RPS27

gene
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Also known as MPS-1MPS1S27eS27

Summary

RPS27 (ribosomal protein S27, HGNC:10416) is a protein-coding gene on chromosome 1q21.3, encoding Small ribosomal subunit protein eS27 (P42677). Component of the small ribosomal subunit.

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the S27e family of ribosomal proteins and component of the 40S subunit. The encoded protein contains a C4-type zinc finger domain that can bind to zinc and may bind to nucleic acid. Mutations in this gene have been identified in numerous melanoma patients and in at least one patient with Diamond-Blackfan anemia (DBA). Elevated expression of this gene has been observed in various human cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6232 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): Diamond-Blackfan anemia 17 (Limited, GenCC)
  • GWAS associations: 12
  • Clinical variants (ClinVar): 13 total
  • Phenotypes (HPO): 62
  • Druggable target: yes — 1 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_001030

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:10416
Approved symbolRPS27
Nameribosomal protein S27
Location1q21.3
Locus typegene with protein product
StatusApproved
AliasesMPS-1, MPS1, S27, eS27
Ensembl geneENSG00000177954
Ensembl biotypeprotein_coding
OMIM603702
Entrez6232

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000392558, ENST00000477151, ENST00000493224, ENST00000643794, ENST00000651669, ENST00000936803, ENST00000936804, ENST00000936805, ENST00000936806

RefSeq mRNA: 3 — MANE Select: NM_001030 NM_001030, NM_001349946, NM_001349947

CCDS: CCDS1059

Canonical transcript exons

ENST00000651669 — 4 exons

ExonStartEnd
ENSE00003468875153991566153991676
ENSE00003669489153992065153992155
ENSE00003688128153991115153991223
ENSE00003844361153990762153990802

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 822.6043 / max 9213.7604, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
5463821.96581827
54640.6384337

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
ganglionic eminenceUBERON:000402399.99gold quality
granulocyteCL:000009499.98gold quality
lymph nodeUBERON:000002999.98gold quality
endocervixUBERON:000045899.98gold quality
right ovaryUBERON:000211899.98gold quality
left ovaryUBERON:000211999.98gold quality
ovaryUBERON:000099299.97gold quality
corpus callosumUBERON:000233699.97gold quality
ventricular zoneUBERON:000305399.97gold quality
calcaneal tendonUBERON:000370199.97gold quality
fallopian tubeUBERON:000388999.97gold quality
cortical plateUBERON:000534399.97gold quality
body of uterusUBERON:000985399.97gold quality
ectocervixUBERON:001224999.97gold quality
pituitary glandUBERON:000000799.96gold quality
zone of skinUBERON:000001499.96gold quality
vaginaUBERON:000099699.96gold quality
adipose tissueUBERON:000101399.96gold quality
right lobe of thyroid glandUBERON:000111999.96gold quality
left lobe of thyroid glandUBERON:000112099.96gold quality
mucosa of stomachUBERON:000119999.96gold quality
right uterine tubeUBERON:000130299.96gold quality
left uterine tubeUBERON:000130399.96gold quality
skin of abdomenUBERON:000141699.96gold quality
skin of legUBERON:000151199.96gold quality
thyroid glandUBERON:000204699.96gold quality
spleenUBERON:000210699.96gold quality
subcutaneous adipose tissueUBERON:000219099.96gold quality
thoracic mammary glandUBERON:000520099.96gold quality
myometriumUBERON:000129699.95gold quality

Single-cell (SCXA)

Detected in 70 experiment(s), a significant marker in 21.

ExperimentMarker?Max mean expression
E-MTAB-6701yes20879.66
E-MTAB-7407yes18085.64
E-CURD-88yes17943.85
E-CURD-46yes17717.83
E-HCAD-1yes17324.87
E-MTAB-9067yes17281.51
E-HCAD-9yes16945.99
E-MTAB-8410yes16161.81
E-MTAB-9221yes15971.65
E-CURD-122yes15331.42
E-GEOD-135922yes12764.27
E-CURD-98yes7886.73
E-MTAB-10042yes7379.03
E-MTAB-7316yes6700.47
E-MTAB-10855yes4958.33

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 16)

