RPS25
gene geneOn this page
Also known as S25eS25
Summary
RPS25 (ribosomal protein S25, HGNC:10413) is a protein-coding gene on chromosome 11q23.3, encoding Small ribosomal subunit protein eS25 (P62851). Component of the small ribosomal subunit. It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).
Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S25E 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 6230 — RefSeq curated summary.
At a glance
- Clinical variants (ClinVar): 12 total
- Druggable target: yes — 1 molecules with ChEMBL bioactivity
- Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
- MANE Select transcript:
NM_001028
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:10413 |
| Approved symbol | RPS25 |
| Name | ribosomal protein S25 |
| Location | 11q23.3 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | S25, eS25 |
| Ensembl gene | ENSG00000118181 |
| Ensembl biotype | protein_coding |
| OMIM | 180465 |
| Entrez | 6230 |
Gene structure
Transcript identifiers
Ensembl transcripts: 15 — 10 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined
ENST00000524864, ENST00000527673, ENST00000527791, ENST00000527853, ENST00000528547, ENST00000532567, ENST00000891654, ENST00000891655, ENST00000937795, ENST00000937796, ENST00000937797, ENST00000937798, ENST00000937799, ENST00000937800, ENST00000942362
RefSeq mRNA: 1 — MANE Select: NM_001028
NM_001028
CCDS: CCDS8406
Canonical transcript exons
ENST00000527673 — 5 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001275591 | 119017958 | 119018053 |
| ENSE00002144944 | 119018282 | 119018343 |
| ENSE00003480940 | 119017362 | 119017545 |
| ENSE00003512878 | 119015841 | 119015939 |
| ENSE00003849338 | 119015717 | 119015758 |
Expression profiles
Bgee: expression breadth ubiquitous, 134 present calls, max score 99.94.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1453.2492 / max 17964.4060, expressed in 1827 samples.
FANTOM5 promoters (4 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 122655 | 1442.4437 | 1827 |
| 122656 | 9.2577 | 1671 |
| 122654 | 1.4087 | 655 |
| 122653 | 0.1390 | 38 |
Top tissues by expression
134 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| left ovary | UBERON:0002119 | 99.94 | gold quality |
| ovary | UBERON:0000992 | 99.93 | gold quality |
| right ovary | UBERON:0002118 | 99.93 | gold quality |
| pituitary gland | UBERON:0000007 | 99.92 | gold quality |
| right uterine tube | UBERON:0001302 | 99.92 | gold quality |
| adenohypophysis | UBERON:0002196 | 99.92 | gold quality |
| calcaneal tendon | UBERON:0003701 | 99.92 | gold quality |
| mucosa of stomach | UBERON:0001199 | 99.91 | gold quality |
| fallopian tube | UBERON:0003889 | 99.91 | gold quality |
| lymph node | UBERON:0000029 | 99.90 | gold quality |
| endocervix | UBERON:0000458 | 99.90 | gold quality |
| right lobe of thyroid gland | UBERON:0001119 | 99.90 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 99.90 | gold quality |
| right coronary artery | UBERON:0001625 | 99.90 | gold quality |
| thyroid gland | UBERON:0002046 | 99.90 | gold quality |
| subcutaneous adipose tissue | UBERON:0002190 | 99.90 | gold quality |
| thoracic mammary gland | UBERON:0005200 | 99.90 | gold quality |
| adipose tissue | UBERON:0001013 | 99.89 | gold quality |
| left uterine tube | UBERON:0001303 | 99.89 | gold quality |
| popliteal artery | UBERON:0002250 | 99.89 | gold quality |
| tibial artery | UBERON:0007610 | 99.89 | gold quality |
| omental fat pad | UBERON:0010414 | 99.89 | gold quality |
| ectocervix | UBERON:0012249 | 99.89 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 99.89 | gold quality |
| fundus of stomach | UBERON:0001160 | 99.88 | gold quality |
| tibial nerve | UBERON:0001323 | 99.88 | gold quality |
| ascending aorta | UBERON:0001496 | 99.88 | gold quality |
| thoracic aorta | UBERON:0001515 | 99.88 | gold quality |
| left coronary artery | UBERON:0001626 | 99.88 | gold quality |
| gall bladder | UBERON:0002110 | 99.88 | gold quality |
Single-cell (SCXA)
Detected in 11 experiment(s), a significant marker in 5.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-MTAB-6678 | yes | 39.82 |
| E-MTAB-9067 | yes | 29.03 |
| E-HCAD-35 | yes | 7.86 |
| E-MTAB-9801 | yes | 6.09 |
| E-GEOD-70580 | no | 1464.62 |
| E-CURD-97 | no | 1415.16 |
| E-GEOD-76312 | no | 1253.26 |
| E-MTAB-6075 | no | 936.65 |
| E-MTAB-9388 | no | 808.77 |
| E-MTAB-7606 | no | 681.45 |
| E-ANND-3 | no | 0.00 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): TP53
Functional genomics
DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.
