RPL14

Summary

RPL14 (ribosomal protein L14, HGNC:10305) is a protein-coding gene on chromosome 3p22.1, encoding Large ribosomal subunit protein eL14 (P50914). Component of the large ribosomal subunit. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L14E family of ribosomal proteins. It contains a basic region-leucine zipper (bZIP)-like domain. The protein is located in the cytoplasm. This gene contains a trinucleotide (GCT) repeat tract whose length is highly polymorphic; these triplet repeats result in a stretch of alanine residues in the encoded protein. Transcript variants utilizing alternative polyA signals and alternative 5’-terminal exons exist but all encode the same protein. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 9045 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 27 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001034996

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10305
Approved symbol	RPL14
Name	ribosomal protein L14
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	L14, hRL14, RL14, CTG-B33, eL14
Ensembl gene	ENSG00000188846
Ensembl biotype	protein_coding
OMIM	617414
Entrez	9045

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 retained_intron, 3 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000338970, ENST00000396203, ENST00000416518, ENST00000435633, ENST00000461368, ENST00000465280, ENST00000465325, ENST00000479563, ENST00000481798

RefSeq mRNA: 2 — MANE Select: NM_001034996 NM_001034996, NM_003973

CCDS: CCDS33739, CCDS43070

Canonical transcript exons

ENST00000396203 — 6 exons

Exon	Start	End
ENSE00001524220	40457339	40457474
ENSE00003524879	40461608	40461661
ENSE00003526731	40461407	40461506
ENSE00003542826	40458642	40458736
ENSE00003666821	40457890	40457991
ENSE00003694887	40461939	40468587

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 99.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 651.3094 / max 8907.3784, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36180	651.3094	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	99.78	gold quality
body of pancreas	UBERON:0001150	99.76	gold quality
right ovary	UBERON:0002118	99.76	gold quality
ganglionic eminence	UBERON:0004023	99.74	gold quality
endocervix	UBERON:0000458	99.73	gold quality
skin of abdomen	UBERON:0001416	99.73	gold quality
mucosa of stomach	UBERON:0001199	99.72	gold quality
body of uterus	UBERON:0009853	99.72	gold quality
cortical plate	UBERON:0005343	99.71	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.71	gold quality
body of stomach	UBERON:0001161	99.70	gold quality
skin of leg	UBERON:0001511	99.70	gold quality
ectocervix	UBERON:0012249	99.70	gold quality
right lobe of thyroid gland	UBERON:0001119	99.69	gold quality
right uterine tube	UBERON:0001302	99.69	gold quality
right lung	UBERON:0002167	99.69	gold quality
lower esophagus	UBERON:0013473	99.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.69	gold quality
colonic epithelium	UBERON:0000397	99.68	gold quality
left lobe of thyroid gland	UBERON:0001120	99.68	gold quality
popliteal artery	UBERON:0002250	99.68	gold quality
tibial artery	UBERON:0007610	99.68	gold quality
granulocyte	CL:0000094	99.67	gold quality
monocyte	CL:0000576	99.67	gold quality
leukocyte	CL:0000738	99.67	gold quality
left uterine tube	UBERON:0001303	99.67	gold quality
minor salivary gland	UBERON:0001830	99.67	gold quality
adenohypophysis	UBERON:0002196	99.67	gold quality
metanephros cortex	UBERON:0010533	99.67	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	6158.80
E-CURD-122	yes	4576.88
E-MTAB-7249	yes	1115.03
E-CURD-88	yes	65.27
E-MTAB-9221	yes	57.64
E-HCAD-11	yes	44.33
E-MTAB-6678	yes	39.79
E-MTAB-9067	yes	27.02
E-HCAD-9	yes	26.44
E-GEOD-135922	yes	22.74
E-CURD-112	yes	21.60
E-HCAD-35	yes	7.92
E-GEOD-137537	yes	5.64
E-CURD-98	no	5254.36
E-MTAB-7407	no	4657.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting RPL14, 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-33A-3P	99.70	70.27	3362
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-3920	97.75	69.02	1168

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 1)

• Human/eukaryotic ribosomal protein L14 (RPL14/eL14) overexpression represses proliferation, migration, invasion and EMT process in nasopharyngeal carcinoma. (PMID:34057029)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl14	ENSDARG00000103433
mus_musculus	Rpl14	ENSMUSG00000025794
rattus_norvegicus	Rpl14	ENSRNOG00000019007
rattus_norvegicus	Rpl14l1	ENSRNOG00000031061
rattus_norvegicus	Rpl14l2	ENSRNOG00000032160
drosophila_melanogaster	RpL14	FBGN0017579
caenorhabditis_elegans	rpl-14	WBGENE00004426

Protein

Protein identifiers

Large ribosomal subunit protein eL14 — P50914 (reviewed: P50914)

Alternative names: 60S ribosomal protein L14, CAG-ISL 7

All UniProt accessions (3): E7EPB3, F8WDZ7, P50914

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Component of the large ribosomal subunit.

