO:0008270), protein tag activity (GO:0031386), ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (21): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), endocytic vesicle membrane (GO:0030666), vesicle (GO:0031982), small-subunit processome (GO:0032040), synapse (GO:0045202), extracellular exosome (GO:0070062), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-22 pathways:

Category	Pathways
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	2
DNA Damage Bypass	1
Downstream signaling events of B Cell Receptor (BCR)	1
Antimicrobial mechanism of IFN-stimulated genes	1
Cellular response to hypoxia	1
Signaling by Ligand-Responsive EGFR Variants in Cancer	1
Antigen processing-Cross presentation	1
Signaling by ERBB4	1
Negative regulation of FGFR1 signaling	1
Negative regulation of FGFR2 signaling	1
Negative regulation of FGFR3 signaling	1
Negative regulation of FGFR4 signaling	1
Downregulation of ERBB2 signaling	1
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
ribosome	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
intracellular membraneless organelle	2
cytoplasm	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
protein modification by small protein conjugation	1
protein catabolic process	1
protein modification process	1
modification-dependent macromolecule catabolic process	1
nucleic acid binding	1
structural molecule activity	1
transition metal ion binding	1
molecular tag activity	1
ubiquitin-like protein ligase binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
mitochondrial membrane	1
organelle outer membrane	1
endomembrane system	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
endosome	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

311 interactions, top by confidence:

A	B	Type	Score
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
RPS27A	DAZAP2	psi-mi:“MI:0915”(physical association)	0.780
DAZAP2	RPS27A	psi-mi:“MI:0915”(physical association)	0.780
UBAC1	UBB	psi-mi:“MI:0914”(association)	0.740
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
PSMB2	PSMD11	psi-mi:“MI:0914”(association)	0.730
EPN1	PHGDH	psi-mi:“MI:0914”(association)	0.710
MYO6	GIPC1	psi-mi:“MI:0914”(association)	0.690
RPS27A	RNF11	psi-mi:“MI:0915”(physical association)	0.670
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPS27A	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.560
CALCOCO2	RPS27A	psi-mi:“MI:0915”(physical association)	0.560
RPS27A	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
RPS27A	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
RPS27A	FAM168A	psi-mi:“MI:0915”(physical association)	0.560
RPS27A	PLSCR4	psi-mi:“MI:0915”(physical association)	0.560
RPS27A	LITAF	psi-mi:“MI:0915”(physical association)	0.560
RPS27A	MTURN	psi-mi:“MI:0915”(physical association)	0.560
RPS27A	DESI1	psi-mi:“MI:0915”(physical association)	0.560
RPS27A	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
RAD23A	RPS27A	psi-mi:“MI:0915”(physical association)	0.560
EPN3	RPS27A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (702): DAZAP2 (Two-hybrid), CALCOCO2 (Two-hybrid), RPS27A (Affinity Capture-MS), RPS27A (Affinity Capture-MS), RPS27A (Affinity Capture-MS), RPS27A (Affinity Capture-MS), RPS27A (Affinity Capture-MS), RPS27A (Affinity Capture-MS), UBA52 (Co-fractionation), RPS27A (Synthetic Growth Defect), RPS27A (Reconstituted Complex), RPS27A (Affinity Capture-MS), RPS27A (Affinity Capture-MS), RPS27A (Affinity Capture-MS), RPS27A (Affinity Capture-MS)

ESM2 similar proteins: G1SK22, P05759, P0C016, P0C273, P0C275, P0C276, P0C8R3, P0CG86, P0CG87, P0CH10, P0CH11, P0DJ25, P0DXC2, P14795, P14797, P14799, P15357, P21899, P27923, P29504, P31753, P33190, P47905, P49633, P51431, P59232, P59233, P59271, P59272, P62978, P62979, P62980, P62981, P62982, P62983, P62984, P62986, P62987, P62992, P63048

Diamond homologs: A0B8S9, A0RUP3, A2SR71, A4FZ57, A6US53, A6VJ78, A9A217, A9A6I9, B0R6Y1, C5A443, G1SK22, O26368, O29152, P05759, P0C016, P0C8R3, P0CG86, P0CG87, P14797, P14799, P15357, P27923, P31753, P37164, P37165, P47905, P51431, P54031, P61238, P61239, P61240, P62978, P62979, P62980, P62981, P62982, P62983, P62992, P68200, P69061