Literature-anchored findings (GeneRIF, showing 4)
- data demonstrate that ribosomal protein S25 is a novel regulator of the MDM2-p53 circuit in ribosomal stress; results shed light on biological consequences of RP-MDM2-p53 interplay and also reveal the existence of a novel S25-p53 feedback regulatory loop (PMID:22777350)
- HBZ induces nuclear retention of RPS25 mRNA in the nucleus and loss of RPS25 protein expression. Inhibition of RPS25 expression stimulates Delta JunD synthesis. (PMID:28260789)
- We performed a genetic screen for regulators of RAN translation and identified small ribosomal protein subunit 25 (RPS25), presenting a potential therapeutic target for C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia and other neurodegenerative diseases caused by nucleotide repeat expansions. (PMID:31358992)
- A memory of eS25 loss drives resistance phenotypes. (PMID:32463448)
Cross-species orthologs
4 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | rps25 | ENSDARG00000041811 |
| rattus_norvegicus | Rps25l3 | ENSRNOG00000062325 |
| drosophila_melanogaster | RpS25 | FBGN0086472 |
| caenorhabditis_elegans | WBGENE00004494 |
Protein
Protein identifiers
Small ribosomal subunit protein eS25 — P62851 (reviewed: P62851)
Alternative names: 40S ribosomal protein S25
All UniProt accessions (3): P62851, E9PK60, E9PQK3
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.
Subunit / interactions. Component of the small ribosomal subunit.
Subcellular location. Cytoplasm.
Similarity. Belongs to the eukaryotic ribosomal protein eS25 family.
RefSeq proteins (1): NP_001019* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR004977 | Ribosomal_eS25 | Family |
| IPR036388 | WH-like_DNA-bd_sf | Homologous_superfamily |
Pfam: PF03297
UniProt features (19 total): modified residue 7, strand 4, helix 4, compositionally biased region 2, chain 1, region of interest 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-P62851-F1 | 74.36 | 0.34 |
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 (7): 94, 43, 52, 52, 60, 66, 94
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: 225 (showing top):
GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, MODULE_151, MORF_UBE2I, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, HSIAO_HOUSEKEEPING_GENES, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_TRANSLATION, MARTINEZ_RB1_TARGETS_DN, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GNF2_FBL, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, ACTTTAT_MIR1425P
GO Biological Process (4): cytoplasmic translation (GO:0002181), rRNA processing (GO:0006364), translation (GO:0006412), ribosomal small subunit biogenesis (GO:0042274)
GO Molecular Function (3): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)
GO Cellular Component (13): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), ribosome (GO:0005840), postsynaptic density (GO:0014069), small ribosomal subunit (GO:0015935), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), extracellular exosome (GO:0070062), synapse (GO:0045202), ribonucleoprotein complex (GO:1990904)
Reactome top-level categories
Rollup of top-14 pathways:
| Category | Pathways |
|---|---|
| Cap-dependent Translation Initiation | 4 |
| Translation | 2 |
