RPL4

Summary

RPL4 (ribosomal protein L4, HGNC:10353) is a protein-coding gene on chromosome 15q22.31, encoding Large ribosomal subunit protein uL4 (P36578). 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 L4E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6124 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 68 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_000968

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10353
Approved symbol	RPL4
Name	ribosomal protein L4
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	L4, uL4
Ensembl gene	ENSG00000174444
Ensembl biotype	protein_coding
OMIM	180479
Entrez	6124

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 18 protein_coding, 10 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000307961, ENST00000561554, ENST00000561775, ENST00000563473, ENST00000564439, ENST00000564517, ENST00000564647, ENST00000564744, ENST00000565723, ENST00000566039, ENST00000566491, ENST00000566622, ENST00000566624, ENST00000567229, ENST00000568588, ENST00000569438, ENST00000569696, ENST00000856033, ENST00000856034, ENST00000912452, ENST00000912453, ENST00000912454, ENST00000912455, ENST00000912456, ENST00000912457, ENST00000912458, ENST00000912459, ENST00000912460, ENST00000912461, ENST00000941454, ENST00000941455

RefSeq mRNA: 1 — MANE Select: NM_000968 NM_000968

CCDS: CCDS10218

Canonical transcript exons

ENST00000307961 — 10 exons

Exon	Start	End
ENSE00001199254	66498015	66499652
ENSE00001920037	66504788	66504855
ENSE00003461599	66501375	66501504
ENSE00003485616	66500949	66501105
ENSE00003514697	66500293	66500376
ENSE00003629700	66503358	66503529
ENSE00003642946	66500056	66500176
ENSE00003662192	66501788	66501912
ENSE00003688735	66503058	66503164
ENSE00003755397	66502612	66502750

Expression profiles

Bgee: expression breadth ubiquitous, 309 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.2339 / max 550.8642, expressed in 1811 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150600	49.1203	1811
150596	1.9084	1115
150599	0.7836	491
150597	0.4006	190
150602	0.0105	4
150603	0.0105	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.99	gold quality
embryo	UBERON:0000922	99.96	gold quality
ganglionic eminence	UBERON:0004023	99.96	gold quality
cartilage tissue	UBERON:0002418	99.95	gold quality
ventricular zone	UBERON:0003053	99.95	gold quality
mammalian vulva	UBERON:0000997	99.94	gold quality
cauda epididymis	UBERON:0004360	99.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.92	gold quality
stromal cell of endometrium	CL:0002255	99.92	gold quality
smooth muscle tissue	UBERON:0001135	99.92	gold quality
superficial temporal artery	UBERON:0001614	99.92	gold quality
gluteal muscle	UBERON:0002000	99.92	gold quality
caput epididymis	UBERON:0004358	99.92	gold quality
urinary bladder	UBERON:0001255	99.91	gold quality
left ovary	UBERON:0002119	99.91	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.91	gold quality
islet of Langerhans	UBERON:0000006	99.90	gold quality
pituitary gland	UBERON:0000007	99.90	gold quality
zone of skin	UBERON:0000014	99.90	gold quality
endocervix	UBERON:0000458	99.90	gold quality
ovary	UBERON:0000992	99.90	gold quality
skin of abdomen	UBERON:0001416	99.90	gold quality
skin of leg	UBERON:0001511	99.90	gold quality
epithelium of nasopharynx	UBERON:0001951	99.90	gold quality
right ovary	UBERON:0002118	99.90	gold quality
adenohypophysis	UBERON:0002196	99.90	gold quality
upper arm skin	UBERON:0004263	99.90	gold quality
corpus epididymis	UBERON:0004359	99.90	gold quality
tongue squamous epithelium	UBERON:0006919	99.90	gold quality
adult organism	UBERON:0007023	99.90	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	4329.01
E-MTAB-9543	yes	3551.85
E-CURD-122	yes	85.33
E-CURD-88	yes	57.30
E-HCAD-11	yes	49.65
E-MTAB-9221	yes	49.27
E-GEOD-125970	yes	45.27
E-CURD-46	yes	42.29
E-MTAB-8410	yes	40.90
E-HCAD-13	yes	25.60
E-HCAD-9	yes	25.58
E-GEOD-135922	yes	19.50
E-MTAB-10042	yes	14.00
E-MTAB-9801	yes	5.99
E-GEOD-137537	yes	5.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYB

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 5)

