RPS4X

Summary

RPS4X (ribosomal protein S4 X-linked, HGNC:10424) is a protein-coding gene on chromosome Xq13.1, encoding Small ribosomal subunit protein eS4, X isoform (P62701). Component of the small ribosomal subunit. It is a common-essential gene (DepMap: required in 97.9% of cancer cell lines).

Cytoplasmic ribosomes, 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 ribosomal protein S4, a component of the 40S subunit. Ribosomal protein S4 is the only ribosomal protein known to be encoded by more than one gene, namely this gene and ribosomal protein S4, Y-linked (RPS4Y). The 2 isoforms encoded by these genes are not identical, but are functionally equivalent. Ribosomal protein S4 belongs to the S4E family of ribosomal proteins. This gene is not subject to X-inactivation. It has been suggested that haploinsufficiency of the ribosomal protein S4 genes plays a role in Turner syndrome; however, this hypothesis is controversial. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6191 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 41 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_001007

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10424
Approved symbol	RPS4X
Name	ribosomal protein S4 X-linked
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Aliases	DXS306, CCG2, SCAR, SCR10, FLJ40595, RPS4, eS4
Ensembl gene	ENSG00000198034
Ensembl biotype	protein_coding
OMIM	312760
Entrez	6191

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 22 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000316084, ENST00000373626, ENST00000470671, ENST00000486733, ENST00000492695, ENST00000897475, ENST00000897476, ENST00000897477, ENST00000919631, ENST00000919632, ENST00000919633, ENST00000919634, ENST00000919635, ENST00000919636, ENST00000919637, ENST00000919638, ENST00000919639, ENST00000919640, ENST00000919641, ENST00000919642, ENST00000919643, ENST00000919644, ENST00000919645, ENST00000944634, ENST00000944635, ENST00000944636

RefSeq mRNA: 1 — MANE Select: NM_001007 NM_001007

CCDS: CCDS14418

Canonical transcript exons

ENST00000316084 — 7 exons

Exon	Start	End
ENSE00000672633	72273801	72273972
ENSE00000672636	72275053	72275150
ENSE00001550090	72277193	72277248
ENSE00001650054	72276157	72276234
ENSE00001945668	72272042	72272772
ENSE00003537305	72273232	72273389
ENSE00003560418	72275544	72275724

Expression profiles

Bgee: expression breadth ubiquitous, 308 present calls, max score 100.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 155.7630 / max 2055.7294, expressed in 1820 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199584	146.9367	1817
199583	4.9873	1529
199585	1.4788	699
199580	0.6297	316
199578	0.5600	314
199581	0.4585	218
199579	0.3659	152
199582	0.3461	135

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	100.00	gold quality
mammary duct	UBERON:0001765	99.99	gold quality
epithelium of mammary gland	UBERON:0003244	99.99	gold quality
pleura	UBERON:0000977	99.98	gold quality
tibia	UBERON:0000979	99.98	gold quality
parietal pleura	UBERON:0002400	99.98	gold quality
visceral pleura	UBERON:0002401	99.98	gold quality
mammalian vulva	UBERON:0000997	99.97	gold quality
superficial temporal artery	UBERON:0001614	99.97	gold quality
epithelium of nasopharynx	UBERON:0001951	99.97	gold quality
corpus epididymis	UBERON:0004359	99.97	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.97	gold quality
nasopharynx	UBERON:0001728	99.96	gold quality
hair follicle	UBERON:0002073	99.96	gold quality
caput epididymis	UBERON:0004358	99.96	gold quality
adult organism	UBERON:0007023	99.96	gold quality
seminal vesicle	UBERON:0000998	99.95	gold quality
epididymis	UBERON:0001301	99.95	gold quality
nipple	UBERON:0002030	99.95	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.95	gold quality
esophagus squamous epithelium	UBERON:0006920	99.95	gold quality
tendon of biceps brachii	UBERON:0008188	99.95	gold quality
lower lobe of lung	UBERON:0008949	99.95	gold quality
skin of hip	UBERON:0001554	99.94	gold quality
cartilage tissue	UBERON:0002418	99.94	gold quality
cauda epididymis	UBERON:0004360	99.94	gold quality
pylorus	UBERON:0001166	99.93	gold quality
palpebral conjunctiva	UBERON:0001812	99.93	gold quality
mammary gland	UBERON:0001911	99.93	gold quality
epithelium of esophagus	UBERON:0001976	99.93	gold quality

Single-cell (SCXA)