Subcellular location. Cytoplasm.

Polymorphism. The poly-Ala stretch is highly polymorphic.

Similarity. Belongs to the eukaryotic ribosomal protein eL14 family.

RefSeq proteins (2): NP_001030168, NP_003964 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002784	Ribosomal_eL14_dom	Domain
IPR008991	Translation_prot_SH3-like_sf	Homologous_superfamily
IPR014722	Rib_uL2_dom2	Homologous_superfamily
IPR039660	Ribosomal_eL14	Family

Pfam: PF01929

UniProt features (26 total): sequence variant 8, repeat 6, modified residue 5, region of interest 3, initiator methionine 1, chain 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

193 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
8K2C	ELECTRON MICROSCOPY	2.4
8XSX	ELECTRON MICROSCOPY	2.4
9SPF	ELECTRON MICROSCOPY	2.4
9SPI	ELECTRON MICROSCOPY	2.4
8JDL	ELECTRON MICROSCOPY	2.42
9S3C	ELECTRON MICROSCOPY	2.42
8FKV	ELECTRON MICROSCOPY	2.47
9QLO	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48
9P8B	ELECTRON MICROSCOPY	2.48
7XNY	ELECTRON MICROSCOPY	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50914-F1	79.20	0.67

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): 79, 85, 85, 139, 204, 124

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: 259 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, TGCGCANK_UNKNOWN, SWEET_KRAS_ONCOGENIC_SIGNATURE, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCM_NPM1, MORF_UBE2I, MORF_HDAC1, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, SHIPP_DLBCL_CURED_VS_FATAL_DN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION

GO Biological Process (4): cytoplasmic translation (GO:0002181), rRNA processing (GO:0006364), translation (GO:0006412), ribosomal large subunit biogenesis (GO:0042273)

GO Molecular Function (4): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (10): cytoplasm (GO:0005737), cytosol (GO:0005829), postsynaptic density (GO:0014069), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), extracellular exosome (GO:0070062), ribosome (GO:0005840), large ribosomal subunit (GO:0015934), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Ribosome-associated quality control	3
Translation	2
Cap-dependent Translation Initiation	2
Nonsense-Mediated Decay (NMD)	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	1
rRNA processing in the nucleus and cytosol	1
Signaling by ROBO receptors	1
Cellular response to starvation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
ribosome biogenesis	2
ribosome	2
translation	1
RNA processing	1
rRNA metabolic process	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
ribonucleoprotein complex biogenesis	1
nucleic acid binding	1
structural molecule activity	1
cell adhesion molecule binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
asymmetric synapse	1
postsynaptic specialization	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
extracellular vesicle	1
intracellular membraneless organelle	1
ribosomal subunit	1
protein-containing complex	1

Protein interactions and networks

STRING

3240 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL14	RPS8	P09058	924
RPL14	RPS3	P23396	875
RPL14	RPS24	P16632	866
RPL14	RPL36	Q9Y3U8	851
RPL14	RPL6	Q02878	843
RPL14	RPL5	P46777	799
RPL14	RPS19	P39019	795
RPL14	RPL29	P47914	784
RPL14	RPL9	P32969	784
RPL14	RPL12	P30050	781
RPL14	RPL3	P39023	779
RPL14	RPS11	P04643	776
RPL14	RPL11	P25121	775
RPL14	RPS26	P02383	773
RPL14	RPL21	P46778	769

IntAct

247 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
STAU1	RPLP0	psi-mi:“MI:0914”(association)	0.750
RPL4	RPL14	psi-mi:“MI:0915”(physical association)	0.740
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPL14	H1-4	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
CHLSN	RPL14	psi-mi:“MI:0914”(association)	0.530
RPL13	RPLP1	psi-mi:“MI:0914”(association)	0.530
DDX31	MAGEB2	psi-mi:“MI:0914”(association)	0.530
RRP8	MAGEB2	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (992): RPL14 (Affinity Capture-MS), RPL14 (Two-hybrid), RPL14 (Affinity Capture-MS), RPL14 (Affinity Capture-MS), RPL14 (Affinity Capture-MS), RPL14 (Affinity Capture-MS), RPL14 (Affinity Capture-MS), RPL14 (Affinity Capture-MS), RPL14 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), SRRM1 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), PRPF4B (Affinity Capture-MS), VPRBP (Affinity Capture-MS)