• Results show that RPL4, RPLP0, and HSPCB were the most stable reference genes in ovarian tissues. (PMID:20705598)
• Mouse and human RPL4 enhance MoMLV gag-pol readthrough. (PMID:22718819)
• insights into the mechanisms by which EBV uses nucleolin and RPL4 to establish persistent B-lymphoblastoid cell infection (PMID:26858444)
• SNHG7 contributed to hepatocellular carcinoma progression by regulating miR-122-5p and RPL4. (PMID:31545291)
• The interaction between nucleophosmin/NPM1 and the large ribosomal subunit precursors contribute to maintaining the nucleolar structure. (PMID:33039556)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl4	ENSDARG00000041182
mus_musculus	Rpl4	ENSMUSG00000032399
rattus_norvegicus	Rpl4-ps1	ENSRNOG00000009614
drosophila_melanogaster	RpL4	FBGN0003279
caenorhabditis_elegans	rpl-4	WBGENE00004415

Protein

Protein identifiers

Large ribosomal subunit protein uL4 — P36578 (reviewed: P36578)

Alternative names: 60S ribosomal protein L1, 60S ribosomal protein L4

All UniProt accessions (4): P36578, H3BM89, H3BTP7, H3BU31

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. May bind IPO9 with low affinity. Interacts with RBM3.

Subcellular location. Cytoplasm.

Post-translational modifications. Citrullinated by PADI4.

Similarity. Belongs to the universal ribosomal protein uL4 family.

RefSeq proteins (1): NP_000959* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002136	Ribosomal_uL4	Family
IPR013000	Ribosomal_uL4_euk_arc_CS	Conserved_site
IPR023574	Ribosomal_uL4_dom_sf	Homologous_superfamily
IPR025755	Ribos_uL4_C_dom	Domain
IPR045240	Ribosomal_uL4_euk_arc	Family

Pfam: PF00573, PF14374

UniProt features (26 total): modified residue 13, sequence conflict 5, cross-link 3, compositionally biased region 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

199 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8A3D	ELECTRON MICROSCOPY	1.67
8GLP	ELECTRON MICROSCOPY	1.67
8QYX	ELECTRON MICROSCOPY	1.78
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8QFD	ELECTRON MICROSCOPY	2.2
8YOP	ELECTRON MICROSCOPY	2.2
9GUL	ELECTRON MICROSCOPY	2.2
9O3V	ELECTRON MICROSCOPY	2.2
9O3Y	ELECTRON MICROSCOPY	2.2
8JDK	ELECTRON MICROSCOPY	2.26
8G5Y	ELECTRON MICROSCOPY	2.29
9S3D	ELECTRON MICROSCOPY	2.32
9RPV	ELECTRON MICROSCOPY	2.35
9S3B	ELECTRON MICROSCOPY	2.38
7OW7	ELECTRON MICROSCOPY	2.4
8K2C	ELECTRON MICROSCOPY	2.4
8XSX	ELECTRON MICROSCOPY	2.4
9SPF	ELECTRON MICROSCOPY	2.4
9SPI	ELECTRON MICROSCOPY	2.4
8JDL	ELECTRON MICROSCOPY	2.42
9S3C	ELECTRON MICROSCOPY	2.42
8FKV	ELECTRON MICROSCOPY	2.47
9QLO	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48
9P8B	ELECTRON MICROSCOPY	2.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36578-F1	87.89	0.84

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 (16): 266, 290, 295, 300, 333, 353, 364, 365, 239, 327, 364, 2, 14, 97, 106, 259

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: 272 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, MODULE_151, GCANCTGNY_MYOD_Q6, CMYB_01, GCM_NPM1, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, GGCNKCCATNK_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_MUSCLE_CONTRACTION

GO Biological Process (3): cytoplasmic translation (GO:0002181), translation (GO:0006412), RNA processing (GO:0006396)

GO Molecular Function (3): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (14): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), rough endoplasmic reticulum (GO:0005791), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), nuclear body (GO:0016604), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), extracellular exosome (GO:0070062), ribonucleoprotein complex (GO:1990904), ribosome (GO:0005840)

Reactome top-level categories

Rollup of top-11 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	3
cellular anatomical structure	3
ribosome	2
intracellular membrane-bounded organelle	2
cytoplasm	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
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
nucleic acid binding	1
structural molecule activity	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
endoplasmic reticulum	1
cell-substrate junction	1
nucleoplasm	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
extracellular vesicle	1
protein-containing complex	1

Protein interactions and networks

STRING

5907 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL4	RPLP0	P05388	869
RPL4	RPL3	P39023	852
RPL4	RPL6	Q02878	841
RPL4	RPL22	P35268	838
RPL4	RPL5	P46777	824
RPL4	RPS3	P23396	822
RPL4	RPL11	P25121	814
RPL4	SBDS	Q9Y3A5	809
RPL4	RPL12	P30050	808
RPL4	RPL9	P32969	797
RPL4	RPL8	P25120	786
RPL4	RPL7	P18124	781
RPL4	EFL1	Q7Z2Z2	772
RPL4	RPL19	P14118	771
RPL4	RPL28	P46779	768