| 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 | 3 |
| ribosome biogenesis | 2 |
| ribosome | 2 |
| nuclear lumen | 2 |
| intracellular membraneless organelle | 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 |
| binding | 1 |
| intracellular membrane-bounded organelle | 1 |
| intracellular anatomical structure | 1 |
| cytoplasm | 1 |
| asymmetric synapse | 1 |
| postsynaptic specialization | 1 |
| ribosomal subunit | 1 |
| cytosol | 1 |
| small ribosomal subunit | 1 |
| cytosolic ribosome | 1 |
| extracellular vesicle | 1 |
| cell junction | 1 |
| protein-containing complex | 1 |
Protein interactions and networks
STRING
0 interactions, top by confidence (×1000):
IntAct
280 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| CFTR | ESYT2 | psi-mi:“MI:0914”(association) | 0.710 |
| NCBP2 | KPNA3 | psi-mi:“MI:0914”(association) | 0.640 |
| RACK1 | RPS17 | psi-mi:“MI:0915”(physical association) | 0.610 |
| THAP1 | RPS25 | psi-mi:“MI:0915”(physical association) | 0.560 |
| RPS25 | THAP1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| RPS25 | TSPYL2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| RPS25 | psi-mi:“MI:0915”(physical association) | 0.560 | |
| ZBTB14 | RPS25 | psi-mi:“MI:0915”(physical association) | 0.560 |
| RPS25 | HMBOX1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| RPS25 | STAC3 | psi-mi:“MI:0915”(physical association) | 0.560 |
| RPS25 | NKAPD1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| RPS25 | E7 | psi-mi:“MI:0915”(physical association) | 0.550 |
| RPL13 | RPLP1 | psi-mi:“MI:0914”(association) | 0.530 |
| RPS3 | ZNF316 | psi-mi:“MI:0914”(association) | 0.530 |
| CFTR | PLEKHG3 | psi-mi:“MI:0914”(association) | 0.480 |
| ESR2 | FBLL1 | psi-mi:“MI:0914”(association) | 0.460 |
| FUS | DDX3X | psi-mi:“MI:0914”(association) | 0.430 |
| MAP3K4 | RPS25 | psi-mi:“MI:0915”(physical association) | 0.400 |
| RPS25 | RPS5 | psi-mi:“MI:0915”(physical association) | 0.400 |
| RPS25 | RPS19 | psi-mi:“MI:0915”(physical association) | 0.400 |
BioGRID (606): RPS25 (Affinity Capture-MS), THAP1 (Two-hybrid), RPS25 (Affinity Capture-MS), RPS25 (Affinity Capture-MS), RPS25 (Affinity Capture-MS), RPS25 (Affinity Capture-MS), RPS25 (Affinity Capture-MS), FAU (Co-fractionation), HNRNPU (Co-fractionation), RPL10 (Co-fractionation), RPL10A (Co-fractionation), RPL12 (Co-fractionation), RPL13 (Co-fractionation), RPL13A (Co-fractionation), RPL15 (Co-fractionation)
ESM2 similar proteins: A0A1D8PNQ6, G1TDB3, J9PAS6, O61749, O74172, P05749, P09132, P0C0T4, P0CX49, P0CX50, P14327, P34264, P37164, P37165, P48588, P49181, P52821, P56628, P62851, P62852, P62853, P79009, Q03409, Q09817, Q3E792, Q3ZBG7, Q4WX89, Q54VN6, Q54VZ4, Q56JX5, Q5B8Y4, Q5RBR1, Q6FPX5, Q6PBI5, Q6Q311, Q75DJ1, Q7SC06, Q8AVP1, Q8ISN9, Q8STD9
Diamond homologs: A0A1D8PNQ6, G1TDB3, O74172, P0C0T4, P46301, P48588, P52821, P62851, P62852, P62853, P79009, Q03409, Q3E792, Q56JX5, Q6FPX5, Q6PBI5, Q6Q311, Q75DJ1, Q7SC06, Q8GYL5, Q8ISN9, Q90YP9, Q94G66, Q962Q5, Q9N9V4, Q9SIK2, Q9SIW5, Q9T029, Q975P8, Q97ZZ6, Q8STD9
SIGNOR signaling
1 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| RPS25 | “form complex” | “40S cytosolic small ribosomal subunit” | binding |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 194 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 |