  • MPS-1 was overexpressed in 86% of the gastric cancer tissues and all gastric cancer cells. MPS-1 expression was significantly increased and corresponded with the tumor-node-metastasis clinical stage, and was significantly higher in the late stage. (PMID:16914586)
  • When MPS-1 is overexpressed, it has an extraribosomal function as a strong inhibitor of HNSCC tumor cell growth, which may be exerted by reduced paxillin gene expression. (PMID:19642098)
  • study reveals a multilevel interplay between RPS27L/S27 and p53-MDM2 axis, with RPS27L functioning as a p53 target, a MDM2 substrate and a p53 regulator (PMID:21170087)
  • This work is consistent with a critical role of RPMPS-1/S27 in the life cycle of various viruses and shows that disruption of viral ZFPs is potentially important to control and prevent deathly viral diseases (PMID:21518817)
  • a novel pathway, the MPS-1/NF-kappaB/Gadd45beta signal pathway, played an important role in MPS-1 knockdown-induced apoptosis of gastric cancer cells. (PMID:21796632)
  • The data on genome context analysis indicates that the presence of MPS-1 in the blood is an indicator of oncogenesis (PMID:22798506)
  • We identified frequent recurrent (i.e. hotspot) mutation in the 5’ untranslated region of RPS27 in ~10% of melanoma samples (PMID:24913145)
  • Loss of function mutations in RPL27 and RPS27 lead to Diamond-Blackfan anaemia. (PMID:25424902)
  • MPS1 is a new marker of Purkinje Cells. (PMID:26708598)
  • reveal how Mps1 dynamically modifies kinetochores to correct improper attachments and ensure faithful chromosome segregation (PMID:28441529)
  • Chloride anion behaves as a signaling effector for CFTR in the modulation of RPS27 expression. (PMID:28941802)
  • this study indicates that MPS-1 promotes leptin-induced colorectal cancer (CRC) via activating JNK/c-Jun pathway. MPS-1 might represent a potent candidate for the treatment and prognostic prediction of obesity-associated CRC. (PMID:31506433)
  • Functional analysis of RPS27 mutations and expression in melanoma. (PMID:31663663)
  • Neddylation modification of ribosomal protein RPS27L or RPS27 by MDM2 or NEDP1 regulates cancer cell survival. (PMID:32779270)
  • Hsp90 chaperone code and the tumor suppressor VHL cooperatively regulate the mitotic checkpoint. (PMID:34586601)
  • RPS27 selectively regulates the expression and alternative splicing of inflammatory and immune response genes in thyroid cancer cells. (PMID:35546566)

Cross-species orthologs

1 orthologs

OrganismSymbolGene ID
rattus_norvegicusENSRNOG00000070133

Paralogs (1): RPS27L (ENSG00000185088)

Protein

Protein identifiers

Small ribosomal subunit protein eS27P42677 (reviewed: P42677)

Alternative names: 40S ribosomal protein S27, Metallopan-stimulin 1

All UniProt accessions (2): A0A2R8Y731, P42677

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. Required for proper rRNA processing and maturation of 18S rRNAs. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.

Subunit / interactions. Component of the small ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Tissue specificity. Expressed in a wide variety of actively proliferating cells and tumor tissues.

Disease relevance. Diamond-Blackfan anemia 17 (DBA17) [MIM:617409] An autosomal dominant form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the eukaryotic ribosomal protein eS27 family.

RefSeq proteins (3): NP_001021, NP_001336875, NP_001336876 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000592Ribosomal_eS27Family
IPR011332Ribosomal_zn-bdHomologous_superfamily
IPR023407Ribosomal_eS27_Zn-bd_dom_sfHomologous_superfamily

Pfam: PF01667

UniProt features (23 total): strand 10, binding site 4, helix 2, initiator methionine 1, chain 1, sequence conflict 1, zinc finger region 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

214 structures, top 30 by resolution.