IntAct

449 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
RPL4	RPL14	psi-mi:“MI:0915”(physical association)	0.740
RPS6	RPL4	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RPL4	HTT	psi-mi:“MI:0915”(physical association)	0.680
RPL4	RPL18	psi-mi:“MI:0915”(physical association)	0.670
RPL4	RPL18A	psi-mi:“MI:0915”(physical association)	0.670
RPL28	RPL4	psi-mi:“MI:0915”(physical association)	0.670
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
RPL4	RPS20	psi-mi:“MI:0915”(physical association)	0.620
RPL4	RPS20	psi-mi:“MI:0914”(association)	0.620

BioGRID (1294): RPL4 (Affinity Capture-MS), RPL4 (Two-hybrid), RPL4 (Affinity Capture-MS), RPL4 (Affinity Capture-MS), RPL4 (Affinity Capture-MS), RPL4 (Affinity Capture-MS), RPL4 (Affinity Capture-MS), RPL4 (Reconstituted Complex), RPL4 (Affinity Capture-MS), RPL4 (Affinity Capture-MS), RPL4 (Affinity Capture-MS), EIF6 (Co-fractionation), FTSJ3 (Co-fractionation), GTPBP4 (Co-fractionation), NIP7 (Co-fractionation)

ESM2 similar proteins: A0A1D8PFV1, A0A1D8PK43, A2BTD0, A3PF40, A8G754, A9BCP0, G1SVW5, O02056, O15594, O42848, O42991, O43004, P02385, P08429, P09180, P0DJ15, P0DJ55, P10664, P26784, P26785, P35679, P36578, P49165, P49626, P49669, P49691, P50878, P93099, Q10192, Q28346, Q318J1, Q3AMN7, Q3AUW9, Q4DZP2, Q4N438, Q4QG98, Q4R5P9, Q54Z69, Q553M7, Q58DW0

Diamond homologs: A0A1D8PFV1, A0B9W9, A3CSZ8, A4FVY1, A5UL88, A6UQJ1, A6UV67, A6VHD3, A7I5P0, A9A9B7, B0R657, B6YSL4, B9LSS6, C3MQ60, C3MVH9, C3N5S8, C3NEE4, C3NHA8, C4KHF7, C5A285, C6A160, G1SVW5, O02056, O15594, O26111, O28355, O59420, P02385, P08429, P09180, P0DJ55, P10664, P12735, P14117, P35679, P36578, P49165, P49626, P49669, P49691

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL4	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 211 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
Peptide chain elongation	19	18.4×	6e-17
Viral mRNA Translation	19	18.4×	6e-17
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	19	18.2×	6e-17
Selenocysteine synthesis	19	17.4×	9e-17
Eukaryotic Translation Termination	19	17.4×	9e-17
Formation of a pool of free 40S subunits	20	17.1×	6e-17
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	19	17.1×	9e-17
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	19	17.1×	9e-17

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	21	22.1×	1e-19
ribosome biogenesis	5	17.7×	9e-04
ribosomal large subunit biogenesis	7	17.6×	3e-05
intrinsic apoptotic signaling pathway	7	14.3×	1e-04
mRNA stabilization	6	12.5×	9e-04
translation	21	12.3×	2e-14
mitophagy	6	10.8×	2e-03
rRNA processing	13	10.5×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2565 predictions. Top by Δscore:

Variant	Effect	Δscore
15:66499648:TTGTG:T	acceptor_gain	1.0000
15:66499649:TGTG:T	acceptor_gain	1.0000
15:66499650:GTG:G	acceptor_gain	1.0000
15:66499651:TG:T	acceptor_gain	1.0000
15:66499653:C:CC	acceptor_gain	1.0000
15:66499653:CTGC:C	acceptor_loss	1.0000
15:66499657:A:T	acceptor_gain	1.0000
15:66499659:C:CT	acceptor_gain	1.0000
15:66499660:A:T	acceptor_gain	1.0000
15:66499663:T:C	acceptor_gain	1.0000
15:66499663:T:TC	acceptor_gain	1.0000
15:66500052:TCA:T	donor_loss	1.0000
15:66500053:CA:C	donor_loss	1.0000
15:66500054:A:AC	donor_gain	1.0000
15:66500054:ACA:A	donor_loss	1.0000
15:66500054:ACATT:A	donor_gain	1.0000
15:66500055:C:CA	donor_gain	1.0000
15:66500055:C:G	donor_loss	1.0000
15:66500055:CA:C	donor_gain	1.0000
15:66500055:CAT:C	donor_gain	1.0000
15:66500055:CATT:C	donor_gain	1.0000
15:66500055:CATTC:C	donor_gain	1.0000
15:66500058:T:TA	donor_gain	1.0000
15:66500173:CTTG:C	acceptor_gain	1.0000
15:66500174:TTG:T	acceptor_gain	1.0000
15:66500175:TG:T	acceptor_gain	1.0000
15:66500177:C:CC	acceptor_gain	1.0000
15:66500179:A:AC	acceptor_gain	1.0000
15:66500179:A:C	acceptor_gain	1.0000
15:66500288:TTTAC:T	donor_loss	1.0000