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
USP7	“up-regulates quantity”	RPS27A	cleavage
USP9X	“up-regulates quantity”	RPS27A	cleavage
UCHL3	“up-regulates quantity”	RPS27A	cleavage
RPS27A	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 206 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
Antigen processing: Ub, ATP-independent proteasomal degradation	9	34.7×	4e-11
Constitutive Signaling by EGFRvIII	5	24.1×	2e-05
AUF1 (hnRNP D0) binds and destabilizes mRNA	14	23.5×	1e-13
Degradation of AXIN	14	23.5×	1e-13
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	6	23.1×	2e-06
Signaling by ERBB2 ECD mutants	5	22.7×	2e-05
Regulation of activated PAK-2p34 by proteasome mediated degradation	12	22.6×	7e-12
Vpu mediated degradation of CD4	12	21.5×	1e-11

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	6	11.0×	5e-03
autophagosome assembly	8	9.4×	1e-03
MAPK cascade	10	8.0×	4e-04
proteasome-mediated ubiquitin-dependent protein catabolic process	15	4.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

902 predictions. Top by Δscore:

Variant	Effect	Δscore
2:55232106:G:GT	donor_gain	1.0000
2:55232109:G:GG	donor_gain	1.0000
2:55232800:A:AG	acceptor_gain	1.0000
2:55232801:A:G	acceptor_gain	1.0000
2:55232806:A:AC	acceptor_loss	1.0000
2:55232806:AGGT:A	acceptor_gain	1.0000
2:55232807:GGTG:G	acceptor_gain	1.0000
2:55232869:CGAG:C	donor_loss	1.0000
2:55232872:GG:G	donor_loss	1.0000
2:55232873:GTAC:G	donor_loss	1.0000
2:55233414:G:GT	donor_gain	1.0000
2:55234110:T:TA	acceptor_gain	1.0000
2:55234114:A:AG	acceptor_gain	1.0000
2:55234114:ATTAG:A	acceptor_gain	1.0000
2:55234116:TA:T	acceptor_loss	1.0000
2:55234117:A:AG	acceptor_gain	1.0000
2:55234117:AG:A	acceptor_gain	1.0000
2:55234118:G:A	acceptor_gain	1.0000
2:55234118:G:GT	acceptor_gain	1.0000
2:55234118:GGA:G	acceptor_gain	1.0000
2:55234118:GGAA:G	acceptor_gain	1.0000
2:55234118:GGAAT:G	acceptor_gain	1.0000
2:55234173:G:GT	donor_gain	1.0000
2:55234200:AAAAG:A	donor_loss	1.0000
2:55234203:AGGTC:A	donor_loss	1.0000
2:55234205:G:C	donor_loss	1.0000
2:55234217:G:T	donor_gain	1.0000
2:55234823:A:AG	acceptor_gain	1.0000
2:55234824:T:G	acceptor_gain	1.0000
2:55234826:A:AG	acceptor_gain	1.0000

AlphaMissense

1029 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:55232834:T:C	F4L	1.000
2:55232836:C:A	F4L	1.000
2:55232836:C:G	F4L	1.000
2:55232847:T:A	L8H	1.000
2:55232852:G:A	G10R	1.000
2:55232852:G:C	G10R	1.000
2:55232852:G:T	G10W	1.000
2:55232853:G:A	G10E	1.000
2:55232853:G:T	G10V	1.000
2:55232868:T:C	L15P	1.000
2:55233382:T:A	I23K	1.000
2:55233395:G:C	K27N	1.000
2:55233395:G:T	K27N	1.000
2:55234137:A:C	Q41P	1.000
2:55234138:G:C	Q41H	1.000
2:55234138:G:T	Q41H	1.000
2:55234140:G:C	R42T	1.000
2:55234141:A:C	R42S	1.000
2:55234141:A:T	R42S	1.000
2:55234143:T:A	L43Q	1.000
2:55234143:T:C	L43P	1.000
2:55234146:T:A	I44N	1.000
2:55234148:T:A	F45I	1.000
2:55234148:T:C	F45L	1.000
2:55234149:T:C	F45S	1.000
2:55234150:T:A	F45L	1.000
2:55234150:T:G	F45L	1.000
2:55234154:G:C	G47R	1.000
2:55234154:G:T	G47C	1.000
2:55234155:G:A	G47D	1.000

dbSNP variants (sampled 300 via entrez): RS1000042922 (2:55233105 G>A), RS1000074323 (2:55233227 A>G,T), RS1000149447 (2:55232796 C>T), RS1000999801 (2:55233560 T>C), RS1001042669 (2:55232502 G>C), RS1001708874 (2:55231980 A>C), RS1001713156 (2:55233922 A>C,G), RS1001823387 (2:55231757 C>T), RS1003328195 (2:55235207 G>A,C), RS1003404414 (2:55230634 G>A), RS1003425214 (2:55234993 A>C,G,T), RS1004174164 (2:55231108 G>A,C,T), RS1004270138 (2:55232976 T>C), RS1004525678 (2:55230832 T>C), RS1005085942 (2:55231774 C>G)