|---|---|---|---|
| Eukaryotic Translation Initiation | 9 | 20.7× | 8e-09 |
| Cap-dependent Translation Initiation | 9 | 20.7× | 8e-09 |
| SARS-CoV-1 modulates host translation machinery | 9 | 20.7× | 8e-09 |
| Formation of the ternary complex, and subsequently, the 43S complex | 12 | 19.3× | 3e-11 |
| Eukaryotic Translation Elongation | 9 | 18.7× | 2e-08 |
| Ribosomal scanning and start codon recognition | 13 | 18.5× | 6e-12 |
| Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S | 9 | 18.3× | 2e-08 |
| Nonsense-Mediated Decay (NMD) | 10 | 17.4× | 6e-09 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| cytoplasmic translation | 20 | 21.8× | 2e-18 |
| stress granule assembly | 5 | 17.7× | 9e-04 |
| translational initiation | 8 | 16.9× | 5e-06 |
| ribosomal small subunit biogenesis | 10 | 13.4× | 1e-06 |
| ribosomal large subunit biogenesis | 5 | 13.0× | 4e-03 |
| mRNA stabilization | 6 | 12.9× | 8e-04 |
| stem cell population maintenance | 5 | 12.4× | 4e-03 |
| translation | 20 | 12.1× | 2e-13 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
12 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 3 |
| Likely benign | 0 |
| Benign | 1 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
573 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 11:119015936:AGTC:A | acceptor_gain | 1.0000 |
| 11:119015937:GTCC:G | acceptor_loss | 1.0000 |
| 11:119015938:TC:T | acceptor_gain | 1.0000 |
| 11:119015939:CC:C | acceptor_gain | 1.0000 |
| 11:119015940:C:CC | acceptor_gain | 1.0000 |
| 11:119015940:CT:C | acceptor_loss | 1.0000 |
| 11:119015941:T:G | acceptor_loss | 1.0000 |
| 11:119017356:CCTCA:C | donor_loss | 1.0000 |
| 11:119017357:CTCA:C | donor_loss | 1.0000 |
| 11:119017358:TCA:T | donor_loss | 1.0000 |
| 11:119017360:ACCTT:A | donor_loss | 1.0000 |
| 11:119017541:CACTT:C | acceptor_gain | 1.0000 |
| 11:119017551:C:CT | acceptor_gain | 1.0000 |
| 11:119017554:C:T | acceptor_gain | 1.0000 |
| 11:119017960:T:A | donor_gain | 1.0000 |
| 11:119018277:CTTA:C | donor_loss | 1.0000 |
| 11:119018280:A:AC | donor_gain | 1.0000 |
| 11:119018281:C:CC | donor_gain | 1.0000 |
| 11:119018281:C:CG | donor_loss | 1.0000 |
| 11:119015532:TTTCA:T | acceptor_loss | 0.9900 |
| 11:119015533:TTCA:T | acceptor_loss | 0.9900 |
| 11:119015534:TCA:T | acceptor_loss | 0.9900 |
| 11:119015535:CAG:C | acceptor_loss | 0.9900 |
| 11:119015536:A:AC | acceptor_loss | 0.9900 |
| 11:119015536:A:AG | acceptor_gain | 0.9900 |
| 11:119015537:G:GG | acceptor_gain | 0.9900 |
| 11:119015537:GAC:G | acceptor_gain | 0.9900 |
| 11:119015935:AAGTC:A | acceptor_gain | 0.9900 |
| 11:119015937:GTC:G | acceptor_gain | 0.9900 |
| 11:119017361:CCT:C | donor_gain | 0.9900 |
AlphaMissense
807 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 11:119015890:T:A | R111S | 1.000 |
| 11:119015890:T:G | R111S | 1.000 |
| 11:119015891:C:A | R111I | 1.000 |
| 11:119015900:A:T | I108N | 1.000 |
| 11:119017373:A:G | L91P | 1.000 |
| 11:119017385:G:T | A87D | 1.000 |
| 11:119017394:G:T | A84D | 1.000 |
| 11:119017397:A:G | L83P | 1.000 |
| 11:119017403:C:T | G81D | 1.000 |
| 11:119017404:C:G | G81R | 1.000 |
| 11:119017409:A:T | I79N | 1.000 |
| 11:119017411:C:A | K78N | 1.000 |
