RNASEL

gene
On this page

Summary

RNASEL (ribonuclease L, HGNC:10050) is a protein-coding gene on chromosome 1q25.3, encoding 2-5A-dependent ribonuclease (Q05823). Endoribonuclease that functions in the interferon (IFN) antiviral response.

This gene encodes a component of the interferon-regulated 2-5A system that functions in the antiviral and antiproliferative roles of interferons. The protein is involved in innate immunity and is active against multiple RNA viruses, including the influenza and SARS-CoV-2 viruses. Mutations in this gene have been associated with predisposition to prostate cancer and this gene is a candidate for the hereditary prostate cancer 1 (HPC1) allele.

Source: NCBI Gene 6041 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): multisystem inflammatory syndrome in children and adults (Moderate, GenCC) — +1 more curated relationship
  • GWAS associations: 2
  • Clinical variants (ClinVar): 169 total — 1 pathogenic, 2 likely-pathogenic
  • Phenotypes (HPO): 3
  • Druggable target: yes
  • MANE Select transcript: NM_021133

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:10050
Approved symbolRNASEL
Nameribonuclease L
Location1q25.3
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000135828
Ensembl biotypeprotein_coding
OMIM180435
Entrez6041

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000367559, ENST00000539397, ENST00000890859, ENST00000946546

RefSeq mRNA: 1 — MANE Select: NM_021133 NM_021133

CCDS: CCDS1347

Canonical transcript exons

ENST00000367559 — 7 exons

ExonStartEnd
ENSE00000922066182584081182584166
ENSE00001445028182585327182586970
ENSE00001445029182589167182589256
ENSE00001818322182573634182575578
ENSE00002328872182582053182582258
ENSE00002350700182581225182581357
ENSE00002416678182576256182576389

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 90.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.9815 / max 88.6392, expressed in 1427 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
161583.74301302
161570.7507390
161590.4565266
161560.031313

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
amniotic fluidUBERON:000017390.81gold quality
palpebral conjunctivaUBERON:000181287.85gold quality
germinal epithelium of ovaryUBERON:000130486.15gold quality
epithelium of nasopharynxUBERON:000195186.02gold quality
bloodUBERON:000017885.78gold quality
esophagus squamous epitheliumUBERON:000692084.49gold quality
visceral pleuraUBERON:000240183.58gold quality
mucosa of paranasal sinusUBERON:000503083.55gold quality
jejunal mucosaUBERON:000039983.52gold quality
parietal pleuraUBERON:000240083.30gold quality
bronchial epithelial cellCL:000232882.94gold quality
seminal vesicleUBERON:000099882.91gold quality
corpus epididymisUBERON:000435982.90gold quality
monocyteCL:000057682.82gold quality
leukocyteCL:000073882.81gold quality
tibiaUBERON:000097982.78gold quality
mononuclear cellCL:000084282.64gold quality
pleuraUBERON:000097782.42gold quality
caput epididymisUBERON:000435881.76gold quality
granulocyteCL:000009481.47gold quality
calcaneal tendonUBERON:000370181.44gold quality
epithelium of esophagusUBERON:000197681.17gold quality
adrenal tissueUBERON:001830380.83gold quality
colonic mucosaUBERON:000031780.81gold quality
rectumUBERON:000105280.30gold quality
tendonUBERON:000004379.66gold quality
mucosa of transverse colonUBERON:000499179.65gold quality
epithelium of bronchusUBERON:000203179.58gold quality
oral cavityUBERON:000016779.57gold quality
stromal cell of endometriumCL:000225579.30gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes4.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BRCA1, MYC

miRNA regulators (miRDB)

100 targeting RNASEL, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3163100.0077.238605
HSA-MIR-29A-3P100.0073.111835
HSA-MIR-29B-3P100.0073.181833
HSA-MIR-29C-3P100.0073.151833
HSA-MIR-4533100.0069.482758
HSA-MIR-126-5P100.0072.713180
HSA-MIR-450A-1-3P100.0069.331837
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-200B-3P100.0073.312693
HSA-MIR-200C-3P100.0073.352685
HSA-MIR-429100.0073.442698
HSA-MIR-34A-5P99.9971.211784
HSA-MIR-449A99.9971.051776
HSA-MIR-103A-3P99.9869.141595
HSA-MIR-10799.9869.141595
HSA-MIR-34C-5P99.9770.451577
HSA-MIR-449B-5P99.9770.261580
HSA-MIR-3688-3P99.9772.022834
HSA-MIR-314899.9775.066478
HSA-MIR-302E99.9670.742669
HSA-MIR-548AT-5P99.9670.832666
HSA-MIR-1468-3P99.9672.743797
HSA-MIR-545-3P99.9570.742783
HSA-MIR-185-3P99.9567.011743
HSA-MIR-498-3P99.9171.271114
HSA-MIR-106A-5P99.9073.942683
HSA-MIR-990299.8969.152250
HSA-MIR-568299.8972.561005
HSA-MIR-17-5P99.8973.832665
HSA-MIR-302A-3P99.8971.231777