Detected in 57 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	6120.46
E-MTAB-9801	yes	4664.80
E-CURD-122	yes	97.85
E-CURD-88	yes	64.23
E-MTAB-9221	yes	56.57
E-MTAB-6678	yes	47.99
E-HCAD-9	yes	27.70
E-CURD-112	yes	22.32
E-MTAB-9543	yes	11.14
E-HCAD-35	yes	8.40
E-GEOD-137537	yes	6.24
E-MTAB-8884	no	15618.43
E-MTAB-7407	no	12198.49
E-HCAD-4	no	11635.43
E-HCAD-1	no	11037.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• levels of RPS4X could be a good indicator for resistance to platinum-based therapy and a prognostic marker for ovarian cancer (PMID:23800275)
• The 3’-UTR of liver mRNA of galectin-1 and RPS4X bind to the HCV NS5B. (PMID:24503063)
• Low RPS4X expression is associated with poor disease-specific and recurrence-free survival in bladder cancer (PMID:25731206)
• lnc-Rps4l-encoded peptide RPS4XL regulates RPS6 phosphorylation and inhibits the proliferation of PASMCs caused by hypoxia. (PMID:33429084)
• Ribosomal Protein S4 X-Linked as a Novel Modulator of MDM2 Stability by Suppressing MDM2 Auto-Ubiquitination and SCF Complex-Mediated Ubiquitination. (PMID:39199272)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps4x	ENSDARG00000014690
rattus_norvegicus	Rps4x	ENSRNOG00000003201
drosophila_melanogaster	RpS4	FBGN0011284
caenorhabditis_elegans		WBGENE00004473

Paralogs (2): RPS4Y1 (ENSG00000129824), RPS4Y2 (ENSG00000280969)

Protein

Protein identifiers

Small ribosomal subunit protein eS4, X isoform — P62701 (reviewed: P62701)

Alternative names: 40S ribosomal protein S4, SCR10, Single copy abundant mRNA protein

All UniProt accessions (2): B2R491, P62701

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. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Similarity. Belongs to the eukaryotic ribosomal protein eS4 family.

RefSeq proteins (1): NP_000998* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000876	Ribosomal_eS4	Family
IPR002942	S4_RNA-bd	Domain
IPR005824	KOW	Domain
IPR013843	Ribosomal_eS4_N	Domain
IPR013845	Ribosomal_eS4_central_region	Domain
IPR014722	Rib_uL2_dom2	Homologous_superfamily
IPR018199	Ribosomal_eS4_N_CS	Conserved_site
IPR032277	Ribosomal_eS4_C	Domain
IPR036986	S4_RNA-bd_sf	Homologous_superfamily
IPR038237	Ribosomal_eS4_central_sf	Homologous_superfamily
IPR041982	Ribosomal_eS4_KOW	Domain

Pfam: PF00467, PF00900, PF08071, PF16121

UniProt features (45 total): strand 23, helix 9, turn 6, sequence conflict 2, initiator methionine 1, chain 1, domain 1, modified residue 1, cross-link 1

Structure

Experimental structures (PDB)

209 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-P62701-F1	95.72	0.97

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 (2): 233, 230

Function

Pathways and Gene Ontology

Reactome pathways

50 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-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
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 234 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_151, GNF2_TPT1, TGACCTY_ERR1_Q2, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CCANNAGRKGGC_UNKNOWN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GNF2_FBL

GO Biological Process (5): cytoplasmic translation (GO:0002181), translation (GO:0006412), positive regulation of cell population proliferation (GO:0008284), ribosomal small subunit biogenesis (GO:0042274), positive regulation of translation (GO:0045727)

GO Molecular Function (4): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), rRNA binding (GO:0019843), protein binding (GO:0005515)

GO Cellular Component (15): nucleoplasm (GO:0005654), cytosol (GO:0005829), ribosome (GO:0005840), focal adhesion (GO:0005925), small ribosomal subunit (GO:0015935), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), small-subunit processome (GO:0032040), cytoplasmic ribonucleoprotein granule (GO:0036464), extracellular exosome (GO:0070062), ribonucleoprotein complex (GO:1990904), nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Translation	2
Nonsense-Mediated Decay (NMD)	2
Ribosome-associated quality control	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
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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
translation	2
ribosome	2
nuclear lumen	2
cytoplasm	2
intracellular membraneless organelle	2
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
nucleic acid binding	1
structural molecule activity	1
RNA binding	1
binding	1
cell-substrate junction	1
ribosomal subunit	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
ribonucleoprotein granule	1
extracellular vesicle	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

343 interactions, top by confidence:

A	B	Type	Score
N	HNRNPR	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
ESR1	TRIM24	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
CASP6	RPS4X	psi-mi:“MI:0915”(physical association)	0.560
RPS4X	CCK	psi-mi:“MI:0915”(physical association)	0.560
RPS4X	DMWD	psi-mi:“MI:0915”(physical association)	0.560
DR1	RPS4X	psi-mi:“MI:0915”(physical association)	0.560
RPS4X	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	RPS4X	psi-mi:“MI:0915”(physical association)	0.560
RPS4X	GSN	psi-mi:“MI:0915”(physical association)	0.560
GTF2B	RPS4X	psi-mi:“MI:0915”(physical association)	0.560
LMNA	RPS4X	psi-mi:“MI:0915”(physical association)	0.560
RAN	RPS4X	psi-mi:“MI:0915”(physical association)	0.560
RPS4X		psi-mi:“MI:0915”(physical association)	0.560
RPS4X	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
SH3GLB1	RPS4X	psi-mi:“MI:0915”(physical association)	0.560
RPS4X	SPRED1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (855): RPS4X (Affinity Capture-MS), RPS4X (Affinity Capture-MS), RPS4X (Affinity Capture-MS), RPS4X (Affinity Capture-MS), RPS4X (Affinity Capture-MS), RPS4X (Affinity Capture-MS), RPS4X (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), RPS4X (Affinity Capture-MS), EIF6 (Co-fractionation), RPL10A (Co-fractionation), RPL17 (Co-fractionation), RPL18 (Co-fractionation), RPL27 (Co-fractionation)

ESM2 similar proteins: A0A1D8PCI6, A4FWA9, A6VGZ7, G1TK17, O22424, O59950, O62738, O62739, P0CX35, P0CX36, P22090, P41042, P46299, P46300, P47836, P47837, P47961, P49204, P49398, P49401, P51405, P62701, P62702, P62703, P62704, P62705, P79103, P79183, P87158, Q0W1X6, Q4GXU6, Q4PMB3, Q56FH2, Q5UAP0, Q642H9, Q6GVM7, Q6PBC4, Q76MY1, Q76N24, Q861U7

Diamond homologs: A0A1D8PCI6, A1RS06, A2BMD1, A3DNB9, A3MWZ7, A4FWA9, A4WLL4, A4YCX8, A5UL76, A6UQ56, A6UWV0, A6VGZ7, A8ACD4, A8MB20, A9A9Q2, B1L778, B1Y9S4, B8D5V8, C3MQ71, C3MVJ0, C3N5T9, C3NEF5, C3NH97, C4KHG8, G1TK17, O05634, O22424, O26123, O28366, O59430, O59950, O62738, O62739, O81363, P0C233, P0CX35, P0CX36, P14023, P22090, P41042

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS4X	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 175 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the ternary complex, and subsequently, the 43S complex	10	17.4×	5e-08
Translation initiation complex formation	11	16.9×	2e-08
Ribosomal scanning and start codon recognition	10	15.3×	1e-07
SARS-CoV-1 modulates host translation machinery	6	14.9×	1e-04
Nuclear RNA decay	6	14.9×	1e-04
Nonsense-Mediated Decay (NMD)	7	13.2×	6e-05
Eukaryotic Translation Initiation	5	12.4×	1e-03
Cap-dependent Translation Initiation	5	12.4×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	5	37.2×	3e-05
translational initiation	10	23.8×	1e-08
mRNA stabilization	8	19.4×	3e-06
mitophagy	7	14.7×	7e-05
stem cell population maintenance	5	13.9×	3e-03
cytoplasmic translation	10	12.3×	3e-06
intrinsic apoptotic signaling pathway	5	11.9×	5e-03
negative regulation of translation	9	11.7×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

729 predictions. Top by Δscore:

Variant	Effect	Δscore
X:72272768:TTGCC:T	acceptor_gain	1.0000
X:72272769:TGCC:T	acceptor_gain	1.0000
X:72272770:GCC:G	acceptor_gain	1.0000
X:72272771:CC:C	acceptor_gain	1.0000
X:72272771:CCC:C	acceptor_gain	1.0000
X:72272772:CC:C	acceptor_gain	1.0000
X:72272773:C:CC	acceptor_gain	1.0000
X:72272773:C:T	acceptor_gain	1.0000
X:72272774:T:A	acceptor_loss	1.0000
X:72273228:TTACC:T	donor_loss	1.0000
X:72273229:TACCT:T	donor_loss	1.0000
X:72273230:A:AC	donor_gain	1.0000
X:72273230:AC:A	donor_gain	1.0000
X:72273231:C:CC	donor_gain	1.0000
X:72273231:C:CG	donor_loss	1.0000
X:72273231:CC:C	donor_gain	1.0000
X:72273231:CCT:C	donor_gain	1.0000
X:72273231:CCTT:C	donor_gain	1.0000
X:72273231:CCTTG:C	donor_gain	1.0000
X:72273385:GTTAC:G	acceptor_gain	1.0000
X:72273386:TTAC:T	acceptor_gain	1.0000
X:72273387:TAC:T	acceptor_gain	1.0000
X:72273388:AC:A	acceptor_gain	1.0000
X:72273389:CC:C	acceptor_gain	1.0000
X:72273390:C:CC	acceptor_gain	1.0000
X:72273391:T:A	acceptor_loss	1.0000
X:72273795:GCTTA:G	donor_loss	1.0000
X:72273796:CTTA:C	donor_loss	1.0000
X:72273797:TTA:T	donor_loss	1.0000
X:72273798:TA:T	donor_loss	1.0000