Disease associations

OMIM: gene MIM:191343 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL4523597 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

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

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

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

ChEMBL bioactivities

47 potent at pChembl≥5 of 51 total, top 46 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
6.12	IC50	760	nM	MOLIBRESIB
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	IC50	900	nM	CHEMBL4126894
6.05	IC50	900	nM	CHEMBL4126496
6.04	IC50	920	nM	CHEMBL4554909
5.97	IC50	1060	nM	CHEMBL4128388
5.89	IC50	1290	nM	CHEMBL4130157
5.86	IC50	1370	nM	CHEMBL4107559
5.84	IC50	1440	nM	CHEMBL4108338
5.81	IC50	1540	nM	CHEMBL4534859
5.76	IC50	1730	nM	CHEMBL4534859
5.69	IC50	2050	nM	CHEMBL4566239
5.68	IC50	2080	nM	CHEMBL4446635
5.66	IC50	2210	nM	CHEMBL4446635
5.66	EC50	2200	nM	CHEMBL4464929
5.64	IC50	2270	nM	CHEMBL4533299
5.63	IC50	2330	nM	CHEMBL4566239
5.62	IC50	2380	nM	CHEMBL4128388
5.58	IC50	2630	nM	CHEMBL4128250
5.55	IC50	2820	nM	CHEMBL4127458
5.53	IC50	2970	nM	CHEMBL4127311
5.51	IC50	3080	nM	CHEMBL4126072
5.46	IC50	3500	nM	CHEMBL4525277
5.44	IC50	3630	nM	CHEMBL4469712
5.39	IC50	4100	nM	CHEMBL4128560
5.37	IC50	4300	nM	CHEMBL4127016
5.36	IC50	4380	nM	CHEMBL4527910
5.16	IC50	7000	nM	CHEMBL4109308
5.13	IC50	7400	nM	CHLORAMPHENICOL SULFATE SALT
5.09	IC50	8040	nM	CHEMBL4128250
5.08	IC50	8370	nM	CHEMBL4128250
5.03	IC50	9320	nM	CHEMBL4127016
5.03	IC50	9240	nM	CHEMBL4128560

PubChem BioAssay actives

47 with measured affinity, of 212 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178957: Inhibition of RPS27A (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.7600	uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylpiperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.9200	uM
N-isoquinolin-1-yl-4-(1-methylpyrazol-4-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	1.0600	uM
N-isoquinolin-1-yl-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	1.5400	uM
N-(3-methyl-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.0500	uM
N-(3-chloro-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	2.0800	uM
N-(5,8-dihydroisoquinolin-1-yl)-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1584424: Inhibition of human 80S ribosome-mediated PCSK9 translation expressed in CHO-K1 cells assessed as reduction in PCSK9 secretion	ec50	2.2000	uM
N-isoquinolin-1-yl-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.6300	uM
N-(3-chloro-2-pyridinyl)-4-(6-methylpyrazin-2-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.8200	uM
N-(3-chloro-2-pyridinyl)-4-[6-(dimethylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.9700	uM
N-(3-chloro-2-pyridinyl)-4-[6-(methylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	3.0800	uM
N-isoquinolin-1-yl-4-(6-methyl-1,2-benzoxazol-3-yl)-N-[(3R)-piperidin-3-yl]piperazine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	3.5000	uM
N-(3-methylpyrazin-2-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	3.6300	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-6-(triazolo[4,5-b]pyridin-3-yl)pyridine-3-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.1000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazin-2-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.3000	uM
4-(2-fluorophenyl)-N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	4.3800	uM
2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide;sulfuric acid	717551: Inhibition of mitochondrial ribosome-mediated protein synthesis in human HeLa cells assessed as {35S]methionine incorporation by autoradiography	ic50	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Arsenic	decreases expression, increases abundance, increases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, increases methylation	2
FR900359	decreases phosphorylation	1
moringin	increases expression	1
dicrotophos	decreases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
gossypol acetic acid	increases expression	1
arsenic trichloride	increases abundance, affects cotreatment, decreases expression	1
dinophysistoxin 1	increases expression	1
arsenic disulfide	decreases expression	1
azoxystrobin	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
azaspiracid	increases expression	1
K 7174	decreases expression	1
fenpyroximate	increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
pyrimidifen	increases expression	1
pyrachlostrobin	increases expression	1
enzalutamide	affects expression	1
picoxystrobin	increases expression	1
MT19c compound	increases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1

ChEMBL screening assays

96 unique, capped per target: 96 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1920845	Binding	Induction of ribosome to readthrough in human A-T lymphoblastoid cells assessed as ATM ser1981 autophosphorylation at 30 uM after 4 days by PTT-ELISA assay	Synthesis and evaluation of compounds that induce readthrough of premature termination codons. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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