PDBMethodResolution (Å)
8GLPELECTRON MICROSCOPY1.67
8QOIELECTRON MICROSCOPY1.9
9O3WELECTRON MICROSCOPY1.9
8YOOELECTRON MICROSCOPY2
9C3HELECTRON MICROSCOPY2
7R4XELECTRON MICROSCOPY2.15
9I2DELECTRON MICROSCOPY2.19
9PBEELECTRON MICROSCOPY2.19
8YOPELECTRON MICROSCOPY2.2
9O3VELECTRON MICROSCOPY2.2
9O3YELECTRON MICROSCOPY2.2
8JDKELECTRON MICROSCOPY2.26
8G5YELECTRON MICROSCOPY2.29
9S3DELECTRON MICROSCOPY2.32
9RPVELECTRON MICROSCOPY2.35
9S3BELECTRON MICROSCOPY2.38
8K2CELECTRON MICROSCOPY2.4
8XSXELECTRON MICROSCOPY2.4
9SPFELECTRON MICROSCOPY2.4
9SPIELECTRON MICROSCOPY2.4
8JDLELECTRON MICROSCOPY2.42
9S3CELECTRON MICROSCOPY2.42
9QLOELECTRON MICROSCOPY2.47
9P8BELECTRON MICROSCOPY2.48
7XNYELECTRON MICROSCOPY2.5
8JDJELECTRON MICROSCOPY2.5
9RUCELECTRON MICROSCOPY2.5
8G60ELECTRON MICROSCOPY2.54
8IFEELECTRON MICROSCOPY2.57
9P7DELECTRON MICROSCOPY2.57

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P42677-F192.470.88

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 37; 40; 56; 59

Post-translational modifications (1): 11

Function

Pathways and Gene Ontology

Reactome pathways

68 pathways

IDPathway
R-HSA-141444Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-156827L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-156902Peptide chain elongation
R-HSA-1799339SRP-dependent cotranslational protein targeting to membrane
R-HSA-192823Viral mRNA Translation
R-HSA-2408557Selenocysteine synthesis
R-HSA-2467813Separation of Sister Chromatids
R-HSA-2500257Resolution of Sister Chromatid Cohesion
R-HSA-5663220RHO GTPases Activate Formins
R-HSA-6791226Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-68877Mitotic Prometaphase
R-HSA-72649Translation initiation complex formation
R-HSA-72689Formation of a pool of free 40S subunits
R-HSA-72695Formation of the ternary complex, and subsequently, the 43S complex
R-HSA-72702Ribosomal scanning and start codon recognition
R-HSA-72706GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-72764Eukaryotic Translation Termination
R-HSA-9010553Regulation of expression of SLITs and ROBOs
R-HSA-9633012Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-9648025EML4 and NUDC in mitotic spindle formation
R-HSA-9735869SARS-CoV-1 modulates host translation machinery
R-HSA-9754678SARS-CoV-2 modulates host translation machinery
R-HSA-975956Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
R-HSA-975957Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-9954714PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA
R-HSA-9954716ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA
R-HSA-1266738Developmental Biology
R-HSA-141424Amplification of signal from the kinetochores
R-HSA-1430728Metabolism
R-HSA-156842Eukaryotic Translation Elongation

MSigDB gene sets: 454 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RIBOSOME_BIOGENESIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_151, GNF2_TPT1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, HSIAO_HOUSEKEEPING_GENES, GOBP_RIBOSOME_ASSEMBLY, GGCNKCCATNK_UNKNOWN, GOBP_TRANSLATION, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION

GO Biological Process (5): ribosomal small subunit assembly (GO:0000028), cytoplasmic translation (GO:0002181), rRNA processing (GO:0006364), translation (GO:0006412), ribosomal small subunit biogenesis (GO:0042274)

GO Molecular Function (6): DNA binding (GO:0003677), RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (14): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), ribosome (GO:0005840), postsynaptic density (GO:0014069), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), small-subunit processome (GO:0032040), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), nucleolus (GO:0005730), cytoplasm (GO:0005737), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-15 pathways:

CategoryPathways
Cap-dependent Translation Initiation4
Translation2
Mitotic Prometaphase2
Amplification of signal from the kinetochores1
Eukaryotic Translation Initiation1
Eukaryotic Translation Elongation1
Influenza Viral RNA Transcription and Replication1
Selenoamino acid metabolism1
Mitotic Anaphase1
RHO GTPase Effectors1
rRNA processing in the nucleus and cytosol1
M Phase1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S1
Signaling by ROBO receptors1
Cellular response to starvation1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
synapse3
ribosome biogenesis2
nucleic acid binding2
ribosome2
nuclear lumen2
intracellular membraneless organelle2
protein-RNA complex assembly1
ribosome assembly1
ribosomal small subunit biogenesis1
translation1
RNA processing1
rRNA metabolic process1
peptidyltransferase activity1
translational initiation1
translational elongation1
translational termination1
macromolecule biosynthetic process1
protein metabolic process1
protein biosynthetic process1
ribonucleoprotein complex biogenesis1
structural molecule activity1
transition metal ion binding1
binding1
cation binding1
intracellular membrane-bounded organelle1
cytoplasm1
asymmetric synapse1
postsynaptic specialization1
cytosol1
small ribosomal subunit1
cytosolic ribosome1
nucleolus1
preribosome1
t-UTP complex1
nuclear protein-containing complex1
intracellular anatomical structure1
protein-containing complex1