ESM2 similar proteins: A1XQU3, A1XQU5, G1SE28, G1SKF7, G1SZ12, G1TXF6, O65743, O94776, P21533, P37108, P38666, P47911, P50888, P50914, P55844, P61122, P61353, P61354, P61355, P61356, P61357, P61358, P83731, P83732, Q02878, Q2YGT9, Q3T0U2, Q42347, Q4R5C7, Q4R8Z4, Q58DQ3, Q63507, Q66WF5, Q6QMZ4, Q6Y263, Q862I1, Q8BP67, Q8ISQ3, Q8JGR4, Q90YQ0

Diamond homologs: A0A1D8PFL9, A1XQU3, G1SZ12, O46160, O94238, P36105, P38754, P50914, P55841, P55844, Q24C27, Q3T0U2, Q54Z09, Q63507, Q7XYA7, Q95ZE8, Q9CR57, Q9SIM4, Q9T043, A1RTL6, A3DND4, A3MS76, A4WH36, B1YA63, B6YSP2, B8D5U3, C6A188, P54054, P55842, Q4JAJ9, Q8TX43, Q8U2L5, Q975L7, Q9YDD7, A1RXE1, A2BME7, A4FYK2, A4YCT0, A6USC0, A6VJT0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL14	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 212 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
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	25	20.0×	4e-24
Peptide chain elongation	23	19.9×	3e-22
Viral mRNA Translation	23	19.9×	3e-22
Formation of a pool of free 40S subunits	26	19.8×	7e-25
SRP-dependent cotranslational protein targeting to membrane	29	19.8×	2e-27
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	23	19.6×	4e-22
Eukaryotic Translation Termination	24	19.6×	6e-23
L13a-mediated translational silencing of Ceruloplasmin expression	28	19.2×	3e-26

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	26	25.1×	1e-26
positive regulation of transcription by RNA polymerase III	5	24.4×	2e-04
ribosome biogenesis	5	16.2×	1e-03
translational initiation	8	14.9×	2e-05
translation	27	14.4×	5e-21
ribosomal large subunit biogenesis	6	13.9×	6e-04
mRNA stabilization	7	13.4×	2e-04
rRNA processing	15	11.1×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

625 predictions. Top by Δscore:

Variant	Effect	Δscore
3:40457882:A:AG	acceptor_gain	1.0000
3:40457883:A:G	acceptor_gain	1.0000
3:40457885:TTTA:T	acceptor_loss	1.0000
3:40457888:A:AG	acceptor_gain	1.0000
3:40457888:AG:A	acceptor_gain	1.0000
3:40457889:G:GA	acceptor_loss	1.0000
3:40457889:G:GG	acceptor_gain	1.0000
3:40457889:GG:G	acceptor_gain	1.0000
3:40457889:GGT:G	acceptor_gain	1.0000
3:40457987:ACAGG:A	donor_gain	1.0000
3:40457988:CAGG:C	donor_gain	1.0000
3:40457989:AGG:A	donor_gain	1.0000
3:40457990:GG:G	donor_gain	1.0000
3:40457990:GGG:G	donor_gain	1.0000
3:40457990:GGGTA:G	donor_loss	1.0000
3:40457991:GG:G	donor_gain	1.0000
3:40457991:GGTA:G	donor_loss	1.0000
3:40457992:G:GG	donor_gain	1.0000
3:40457992:GTAA:G	donor_loss	1.0000
3:40458634:T:TA	acceptor_gain	1.0000
3:40458637:TCTAG:T	acceptor_loss	1.0000
3:40458638:CTAGG:C	acceptor_loss	1.0000
3:40458639:TAGGC:T	acceptor_loss	1.0000
3:40458640:A:AG	acceptor_gain	1.0000
3:40458640:A:T	acceptor_loss	1.0000
3:40458640:AG:A	acceptor_gain	1.0000
3:40458641:G:GT	acceptor_gain	1.0000
3:40458641:GG:G	acceptor_gain	1.0000
3:40458641:GGC:G	acceptor_gain	1.0000
3:40458641:GGCT:G	acceptor_gain	1.0000