AlphaMissense

1731 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:72272736:C:G	G243R	1.000
X:72273236:C:A	G229V	1.000
X:72273236:C:T	G229D	1.000
X:72273237:C:G	G229R	1.000
X:72273268:A:C	F218L	1.000
X:72273268:A:T	F218L	1.000
X:72273269:A:G	F218S	1.000
X:72273270:A:G	F218L	1.000
X:72273299:A:T	V208D	1.000
X:72273314:C:T	G203E	1.000
X:72273344:C:T	G193D	1.000
X:72273345:C:G	G193R	1.000
X:72273353:C:A	G190V	1.000
X:72273353:C:T	G190E	1.000
X:72273354:C:G	G190R	1.000
X:72273354:C:T	G190R	1.000
X:72273365:C:A	G186V	1.000
X:72273365:C:T	G186D	1.000
X:72273379:A:C	C181W	1.000
X:72273381:A:G	C181R	1.000
X:72273906:C:G	D143H	1.000
X:72275087:A:G	F109S	1.000
X:72275116:G:C	F99L	1.000
X:72275116:G:T	F99L	1.000
X:72275118:A:G	F99L	1.000
X:72275552:C:A	G85V	1.000
X:72275552:C:T	G85E	1.000
X:72275553:C:G	G85R	1.000
X:72275553:C:T	G85R	1.000
X:72275642:G:T	A55D	1.000

dbSNP variants (sampled 300 via entrez): RS1000214249 (X:72276733 C>A), RS1000554984 (X:72278199 G>A), RS1000646820 (X:72277881 T>A), RS1000825369 (X:72273162 G>A), RS1001101562 (X:72272850 CTCACT>C), RS1001992819 (X:72278832 T>C), RS1004051365 (X:72276306 C>T), RS1004445758 (X:72276901 T>C,G), RS1005041559 (X:72274410 T>A), RS1005160892 (X:72277465 C>T), RS1005480600 (X:72277750 A>G), RS1006459261 (X:72271935 T>A,C,G), RS1006737465 (X:72271901 G>C), RS1007242061 (X:72271560 G>A), RS1007571222 (X:72277102 C>T)

Disease associations

OMIM: gene MIM:312760 | 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
GCST012466_5	Autism spectrum disorder	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066851 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

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

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

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

ChEMBL bioactivities

51 potent at pChembl≥5 of 55 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.53	Kd	29.63	nM	CHEMBL3752910
7.53	ED50	29.63	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
6.29	Kd	514.8	nM	CHEMBL5653589
6.29	ED50	514.8	nM	CHEMBL5653589
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
5.13	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
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

49 with measured affinity, of 215 total; 29 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	2149307: Binding affinity to human RPS4X incubated for 45 mins by Kinobead based pull down assay	kd	0.0296	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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149307: Binding affinity to human RPS4X incubated for 45 mins by Kinobead based pull down assay	kd	0.5148	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
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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178964: Inhibition of RPS4X (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression, affects cotreatment, increases methylation, decreases expression	4
Arsenic	decreases expression, increases abundance, increases expression	2
Cisplatin	increases expression, increases response to substance	2
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	increases reaction, affects binding	1
3,3’-diindolylmethane	increases expression, increases reaction	1
sodium arsenite	increases expression, increases abundance	1
tetrabromobisphenol A	decreases expression	1
bleomycetin	decreases expression	1
epigallocatechin gallate	decreases expression	1
arsenic trichloride	decreases expression, increases abundance	1
4-hydroxy-equilenin	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases secretion	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
bisphenol S	increases expression	1
jinfukang	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1

ChEMBL screening assays

96 unique, capped per target: 96 binding

Representative assays (with source publication via chembl_document):

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

Clinical trials (associated diseases)

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