Protein interactions and networks

STRING

3092 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
RPS27RPS26P02383864
RPS27RPS28P25112854
RPS27RPS29P30054840
RPS27RPL27P08526836
RPS27MDM2Q00987821
RPS27RPS19P39019815
RPS27RPS25P25111806
RPS27RPS14P06366793
RPS27RPS15AP39027763
RPS27RPS24P16632759
RPS27RPL5P46777757
RPS27RPL38P23411752
RPS27RPL35P42766746
RPS27RPL26P61254742
RPS27RPL30P04645737

IntAct

184 interactions, top by confidence:

ABTypeScore
MAP3K14CHUKpsi-mi:“MI:0914”(association)0.950
CFTRESYT2psi-mi:“MI:0914”(association)0.710
NCBP2KPNA3psi-mi:“MI:0914”(association)0.640
LRRK2RPS27psi-mi:“MI:0217”(phosphorylation reaction)0.640
RACK1RPS17psi-mi:“MI:0915”(physical association)0.610
MDM2RPS27psi-mi:“MI:0407”(direct interaction)0.600
MDM2RPS27psi-mi:“MI:0915”(physical association)0.600
RPS27MDM2psi-mi:“MI:0915”(physical association)0.600
RPS27PSME3psi-mi:“MI:0915”(physical association)0.560
ENOPH1RPS27psi-mi:“MI:0915”(physical association)0.550
BLMRPS27psi-mi:“MI:0915”(physical association)0.540
BLMRPS27psi-mi:“MI:0217”(phosphorylation reaction)0.540
SYNGAP1IGF2BP3psi-mi:“MI:0914”(association)0.530
RPS18RPS2psi-mi:“MI:0914”(association)0.530
P/VIRS4psi-mi:“MI:0914”(association)0.530
PPP2R2BDDX3Xpsi-mi:“MI:0914”(association)0.460
TUBA1ATUBAL3psi-mi:“MI:0914”(association)0.420
RPS27RPS7psi-mi:“MI:0915”(physical association)0.400
RPS27SKILpsi-mi:“MI:0915”(physical association)0.370
RPS27ENTPD4psi-mi:“MI:0915”(physical association)0.370
TOM1RPS27psi-mi:“MI:0915”(physical association)0.370
ACTN4RPS27psi-mi:“MI:0915”(physical association)0.370

BioGRID (533): RPS27 (Affinity Capture-MS), RPS27 (Affinity Capture-MS), RPL10A (Co-fractionation), RPL12 (Co-fractionation), RPL18 (Co-fractionation), RPL18A (Co-fractionation), RPL27 (Co-fractionation), RPL27A (Co-fractionation), RPL30 (Co-fractionation), RPL6 (Co-fractionation), RPL7A (Co-fractionation), RPL8 (Co-fractionation), RPL9 (Co-fractionation), RPLP2 (Co-fractionation), RPS18 (Co-fractionation)

ESM2 similar proteins: A0A1D8PTI7, A0A1L8H579, A0A1W2PPG7, A1X8D9, G1TZ76, O64650, O74330, P03131, P06459, P09003, P0C567, P0DOC8, P11332, P17387, P24051, P35997, P36826, P36833, P38711, P40569, P42677, P47903, P47904, P55833, P68834, P68835, P68958, P68959, Q02271, Q13670, Q1X709, Q2KHT7, Q39072, Q3T0B7, Q5RBK1, Q5RGZ1, Q67616, Q67708, Q6DRC3, Q6ZWU9

Diamond homologs: A0A1D8PTI7, A1RRN0, A2BN94, A3MUV2, A4WLR8, B1YAF9, B6YT34, C5A6X9, G1TZ76, O64650, O74330, P24051, P35997, P38654, P38711, P42677, P47903, P47904, P55833, P58078, Q2KHT7, Q3T0B7, Q46C77, Q4J9B1, Q5JE50, Q5RBK1, Q6ZWU9, Q6ZWY3, Q71TY3, Q71UM5, Q7RVN2, Q8L953, Q8T1V4, Q8U474, Q8ZTY4, Q96564, Q973F9, Q97Z80, Q9M2F1, Q9TXP0

SIGNOR signaling

1 interactions.