AlphaMissense

1411 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:40457893:T:C	F3L	0.999
3:40457895:C:A	F3L	0.999
3:40457895:C:G	F3L	0.999
3:40461462:T:A	W86R	0.999
3:40461462:T:C	W86R	0.999
3:40461464:G:C	W86C	0.999
3:40461464:G:T	W86C	0.999
3:40461477:T:A	W91R	0.999
3:40461477:T:C	W91R	0.999
3:40457914:G:C	G10R	0.998
3:40457915:G:A	G10D	0.998
3:40457924:C:A	A13D	0.998
3:40457939:G:A	G18E	0.998
3:40457960:T:A	V25D	0.998
3:40457966:T:A	I27N	0.998
3:40457975:T:A	V30D	0.998
3:40458643:C:A	A36D	0.998
3:40458649:T:A	V38D	0.998
3:40458655:G:A	G40E	0.998
3:40458676:G:C	R47T	0.998
3:40461479:G:C	W91C	0.998
3:40461479:G:T	W91C	0.998
3:40461635:T:C	F110L	0.998
3:40461637:T:A	F110L	0.998
3:40461637:T:G	F110L	0.998
3:40457915:G:T	G10V	0.997
3:40457930:T:A	V15D	0.997
3:40457935:T:C	F17L	0.997
3:40457937:T:A	F17L	0.997
3:40457937:T:G	F17L	0.997

dbSNP variants (sampled 300 via entrez): RS1000280579 (3:40466324 T>C), RS1000371085 (3:40463571 T>C), RS1000744247 (3:40455376 G>T), RS1000847876 (3:40468460 C>G,T), RS1001007226 (3:40465081 CAAG>C), RS1001892189 (3:40467085 T>C), RS1002162982 (3:40457517 C>T), RS1002236411 (3:40457401 A>C,G,T), RS1002237483 (3:40462873 G>A), RS1002314769 (3:40462526 G>A), RS1002335789 (3:40467986 A>C,G), RS1002466381 (3:40467366 A>G), RS1002564514 (3:40464600 G>C), RS1002706607 (3:40457411 A>ACCT), RS1002795412 (3:40462373 C>T)

Disease associations

OMIM: gene MIM:617414 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005232_29	Neuroticism	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066877 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds).

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

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

ChEMBL bioactivities

50 potent at pChembl≥5 of 54 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.73	Kd	186.6	nM	CHEMBL3752910
6.73	ED50	186.6	nM	CHEMBL3752910
6.52	IC50	300	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4574496
6.41	IC50	390	nM	CHEMBL4126894
6.39	IC50	410	nM	CHEMBL4114159
6.35	IC50	450	nM	CHEMBL4126496
6.30	IC50	500	nM	CHEMBL4574496
6.30	IC50	500	nM	CHEMBL4560206
6.16	IC50	690	nM	CHEMBL4130157
6.15	IC50	710	nM	CHEMBL4108338
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	IC50	900	nM	CHEMBL4126894
6.05	IC50	900	nM	CHEMBL4126496
6.04	IC50	920	nM	CHEMBL4554909
5.97	IC50	1060	nM	CHEMBL4128388
5.89	IC50	1290	nM	CHEMBL4130157
5.86	IC50	1370	nM	CHEMBL4107559
5.84	IC50	1440	nM	CHEMBL4108338
5.81	IC50	1540	nM	CHEMBL4534859
5.76	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
5.14	Kd	7315	nM	CHEMBL5653589
5.14	ED50	7315	nM	CHEMBL5653589
5.13	IC50	7400	nM	CHLORAMPHENICOL SULFATE SALT
5.09	IC50	8040	nM	CHEMBL4128250
5.08	IC50	8370	nM	CHEMBL4128250
5.03	IC50	9320	nM	CHEMBL4127016
5.03	IC50	9240	nM	CHEMBL4128560

PubChem BioAssay actives

48 with measured affinity, of 209 total; 28 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149245: Binding affinity to human RPL14 incubated for 45 mins by Kinobead based pull down assay	kd	0.1866	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1585498: Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method	ic50	0.3000	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-3-[4-(triazolo[4,5-b]pyridin-3-yl)phenyl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3800	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3900	uM
N-(3-chloro-2-pyridinyl)-4-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4100	uM
N-(3-chloro-2-pyridinyl)-4-(5-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4500	uM
N-(1-methylpyrrolo[2,3-c]pyridin-7-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.5000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.6900	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-5-(triazolo[4,5-b]pyridin-3-yl)pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.7100	uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylpiperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.9200	uM
N-isoquinolin-1-yl-4-(1-methylpyrazol-4-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	1.0600	uM
N-isoquinolin-1-yl-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	1.5400	uM
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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149245: Binding affinity to human RPL14 incubated for 45 mins by Kinobead based pull down assay	kd	7.3150	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	4
Particulate Matter	decreases expression, increases abundance, increases expression	3
chloropicrin	affects expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Smoke	decreases expression, increases abundance	2
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
N-benzyloxycarbonylprolylprolinal	increases expression	1
artenimol	affects binding	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
epigallocatechin gallate	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1

ChEMBL screening assays

90 unique, capped per target: 90 binding

Representative assays (with source publication via chembl_document):

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

Clinical trials (associated diseases)

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