RPS14

Summary

RPS14 (ribosomal protein S14, HGNC:10387) is a protein-coding gene on chromosome 5q33.1, encoding Small ribosomal subunit protein uS11 (P62263). Component of the small ribosomal subunit. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S11P family of ribosomal proteins. It is located in the cytoplasm. Transcript variants utilizing alternative transcription initiation sites have been described in the literature. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. In Chinese hamster ovary cells, mutations in this gene can lead to resistance to emetine, a protein synthesis inhibitor. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 6208 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 19 total
• Phenotypes (HPO): 24
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_005617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10387
Approved symbol	RPS14
Name	ribosomal protein S14
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	EMTB, S14, uS11
Ensembl gene	ENSG00000164587
Ensembl biotype	protein_coding
OMIM	130620
Entrez	6208

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000312037, ENST00000401695, ENST00000407193, ENST00000518139, ENST00000519690, ENST00000519855, ENST00000521466, ENST00000642507, ENST00000866543, ENST00000866544, ENST00000866545, ENST00000922452, ENST00000922453, ENST00000922454, ENST00000922455, ENST00000922456, ENST00000922457, ENST00000922458, ENST00000922459, ENST00000922460, ENST00000922461, ENST00000922462, ENST00000922463, ENST00000922464, ENST00000922465, ENST00000922466, ENST00000922467, ENST00000964173

RefSeq mRNA: 3 — MANE Select: NM_005617 NM_001025070, NM_001025071, NM_005617

CCDS: CCDS4307

Canonical transcript exons

ENST00000407193 — 5 exons

Exon	Start	End
ENSE00001085690	150446802	150446963
ENSE00001085694	150447585	150447735
ENSE00001198518	150449703	150449739
ENSE00001914673	150442635	150444353
ENSE00003646432	150445609	150445685

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.9822 / max 855.6028, expressed in 1826 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64246	56.5495	1821
64245	9.0602	1672
64247	4.4921	1632
64244	2.8804	983

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.97	gold quality
adult organism	UBERON:0007023	99.96	gold quality
skin of hip	UBERON:0001554	99.95	gold quality
superficial temporal artery	UBERON:0001614	99.95	gold quality
caput epididymis	UBERON:0004358	99.95	gold quality
corpus epididymis	UBERON:0004359	99.94	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.94	gold quality
urethra	UBERON:0000057	99.93	gold quality
penis	UBERON:0000989	99.93	gold quality
nipple	UBERON:0002030	99.93	gold quality
tendon of biceps brachii	UBERON:0008188	99.93	gold quality
epididymis	UBERON:0001301	99.92	gold quality
parotid gland	UBERON:0001831	99.91	gold quality
cauda epididymis	UBERON:0004360	99.91	gold quality
monocyte	CL:0000576	99.90	gold quality
mononuclear cell	CL:0000842	99.90	gold quality
oral cavity	UBERON:0000167	99.90	gold quality
synovial joint	UBERON:0002217	99.90	gold quality
trachea	UBERON:0003126	99.90	gold quality
leukocyte	CL:0000738	99.89	gold quality
mammalian vulva	UBERON:0000997	99.89	gold quality
seminal vesicle	UBERON:0000998	99.89	gold quality
pericardium	UBERON:0002407	99.89	gold quality
trabecular bone tissue	UBERON:0002483	99.89	gold quality
lower lobe of lung	UBERON:0008949	99.89	gold quality
pylorus	UBERON:0001166	99.88	gold quality
epithelium of nasopharynx	UBERON:0001951	99.88	gold quality
colonic mucosa	UBERON:0000317	99.87	gold quality
cardia of stomach	UBERON:0001162	99.87	gold quality
germinal epithelium of ovary	UBERON:0001304	99.87	gold quality

Single-cell (SCXA)

Detected in 43 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	8594.22
E-MTAB-9067	yes	6960.61
E-CURD-122	yes	113.31
E-MTAB-6678	yes	42.36
E-CURD-112	yes	41.29
E-MTAB-10042	yes	15.65
E-HCAD-35	yes	10.77
E-MTAB-9801	yes	6.09
E-GEOD-137537	yes	5.47
E-MTAB-5061	yes	4.02
E-CURD-98	no	9781.52
E-MTAB-9467	no	9711.31
E-CURD-55	no	9558.63
E-MTAB-6308	no	9295.14
E-MTAB-8322	no	9249.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, NR2F1, PPARA, SREBF1, THRA, THRB, USF1