AEffectBMechanism
RPS27“form complex”“40S cytosolic small ribosomal subunit”binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 190 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:

PathwayPartnersFoldFDR
Eukaryotic Translation Initiation716.5×4e-06
Cap-dependent Translation Initiation716.5×4e-06
SARS-CoV-1 modulates host translation machinery716.5×4e-06
Formation of the ternary complex, and subsequently, the 43S complex1016.4×2e-08
Nonsense-Mediated Decay (NMD)916.0×1e-07
Ribosomal scanning and start codon recognition1116.0×5e-09
TNFR1-induced NF-kappa-B signaling pathway615.4×4e-05
Eukaryotic Translation Elongation714.9×8e-06

GO biological processes:

GO termPartnersFoldFDR
non-canonical NF-kappaB signal transduction526.5×3e-04
cytoplasmic translation1517.5×7e-12
translational initiation715.8×1e-04
regulation of translational initiation514.7×3e-03
extrinsic apoptotic signaling pathway via death domain receptors512.6×5e-03
canonical NF-kappaB signal transduction511.5×6e-03
translation1711.0×1e-10
tumor necrosis factor-mediated signaling pathway510.4×9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance2
Likely benign5
Benign2

Top pathogenic / likely-pathogenic (0)

SpliceAI

236 predictions. Top by Δscore:

VariantEffectΔscore
1:153990974:GAGA:Gdonor_gain1.0000
1:153991112:TAGCT:Tacceptor_loss1.0000
1:153991113:A:AGacceptor_gain1.0000
1:153991113:A:ATacceptor_loss1.0000
1:153991114:G:GAacceptor_gain1.0000
1:153991114:GCTC:Gacceptor_gain1.0000
1:153991220:CCAGG:Cdonor_loss1.0000
1:153991223:GGT:Gdonor_loss1.0000
1:153991224:G:GAdonor_loss1.0000
1:153991225:T:Adonor_loss1.0000
1:153991672:AGAAG:Adonor_loss1.0000
1:153991673:GAAG:Gdonor_gain1.0000
1:153991673:GAAGG:Gdonor_loss1.0000
1:153991674:AAG:Adonor_loss1.0000
1:153991675:AG:Adonor_loss1.0000
1:153991676:GGTAA:Gdonor_loss1.0000
1:153991677:GT:Gdonor_loss1.0000
1:153991678:T:Gdonor_loss1.0000
1:153992064:GGAT:Gacceptor_gain1.0000
1:153990799:GCCT:Gdonor_gain0.9900
1:153990803:G:GGdonor_gain0.9900
1:153990977:A:Gdonor_gain0.9900
1:153990994:C:Gdonor_gain0.9900
1:153991010:G:Tdonor_gain0.9900
1:153991022:C:Tdonor_gain0.9900
1:153991113:AGCTC:Aacceptor_gain0.9900
1:153991114:GC:Gacceptor_gain0.9900
1:153991114:GCT:Gacceptor_gain0.9900
1:153991114:GCTCG:Gacceptor_gain0.9900
1:153991208:G:GTdonor_gain0.9900

AlphaMissense

549 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
1:153991202:T:CF32L1.000
1:153991204:C:AF32L1.000
1:153991204:C:GF32L1.000
1:153991589:T:CF47L1.000
1:153991591:T:AF47L1.000
1:153991591:T:GF47L1.000
1:153991593:G:TS48I1.000
1:153991642:C:GC64W1.000
1:153992077:G:TR80M1.000
1:153991208:G:CD34H0.999
1:153991212:T:AV35E0.999
1:153991217:T:CC37R0.999
1:153991587:T:AV46D0.999
1:153991589:T:AF47I0.999
1:153991592:A:CS48R0.999
1:153991594:C:AS48R0.999
1:153991594:C:GS48R0.999
1:153991616:T:CC56R0.999
1:153991617:G:AC56Y0.999
1:153991618:T:GC56W0.999
1:153991625:T:CC59R0.999
1:153991626:G:AC59Y0.999
1:153991627:C:GC59W0.999
1:153991638:T:AL63H0.999
1:153991640:T:CC64R0.999
1:153991641:G:AC64Y0.999
1:153991653:G:AG68E0.999
1:153991653:G:TG68V0.999
1:153991656:G:AG69E0.999
1:153991656:G:TG69V0.999