| 11:119017411:C:G | K78N | 1.000 |
| 11:119017413:T:C | K78E | 1.000 |
| 11:119017415:A:G | L77P | 1.000 |
| 11:119017417:T:A | R76S | 1.000 |
| 11:119017417:T:G | R76S | 1.000 |
| 11:119017418:C:A | R76I | 1.000 |
| 11:119017418:C:G | R76T | 1.000 |
| 11:119017421:T:A | E75V | 1.000 |
| 11:119017422:C:T | E75K | 1.000 |
| 11:119017424:G:A | S74F | 1.000 |
| 11:119017427:A:T | V73D | 1.000 |
| 11:119017433:G:T | A71D | 1.000 |
| 11:119017439:G:A | T69I | 1.000 |
| 11:119017442:A:C | I68R | 1.000 |
| 11:119017442:A:T | I68K | 1.000 |
| 11:119017445:A:G | L67P | 1.000 |
| 11:119017447:T:A | K66N | 1.000 |
| 11:119017447:T:G | K66N | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000121364 (11:119015770 A>G), RS1000708180 (11:119019907 A>G), RS1000730956 (11:119017219 G>A,C,T), RS1001022384 (11:119018706 G>A,C,T), RS1001474460 (11:119018506 A>G), RS1001527529 (11:119017265 T>A,C), RS1001558402 (11:119017693 A>G), RS1001746295 (11:119016060 G>A), RS1003027653 (11:119016902 G>A,C), RS1003273212 (11:119018458 A>C,T), RS1004842040 (11:119017305 T>C), RS1004952670 (11:119016710 C>G), RS1005472286 (11:119018497 A>G), RS1006280700 (11:119018234 A>G), RS1008132113 (11:119016597 C>A,T)
Disease associations
OMIM: gene MIM:180465 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
0 associations (top):
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067565 (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 |
|---|---|---|---|---|
| 6.70 | Kd | 200.1 | nM | CHEMBL5653589 |
| 6.70 | ED50 | 200.1 | nM | CHEMBL5653589 |
| 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 |
| 5.58 | Kd | 2635 | nM | CHEMBL3752910 |
| 5.58 | ED50 | 2635 | nM | CHEMBL3752910 |
| 5.55 | IC50 | 2820 | nM | CHEMBL4127458 |
| 5.53 | IC50 | 2970 | nM | CHEMBL4127311 |
| 5.51 | IC50 | 3080 | nM | CHEMBL4126072 |
| 5.46 | IC50 | 3500 | nM | CHEMBL4525277 |
| 5.44 | IC50 | 3630 | nM | CHEMBL4469712 |
| 5.39 | IC50 | 4100 | nM | CHEMBL4128560 |
| 5.37 | IC50 | 4300 | nM | CHEMBL4127016 |
| 5.36 | IC50 | 4380 | nM | CHEMBL4527910 |
| 5.16 | IC50 | 7000 | nM | CHEMBL4109308 |
| 5.13 | IC50 | 7400 | nM | CHLORAMPHENICOL SULFATE SALT |
| 5.09 | IC50 | 8040 | nM | CHEMBL4128250 |
| 5.08 | IC50 | 8370 | nM | CHEMBL4128250 |
| 5.03 | IC50 | 9320 | nM | CHEMBL4127016 |
| 5.03 | IC50 | 9240 | nM | CHEMBL4128560 |
PubChem BioAssay actives
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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2149298: Binding affinity to human RPS25 incubated for 45 mins by Kinobead based pull down assay | kd | 0.2001 | 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 |
| 4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2149298: Binding affinity to human RPS25 incubated for 45 mins by Kinobead based pull down assay | kd | 2.6350 | uM |
| N-(3-chloro-2-pyridinyl)-4-(6-methylpyrazin-2-yl)-N-[(3R)-piperidin-3-yl]benzamide | 1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA | ic50 | 2.8200 | uM |
| N-(3-chloro-2-pyridinyl)-4-[6-(dimethylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide | 1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA | ic50 | 2.9700 | uM |
| N-(3-chloro-2-pyridinyl)-4-[6-(methylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide | 1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA | ic50 | 3.0800 | uM |