AlphaMissense

2767 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:66500107:G:C	N329K	1.000
15:66500107:G:T	N329K	1.000
15:66500111:A:G	L328P	1.000
15:66501015:G:T	A256D	1.000
15:66501024:G:A	T253I	1.000
15:66501028:A:G	W252R	1.000
15:66501028:A:T	W252R	1.000
15:66501030:A:T	I251N	1.000
15:66501040:G:T	R248S	1.000
15:66501042:C:A	G247V	1.000
15:66501042:C:T	G247E	1.000
15:66501043:C:G	G247R	1.000
15:66501043:C:T	G247R	1.000
15:66501051:C:A	G244V	1.000
15:66501051:C:T	G244E	1.000
15:66501052:C:A	G244W	1.000
15:66501052:C:G	G244R	1.000
15:66501052:C:T	G244R	1.000
15:66501054:C:A	G243V	1.000
15:66501054:C:T	G243D	1.000
15:66501055:C:G	G243R	1.000
15:66501060:G:T	A241D	1.000
15:66501105:C:A	G226V	1.000
15:66501105:C:T	G226E	1.000
15:66501375:C:G	G226R	1.000
15:66501375:C:T	G226R	1.000
15:66501382:G:C	N223K	1.000
15:66501382:G:T	N223K	1.000
15:66501386:C:A	R222I	1.000
15:66501392:G:T	A220D	1.000

dbSNP variants (sampled 300 via entrez): RS1000114741 (15:66498688 C>G,T), RS1000194503 (15:66500899 T>C), RS1000289102 (15:66505351 C>A,G,T), RS1000408247 (15:66503846 A>C), RS1000482133 (15:66505594 G>A,T), RS1000707260 (15:66501605 T>G), RS1000796328 (15:66502173 A>T), RS1001559001 (15:66506802 C>T), RS1001567249 (15:66497872 T>C,G), RS1001671524 (15:66498952 G>C), RS1002000334 (15:66498027 A>C), RS1002207676 (15:66498755 G>A,C,T), RS1002237721 (15:66498314 G>C,T), RS1004121045 (15:66498054 C>A), RS1004128618 (15:66497968 G>C,T)

Disease associations

OMIM: gene MIM:180479 | disease phenotypes: MIM:258040

GenCC curated gene-disease

Mondo (1): exstrophy-epispadias complex (MONDO:0017919)

Orphanet (2): Exstrophy-epispadias complex (Orphanet:322), Cloacal exstrophy (Orphanet:93929)

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), CHEMBL6066910 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

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

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

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

ChEMBL bioactivities

48 potent at pChembl≥5 of 54 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.52	IC50	300	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4574496
6.41	IC50	390	nM	CHEMBL4126894
6.39	IC50	410	nM	CHEMBL4114159
6.35	IC50	450	nM	CHEMBL4126496
6.30	IC50	500	nM	CHEMBL4574496
6.30	IC50	500	nM	CHEMBL4560206
6.16	IC50	690	nM	CHEMBL4130157
6.15	IC50	710	nM	CHEMBL4108338
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	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
5.33	Kd	4729	nM	CHEMBL3752910
5.33	ED50	4729	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 209 total; 27 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1585498: Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method	ic50	0.3000	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-3-[4-(triazolo[4,5-b]pyridin-3-yl)phenyl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3800	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3900	uM
N-(3-chloro-2-pyridinyl)-4-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4100	uM
N-(3-chloro-2-pyridinyl)-4-(5-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4500	uM
N-(1-methylpyrrolo[2,3-c]pyridin-7-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.5000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.6900	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-5-(triazolo[4,5-b]pyridin-3-yl)pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.7100	uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
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	2149270: Binding affinity to human RPL4 incubated for 45 mins by Kinobead based pull down assay	kd	4.7286	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
sodium arsenite	decreases expression	2
bisphenol S	affects cotreatment, decreases methylation, increases expression	2
Caffeine	decreases phosphorylation, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	increases expression	1
artenimol	affects binding	1
epigallocatechin gallate	increases expression	1
azoxystrobin	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
deguelin	increases expression	1
corosolic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	decreases expression, affects cotreatment	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)

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

Trial	Phase	Status	Title
NCT04760028	PHASE4	COMPLETED	Study on the Influencing Factors of Electroencephalogram Parameters Under Anesthesia
NCT06106425	Not specified	UNKNOWN	Diagnostic and Prognostic Criteria of EEG in Neonatal Convulsions at Assiut University Children Hospital