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 18)

• results indicate that the 5q- syndrome is caused by a defect in RPS14 ribosomal protein function (PMID:18202658)
• low expression of RPS14 is not due to promoter hypermethylation, further supporting the haploinsufficiency model suggested by Ebert et al4 for the 5q- syndrome (PMID:18650472)
• Myelodysplactic syndrome patients with an intermediate-1 risk score and low RPS14 expression have a superior median overall survival compared to patients with high RPS14 expression. (PMID:19794090)
• Studied the methylation status of the RPS14 gene in 5q deletion (5q21.3q33.1) in 24 patients. In all, 21 of the 37 patients (57%) had copy number alterations. No homozygous losses or amplifications were observed. (PMID:20193850)
• observations in the patient setting support the importance of RPS14 in the pathogenesis of MDS with del(5q) (PMID:20491881)
• p53 accumulates selectively in the erythroid lineage in primary human hematopoietic progenitor cells after expression of shRNAs targeting RPS14, the ribosomal protein gene deleted in the 5q-syndrome, or RPS19. (PMID:21068437)
• Combined loss of miR-145 and RPS14 cooperates to alter erythroid-megakaryocytic differentiation in a manner similar to the 5q- syndrome. (PMID:21873545)
• RPS14 and RPS19 have distinct roles in regulating the MDM2-p53 feedback loop in response to ribosomal stress (PMID:22391559)
• Loss of RPS14 is associated with 5q-syndrome. (PMID:22430631)
• RPS14 stabilized and activated p53 by inhibiting HDM2-mediated p53 polyubiquitination and degradation (PMID:23246961)
• lower RPS14 predicts prolonged survival and possible response to lenalidomide in lower risk MDS patients. (PMID:23506134)
• Data indicate that RPS14 negates c-Myc functions by directly inhibiting its transcriptional activity and mediating its mRNA degradation via miRNA. (PMID:23775087)
• Patients with nonclassical Diamond Blackfan anemia and other hypoproliferative anemias may have somatically acquired 5q deletions with RPS14 haploinsufficiency (PMID:23943650)
• Partial silencing of RPS14 inhibits the proliferation of SKM-1, an acute myeloid leukemia cell line, and RPS14 negatively regulates p53 activation in SKM-1 cells. (PMID:24074450)
• L-leucine increases translation of RPS14 and LARP1 in erythroblasts from del(5q) myelodysplastic syndrome patients. (PMID:29903759)
• Integrated analyses of translatome and proteome identify the rules of translation selectivity in RPS14-deficient cells. (PMID:32327500)
• RPS14 promotes the development and progression of glioma via p53 signaling pathway. (PMID:36535509)
• Genome-wide functional integration identified MAZ-controlled RPS14 dysregulation in hepatocellular carcinoma. (PMID:38189915)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps14	ENSDARG00000036629
mus_musculus	Rps14	ENSMUSG00000024608
rattus_norvegicus	Rps14	ENSRNOG00000018774
rattus_norvegicus	LOC120101650	ENSRNOG00000031585
drosophila_melanogaster	RpS14a	FBGN0004403
drosophila_melanogaster	RpS14b	FBGN0004404
caenorhabditis_elegans		WBGENE00004483

Paralogs (1): MRPS11 (ENSG00000181991)

Protein

Protein identifiers

Small ribosomal subunit protein uS11 — P62263 (reviewed: P62263)

Alternative names: 40S ribosomal protein S14

All UniProt accessions (3): A0A2R8Y811, E5RH77, P62263

UniProt curated annotations — full annotation on UniProt →

Function. Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. 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. Component of the small 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.

Similarity. Belongs to the universal ribosomal protein uS11 family.