dbSNP variants (sampled 300 via entrez): RS1000118647 (1:153989524 C>T), RS1000509046 (1:153988937 T>C), RS1002259443 (1:153991943 C>G), RS1002934205 (1:153989537 C>A,G), RS1004220318 (1:153989566 G>A), RS1004996538 (1:153989901 A>G), RS1005026391 (1:153990217 C>T), RS1006248863 (1:153992454 T>TC), RS1006565022 (1:153991672 A>G,T), RS1006826721 (1:153991032 C>G,T), RS1006940689 (1:153991401 A>G), RS1008501466 (1:153990078 GTTTATTTA>G,GTTTA,GTTTATTTATTTA), RS1008602878 (1:153988838 C>T), RS1009926139 (1:153989175 G>A,C,T), RS1011570090 (1:153990290 T>C)

Disease associations

OMIM: gene MIM:603702 | disease phenotypes:

GenCC curated gene-disease

DiseaseClassificationInheritance
Diamond-Blackfan anemia 17LimitedUnknown

Mondo (1): Diamond-Blackfan anemia 17 (MONDO:0044310)

Orphanet (0):

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000047Hypospadias
HP:0000085Horseshoe kidney
HP:0000104Renal agenesis
HP:0000119Abnormality of the genitourinary system
HP:0000185Cleft soft palate
HP:0000218High palate
HP:0000234Abnormality of the head
HP:0000252Microcephaly
HP:0000286Epicanthus
HP:0000294Low anterior hairline
HP:0000316Hypertelorism
HP:0000347Micrognathia
HP:0000369Low-set ears
HP:0000431Wide nasal bridge
HP:0000465Webbed neck
HP:0000470Short neck
HP:0000486Strabismus
HP:0000508Ptosis
HP:0000519Developmental cataract
HP:0000912Sprengel anomaly
HP:0000953Hyperpigmentation of the skin
HP:0000980Pallor
HP:0001087Developmental glaucoma
HP:0001199Triphalangeal thumb
HP:0001227Abnormality of the thenar eminence
HP:0001254Lethargy
HP:0001510Growth delay
HP:0001518Small for gestational age
HP:0001627Abnormal heart morphology

GWAS associations

12 associations (top):

StudyTraitp-value
GCST010136_18Fruit consumption3.000000e-08
GCST010137_3Cooked vegetable consumption3.000000e-09
GCST010142_60Fish- and plant-related diet4.000000e-09
GCST010142_92Fish- and plant-related diet6.000000e-14
GCST010696_22Cortical thickness (min-P)4.000000e-10
GCST010697_50Cortical surface area (min-P)1.000000e-12
GCST010698_81Subcortical volume (min-P)1.000000e-23
GCST010699_7Brain morphology (min-P)1.000000e-10
GCST010700_11Cortical thickness (MOSTest)4.000000e-13
GCST010701_73Cortical surface area (MOSTest)4.000000e-09
GCST010702_45Subcortical volume (MOSTest)4.000000e-10
GCST010703_276Brain morphology (MOSTest)2.000000e-15

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0008111diet measurement
EFO:0004346neuroimaging measurement
EFO:0004840cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1932893 (SINGLE PROTEIN), CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX)