| N-isoquinolin-1-yl-4-(6-methyl-1,2-benzoxazol-3-yl)-N-[(3R)-piperidin-3-yl]piperazine-1-carboxamide | 1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay | ic50 | 3.5000 | uM |
| N-(3-methylpyrazin-2-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide | 1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay | ic50 | 3.6300 | uM |
| N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-6-(triazolo[4,5-b]pyridin-3-yl)pyridine-3-carboxamide | 1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay | ic50 | 4.1000 | uM |
| N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazin-2-ylbenzamide | 1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay | ic50 | 4.3000 | uM |
| 4-(2-fluorophenyl)-N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide | 1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay | ic50 | 4.3800 | uM |
| 2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide;sulfuric acid | 717551: Inhibition of mitochondrial ribosome-mediated protein synthesis in human HeLa cells assessed as {35S]methionine incorporation by autoradiography | ic50 | 7.4000 | uM |
CTD chemical–gene interactions
47 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| sodium arsenite | decreases expression, increases activity, increases abundance | 5 |
| bisphenol A | decreases expression | 2 |
| Arsenic Trioxide | decreases expression, increases expression | 2 |
| Arsenic | affects cotreatment, decreases expression, increases abundance | 2 |
| bisphenol F | increases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| pyrogallol 1,3-dimethyl ether | affects cotreatment, affects localization, increases expression | 1 |
| arsenite | affects binding, increases reaction | 1 |
| methylparaben | decreases expression | 1 |
| perfluorooctanoic acid | decreases expression | 1 |
| arsenic trichloride | affects cotreatment, decreases expression, increases abundance | 1 |
| azoxystrobin | increases expression | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| deguelin | increases expression | 1 |
| fenpyroximate | increases expression | 1 |
| 4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide | 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 |
| pyrimidifen | increases expression | 1 |
| ICG 001 | decreases expression | 1 |
| bisphenol B | increases expression | 1 |
| pyrachlostrobin | increases expression | 1 |
| hexabrominated diphenyl ether 153 | decreases expression | 1 |
| bisphenol S | increases expression | 1 |
| LDN 193189 | affects cotreatment, decreases expression | 1 |
| picoxystrobin | increases expression | 1 |
| Resveratrol | affects cotreatment, decreases expression | 1 |
| Acetaminophen | decreases expression | 1 |
| Antimycin A | increases expression | 1 |
| Benzo(a)pyrene | increases expression | 1 |
| Copper | affects cotreatment, decreases expression, increases abundance | 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 |
Cellosaurus cell lines
2 cell lines: 2 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_TJ58 | HAP1 RPS25 (-) 1 | Cancer cell line | Male |
| CVCL_TJ59 | HAP1 RPS25 (-) 2 | Cancer cell line | Male |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.