RefSeq proteins (3): NP_001020241, NP_001020242, NP_005608* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001971	Ribosomal_uS11	Family
IPR018102	Ribosomal_uS11_CS	Conserved_site
IPR036967	Ribosomal_uS11_sf	Homologous_superfamily

Pfam: PF00411

UniProt features (22 total): strand 7, helix 4, modified residue 3, cross-link 3, initiator methionine 1, chain 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

213 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8GLP	ELECTRON MICROSCOPY	1.67
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
7R4X	ELECTRON MICROSCOPY	2.15
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8YOP	ELECTRON MICROSCOPY	2.2
9O3V	ELECTRON MICROSCOPY	2.2
9O3Y	ELECTRON MICROSCOPY	2.2
8JDK	ELECTRON MICROSCOPY	2.26
8G5Y	ELECTRON MICROSCOPY	2.29
9S3D	ELECTRON MICROSCOPY	2.32
9RPV	ELECTRON MICROSCOPY	2.35
9S3B	ELECTRON MICROSCOPY	2.38
8K2C	ELECTRON MICROSCOPY	2.4
8XSX	ELECTRON MICROSCOPY	2.4
9SPF	ELECTRON MICROSCOPY	2.4
9SPI	ELECTRON MICROSCOPY	2.4
8JDL	ELECTRON MICROSCOPY	2.42
9S3C	ELECTRON MICROSCOPY	2.42
9QLO	ELECTRON MICROSCOPY	2.47
9P8B	ELECTRON MICROSCOPY	2.48
7XNY	ELECTRON MICROSCOPY	2.5
8JDJ	ELECTRON MICROSCOPY	2.5
9RUC	ELECTRON MICROSCOPY	2.5
8G60	ELECTRON MICROSCOPY	2.54
8IFE	ELECTRON MICROSCOPY	2.57
9P7D	ELECTRON MICROSCOPY	2.57

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62263-F1	89.99	0.77

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 (6): 16, 133, 139, 61, 63, 106

Function

Pathways and Gene Ontology

Reactome pathways

51 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-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72649	Translation initiation complex formation
R-HSA-72689	Formation of a pool of free 40S subunits
R-HSA-72695	Formation of the ternary complex, and subsequently, the 43S complex
R-HSA-72702	Ribosomal scanning and start codon recognition
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-72764	Eukaryotic Translation Termination
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-9735869	SARS-CoV-1 modulates host translation machinery
R-HSA-9754678	SARS-CoV-2 modulates host translation machinery
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-9954714	PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-156842	Eukaryotic Translation Elongation
R-HSA-1643685	Disease
R-HSA-168255	Influenza Infection
R-HSA-168273	Influenza Viral RNA Transcription and Replication
R-HSA-2262752	Cellular responses to stress
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-376176	Signaling by ROBO receptors

MSigDB gene sets: 338 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_MYELOID_CELL_HOMEOSTASIS, GNF2_TPT1, GCM_NPM1, GOBP_MATURATION_OF_SSU_RRNA, GOBP_ERYTHROCYTE_HOMEOSTASIS, HSIAO_HOUSEKEEPING_GENES, GOBP_RIBOSOME_ASSEMBLY, TGACCTY_ERR1_Q2, GOBP_TRANSLATION, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION

GO Biological Process (7): ribosomal small subunit assembly (GO:0000028), negative regulation of transcription by RNA polymerase II (GO:0000122), cytoplasmic translation (GO:0002181), translation (GO:0006412), erythrocyte differentiation (GO:0030218), maturation of SSU-rRNA (GO:0030490), ribosomal small subunit biogenesis (GO:0042274)

GO Molecular Function (4): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), mRNA 5’-UTR binding (GO:0048027), protein binding (GO:0005515)

GO Cellular Component (15): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), postsynaptic density (GO:0014069), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), small-subunit processome (GO:0032040), extracellular exosome (GO:0070062), nucleus (GO:0005634), ribosome (GO:0005840), synapse (GO:0045202), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Translation	2
rRNA processing in the nucleus and cytosol	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
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1
Signaling by ROBO receptors	1
Cellular response to starvation	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1
Ribosome-associated quality control	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
ribosomal small subunit biogenesis	2
ribosome	2
nuclear lumen	2
intracellular membraneless organelle	2
protein-RNA complex assembly	1
ribosome assembly	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
rRNA processing	1
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
nucleic acid binding	1
structural molecule activity	1
mRNA binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
asymmetric synapse	1
postsynaptic specialization	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

322 interactions, top by confidence:

A	B	Type	Score
AK6	RPS14	psi-mi:“MI:0915”(physical association)	0.740
RPS14	AK6	psi-mi:“MI:0915”(physical association)	0.740
RPS14	KRR1	psi-mi:“MI:0915”(physical association)	0.740
PIP4K2A	AHCYL1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RPS3A	RPS14	psi-mi:“MI:0915”(physical association)	0.670
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
PSMD9	RPS14	psi-mi:“MI:0407”(direct interaction)	0.610
PSMD9	RPS14	psi-mi:“MI:0915”(physical association)	0.610
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
NOM1	RPLP0	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
TSR1	PARN	psi-mi:“MI:0914”(association)	0.530
L3HYPDH	CCNE2	psi-mi:“MI:0914”(association)	0.530
DHX57	APOD	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (802): RPS14 (Affinity Capture-MS), RPS14 (Affinity Capture-MS), TAF9 (Two-hybrid), RPS14 (Affinity Capture-MS), RPS14 (Affinity Capture-MS), RPS14 (Affinity Capture-MS), TAF9 (Two-hybrid), RPS14 (Affinity Capture-MS), HNRNPUL2 (Co-fractionation), NDUFS4 (Co-fractionation), RPL10A (Co-fractionation), RPL12 (Co-fractionation), RPL15 (Co-fractionation), RPL17 (Co-fractionation), RPL23A (Co-fractionation)

ESM2 similar proteins: A0LRM6, A0PQC4, A0QIY2, A0RWI9, A1RWT7, A4QEZ2, A7H9F3, A8LC50, A9WPV8, B1VGC2, B2HKS2, B3DQD1, B7GNC3, B8J1Y4, C0HKA0, C0HKA1, C3PH19, C5C9T1, G1T1F0, O22584, P0CT56, P0CT57, P13471, P19115, P19950, P19951, P42036, P46295, P48150, P48855, P62263, P62264, P62265, Q08699, Q0RRR5, Q1DAM6, Q1HR24, Q2N9C8, Q30WJ0, Q3AHW1

Diamond homologs: A0A1D8PDT3, A0B9L3, A0RWI9, A1RRY6, A1RWT7, A2BK78, A2SSV8, A3CWH8, A3DMQ5, A3MX63, A4FWL3, A4WLE0, A4YIN3, A5UN54, A6UPW6, A6UW04, A6VGQ8, A6W369, A7IAH6, A8A8W4, A8IAN8, A8M9Z7, B1L796, B1Y8B3, B2UEJ5, B5XJ61, B6YSQ2, C0HKA0, C0HKA1, C5A250, C6A1B2, G1T1F0, O22584, O26143, O28001, P06367, P0CT56, P0CT57, P10788, P13471

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS14	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 210 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TRAF6 mediated NF-kB activation	6	18.3×	2e-05
Eukaryotic Translation Initiation	7	14.4×	1e-05
Cap-dependent Translation Initiation	7	14.4×	1e-05
SARS-CoV-1 modulates host translation machinery	7	14.4×	1e-05
Formation of the ternary complex, and subsequently, the 43S complex	10	14.4×	9e-08
Nonsense-Mediated Decay (NMD)	9	14.0×	5e-07
Ribosomal scanning and start codon recognition	11	14.0×	2e-08
Eukaryotic Translation Elongation	7	13.0×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	13	16.2×	7e-10
translational initiation	8	15.7×	9e-06
regulation of translational initiation	6	15.3×	3e-04
cytoplasmic translation	15	15.2×	6e-11
canonical NF-kappaB signal transduction	7	14.0×	1e-04
mRNA stabilization	7	14.0×	1e-04
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	12.8×	3e-03
intrinsic apoptotic signaling pathway	6	11.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

846 predictions. Top by Δscore:

Variant	Effect	Δscore
5:150445683:GTCC:G	acceptor_loss	1.0000
5:150445684:TC:T	acceptor_gain	1.0000
5:150445684:TCCT:T	acceptor_loss	1.0000
5:150445685:CC:C	acceptor_gain	1.0000
5:150445686:C:CC	acceptor_gain	1.0000
5:150446796:TCGTA:T	donor_loss	1.0000
5:150446797:CGTAC:C	donor_loss	1.0000
5:150446798:GTACC:G	donor_loss	1.0000
5:150446800:A:AC	donor_gain	1.0000
5:150446801:C:CC	donor_gain	1.0000
5:150446801:C:CG	donor_loss	1.0000
5:150446801:CCT:C	donor_gain	1.0000
5:150446804:ATTT:A	donor_gain	1.0000
5:150446810:T:TA	donor_gain	1.0000
5:150446857:TGC:T	donor_gain	1.0000
5:150446960:TTCC:T	acceptor_gain	1.0000
5:150446961:TCC:T	acceptor_gain	1.0000
5:150446961:TCCC:T	acceptor_loss	1.0000
5:150446962:CC:C	acceptor_gain	1.0000
5:150446962:CCC:C	acceptor_gain	1.0000
5:150446963:CC:C	acceptor_gain	1.0000
5:150446964:C:CC	acceptor_gain	1.0000
5:150446964:CTGG:C	acceptor_loss	1.0000
5:150446965:T:C	acceptor_loss	1.0000
5:150447583:A:AC	donor_gain	1.0000
5:150447584:C:CC	donor_gain	1.0000
5:150447584:CTTG:C	donor_gain	1.0000
5:150447731:CATTT:C	acceptor_gain	1.0000
5:150447732:ATTT:A	acceptor_gain	1.0000
5:150447733:TTT:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000272958 (5:150445806 A>G), RS1000775775 (5:150449969 C>G,T), RS1001394383 (5:150444788 G>C), RS1001542470 (5:150442841 G>C), RS1001708048 (5:150449242 T>C), RS1001976021 (5:150450601 C>T), RS1002117875 (5:150444829 C>A), RS1002410358 (5:150450725 C>T), RS1002823281 (5:150447965 A>G), RS1003409586 (5:150442586 A>G,T), RS1003693221 (5:150445867 G>A), RS1003794151 (5:150446214 C>T), RS1003825126 (5:150446450 C>T), RS1003909369 (5:150450761 G>A,C,T), RS1004018617 (5:150445077 G>A)

Disease associations

OMIM: gene MIM:130620 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0001442	Typified by somatic mosaicism
HP:0001466	Contiguous gene syndrome
HP:0001877	Abnormal erythrocyte morphology
HP:0001882	Decreased total leukocyte count
HP:0001892	Abnormal bleeding
HP:0001894	Thrombocytosis
HP:0001972	Macrocytic anemia
HP:0002863	Myelodysplasia
HP:0003584	Late onset
HP:0003745	Sporadic
HP:0004808	Acute myeloid leukemia
HP:0004861	Refractory macrocytic anemia
HP:0005528	Bone marrow hypocellularity
HP:0010972	Anemia of inadequate production
HP:0011273	Anisocytosis
HP:0011992	Abnormal neutrophil morphology
HP:0012129	Abnormality of bone marrow stromal cells
HP:0012133	Erythroid hypoplasia
HP:0012143	Abnormal megakaryocyte morphology
HP:0012148	Multiple lineage myelodysplasia
HP:0025435	Increased circulating lactate dehydrogenase concentration
HP:0031020	Bone marrow hypercellularity
HP:0031035	Chronic infection
HP:0031385	Megakaryocyte nucleus hypolobulation

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001524_35	Visceral adipose tissue/subcutaneous adipose tissue ratio	8.000000e-06
GCST004131_47	Inflammatory bowel disease	3.000000e-15
GCST004132_24	Crohn’s disease	2.000000e-19

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067568 (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 52 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
6.05	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
5.28	Kd	5299	nM	CHEMBL3752910
5.28	ED50	5299	nM	CHEMBL3752910
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 207 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
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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149286: Binding affinity to human RPS14 incubated for 45 mins by Kinobead based pull down assay	kd	5.2994	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects expression	4
sodium arsenite	increases expression, affects binding, decreases reaction, decreases activity, decreases expression	3
bisphenol F	affects cotreatment, increases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
decabromobiphenyl ether	increases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
nabiximols	increases expression	1
Sunitinib	increases expression	1
Caffeine	increases expression	1
Cisplatin	affects response to substance	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	decreases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Indomethacin	affects cotreatment, increases expression	1

ChEMBL screening assays

90 unique, capped per target: 90 binding

Representative assays (with source publication via chembl_document):

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

Clinical trials (associated diseases)

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