Molecules with ChEMBL bioactivity

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

MoleculeNamePhasePatents
CHEMBL6067484GENTAMICIN SULFATE4

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

ChEMBL bioactivities

59 potent at pChembl≥5 of 63 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.19IC506.4nMCHEMBL2089255
7.43IC5037nMCHEMBL2089254
6.88IC50131nMCHEMBL2089255
6.64IC50228nMCHEMBL2089253
6.52IC50300nMCHEMBL4109308
6.42IC50380nMCHEMBL4109308
6.42IC50380nMCHEMBL4574496
6.41IC50390nMCHEMBL4126894
6.39IC50410nMCHEMBL4114159
6.35IC50450nMCHEMBL4126496
6.33Kd469.7nMCHEMBL5653589
6.33ED50469.7nMCHEMBL5653589
6.30IC50500nMCHEMBL4574496
6.30IC50500nMCHEMBL4560206
6.28IC50529nMCHEMBL211195
6.25IC50568nMCHEMBL424872
6.16IC50690nMCHEMBL4130157
6.15IC50710nMCHEMBL4108338
6.11IC50780nMCHEMBL4114159
6.09IC50820nMCHEMBL4109308
6.07IC50850nMCHEMBL4107559
6.07IC50850nMCHEMBL4533299
6.05IC50900nMCHEMBL4126894
6.05IC50900nMCHEMBL4126496
6.04IC50920nMCHEMBL4554909
5.97IC501060nMCHEMBL4128388
5.89IC501290nMCHEMBL4130157
5.86IC501370nMCHEMBL4107559
5.84IC501440nMCHEMBL4108338
5.81IC501540nMCHEMBL4534859
5.76IC501730nMCHEMBL4534859
5.75IC501800nMCHEMBL2089254
5.69IC502050nMCHEMBL4566239
5.68IC502080nMCHEMBL4446635
5.66IC502210nMCHEMBL4446635
5.66EC502200nMCHEMBL4464929
5.64IC502270nMCHEMBL4533299
5.63IC502330nMCHEMBL4566239
5.62IC502380nMCHEMBL4128388
5.58IC502630nMCHEMBL4128250
5.55IC502820nMCHEMBL4127458
5.53IC502970nMCHEMBL4127311
5.51IC503080nMCHEMBL4126072
5.46IC503500nMCHEMBL4525277
5.44IC503630nMCHEMBL4469712
5.40IC503970nMCHEMBL2089252
5.39IC504100nMCHEMBL4128560
5.38IC504200nMCHEMBL210861
5.37IC504300nMCHEMBL4127016
5.36IC504380nMCHEMBL4527910

PubChem BioAssay actives

57 with measured affinity, of 229 total; 35 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-[[4-amino-6-(tert-butylamino)-5-cyano-2-pyridinyl]amino]benzamide683374: Inhibition of Mps1-mediated p38 MAPK phosphorylation after 90 mins by DELFIA assayic500.0064uM
4-[(4-amino-5-cyano-6-ethoxy-2-pyridinyl)amino]benzamide683374: Inhibition of Mps1-mediated p38 MAPK phosphorylation after 90 mins by DELFIA assayic500.0370uM
4-amino-6-anilino-2-ethoxypyridine-3-carbonitrile683374: Inhibition of Mps1-mediated p38 MAPK phosphorylation after 90 mins by DELFIA assayic500.2280uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide1585498: 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 methodic500.3000uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-3-[4-(triazolo[4,5-b]pyridin-3-yl)phenyl]propanamide1532845: 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 assayic500.3800uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide1497947: 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 assayic500.3900uM
N-(3-chloro-2-pyridinyl)-4-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide1497947: 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 assayic500.4100uM
N-(3-chloro-2-pyridinyl)-4-(5-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide1497947: 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 assayic500.4500uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149300: Binding affinity to human RPS27 incubated for 45 mins by Kinobead based pull down assaykd0.4697uM
N-(1-methylpyrrolo[2,3-c]pyridin-7-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide1532846: 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 assayic500.5000uM
4-amino-N-benzyl-5-cyano-6-ethoxypyridine-2-carboxamide683374: Inhibition of Mps1-mediated p38 MAPK phosphorylation after 90 mins by DELFIA assayic500.5290uM
4-amino-5-cyano-6-ethoxy-N-[(4-methylsulfonylphenyl)methyl]pyridine-2-carboxamide683374: Inhibition of Mps1-mediated p38 MAPK phosphorylation after 90 mins by DELFIA assayic500.5680uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylbenzamide1497947: 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 assayic500.6900uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-5-(triazolo[4,5-b]pyridin-3-yl)pyridine-2-carboxamide1497947: 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 assayic500.7100uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide1532845: 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 assayic500.8500uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide1497947: 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 assayic500.8500uM
N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylpiperidine-1-carboxamide1532846: 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 assayic500.9200uM
N-isoquinolin-1-yl-4-(1-methylpyrazol-4-yl)-N-[(3R)-piperidin-3-yl]benzamide1497947: 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 assayic501.0600uM
N-isoquinolin-1-yl-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide1532846: 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 assayic501.5400uM
N-(3-methyl-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide1532845: 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 assayic502.0500uM
N-(3-chloro-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide1532846: 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 assayic502.0800uM
N-(5,8-dihydroisoquinolin-1-yl)-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide1584424: Inhibition of human 80S ribosome-mediated PCSK9 translation expressed in CHO-K1 cells assessed as reduction in PCSK9 secretionec502.2000uM
N-isoquinolin-1-yl-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide1497947: 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 assayic502.6300uM
N-(3-chloro-2-pyridinyl)-4-(6-methylpyrazin-2-yl)-N-[(3R)-piperidin-3-yl]benzamide1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISAic502.8200uM
N-(3-chloro-2-pyridinyl)-4-[6-(dimethylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISAic502.9700uM
N-(3-chloro-2-pyridinyl)-4-[6-(methylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISAic503.0800uM
N-isoquinolin-1-yl-4-(6-methyl-1,2-benzoxazol-3-yl)-N-[(3R)-piperidin-3-yl]piperazine-1-carboxamide1532845: 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 assayic503.5000uM
N-(3-methylpyrazin-2-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide1532846: 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 assayic503.6300uM
4-amino-2-ethoxy-6-(2-phenylethylamino)pyridine-3-carbonitrile683374: Inhibition of Mps1-mediated p38 MAPK phosphorylation after 90 mins by DELFIA assayic503.9700uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-6-(triazolo[4,5-b]pyridin-3-yl)pyridine-3-carboxamide1497947: 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 assayic504.1000uM
N-(4-amino-5-cyano-6-ethoxy-2-pyridinyl)-2-phenylacetamide683374: Inhibition of Mps1-mediated p38 MAPK phosphorylation after 90 mins by DELFIA assayic504.2000uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazin-2-ylbenzamide1497947: 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 assayic504.3000uM
4-(2-fluorophenyl)-N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide1532846: 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 assayic504.3800uM
2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide;sulfuric acid717551: Inhibition of mitochondrial ribosome-mediated protein synthesis in human HeLa cells assessed as {35S]methionine incorporation by autoradiographyic507.4000uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149300: Binding affinity to human RPS27 incubated for 45 mins by Kinobead based pull down assaykd7.6532uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
bisphenol Aaffects expression, decreases expression, increases expression, affects cotreatment5
trichostatin Aaffects cotreatment, increases expression3
sodium arsenitedecreases expression, increases expression3
methylmercuric chlorideincreases expression2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression, increases expression2
bisphenol Sdecreases expression, increases expression, affects cotreatment2
Particulate Matterincreases abundance, affects cotreatment, decreases expression2
FR900359affects phosphorylation1
bisphenol Faffects cotreatment, decreases expression1
triphenyl phosphateaffects expression1
2-methyl-4-isothiazolin-3-oneincreases expression1
beta-lapachoneincreases expression1
arseniteaffects binding, increases reaction1
methylparabendecreases expression1
coumarinincreases phosphorylation1
epigallocatechin gallateincreases expression1
arsenic trichloridedecreases expression, increases abundance, affects cotreatment1
4-hydroxy-equileninincreases expression1
2,3,5-(triglutathion-S-yl)hydroquinonedecreases ADP-ribosylation1
CD 437decreases expression1
chloropicrinincreases expression1
calfactantaffects cotreatment, increases expression1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic aciddecreases expression1
N-butyrylglucosamineincreases expression1
dorsomorphinaffects cotreatment, increases expression1
jinfukangincreases expression1
LDN 193189affects cotreatment, decreases expression1
bisphenol AFincreases expression1
nabiximolsincreases expression1
Sunitinibincreases expression1

ChEMBL screening assays

97 unique, capped per target: 97 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1936525BindingInhibition of MPS15-(2-amino-pyrimidin-4-yl)-1H-pyrrole and 2-(2-amino-pyrimidin-4-yl)-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one derivatives as new classes of selective and orally available Polo-like kinase 1 inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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