Literature-anchored findings (GeneRIF, showing 40)

  • Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in patients and families with prostate cancer. (PMID:11941539)
  • Analysis of the RNASEL gene in familial and sporadic prostate cancer. A total of six variants were identified, including one intronic and five exonic changes (three missense and two silent alterations). (PMID:12022038)
  • Structural and functional features of the 37-kDa 2-5A-dependent RNase L in chronic fatigue syndrome (PMID:12034027)
  • physical performance and prediction of 2-5A synthetase antiviral pathway activity in patients with chronic fatigue syndrome. (PMID:12073768)
  • in rRNA and small nucleolar RNA maturation, not in telomere elongation inhibition (PMID:12118002)
  • A novel founder mutation in the RNASEL gene, 471delAAAG, is associated with prostate cancer in Ashkenazi Jews. (PMID:12145743)
  • The variant Arg462Gln has 3X less enzymatic activity than the wildtype and is significantly associated with prostate cancer risk (P=0.007). (PMID:12415269)
  • Author reviews the tumor suppressor role of RNase L, proposing that it functions in counteracting prostate cancer by virtue of its ability to degrade RNA, thus initiating a cellular stress response that leads to apoptosis. (PMID:12590567)
  • A genome-wide scan of high risk prostate cancer families in North America has demonstrated linkage of a particular marker to chromosme 1q(HPC1). (PMID:12653398)
  • polymorphic changes within the RNASEL gene may be associated with familial prostate cancer risk (PMID:12915880)
  • JNK and RNase L function in an integrated signaling pathway during the IFN response that leads to elimination of virus-infected cells through apoptosis (PMID:14570908)
  • RNASEL may function as a tumor suppressor in prostate cancer. (PMID:14695991)
  • does not constitute a major cell defence mechanism against the varicella-zoster virus infection (PMID:15107989)
  • Studies report an association between the RNASEL G1385A variant and prostate cancer risk; this variant does not appear to be implicated in the development of breast cancer. (PMID:15330212)
  • RNASEL does not have a major role in prostate cancer etiology (PMID:15534086)
  • These results indicated that the ankyrin-repeat domain of RNase L constricts its structure by binding of 2-5A. This observation suggests a revised model of the 2-5A-induced activation of RNase L. (PMID:15849753)
  • Human translation termination factor eRF3/GSPT1 is an interacting partner of RNase L. (PMID:15908960)
  • results suggest that RNASEL variants Glu265X and Arg462Gln may contribute to the tumorigenesis of sporadic and familial pancreatic cancer (PMID:15981205)
  • Single nucleotide polymorphisms associated with hereditary prostate cancer. (PMID:16114055)
  • Hepatitis c virus polyprotein expression caused a severe cytopathological effect in human cells as a result of inhibition of protein synthesis and apoptosis induction, triggered by the activation of the IFN-induced enzymes PKR and RNase L systems. (PMID:16156900)
  • androgen receptor and the interferon-activated RNase L interact with each other in a ligand-dependent manner (PMID:16166078)
  • 2’-5’-linked oligoadenylate activation of RNase L produces a remarkable stimulation of transcription (>/=20-fold) for genes that suppress virus replication and prostate cancer. (PMID:16203993)
  • characterization of 2’,5’-linked oligoadenylate binding determinant of human RNase L (PMID:16234235)
  • single nucleotide polymorphisms (SNPs) identified in RNASEL exons in hospitalized patients with West Nile Virus infection (PMID:16235172)
  • RNASEL genetic alterations does not support a significant role in prostate cancer predisposition in Israeli Ashkenazi Jews. (PMID:16537704)
  • Data suggest that the primary role of double-stranded RNA binding by the NS1A protein in virus-infected cells is to sequester dsRNA away from RNAse L. (PMID:16627618)
  • Gene is associated with inherited prostatic cancer. [review] (PMID:16869093)
  • A silent polymorphism in the RNASEL gene occurs more prevalently in high-risk Ashkenazi breast/ovarian cancer patients without a BRCA1/2 mutation. (PMID:16944274)
  • Compared with the genotype Asp/Asp, the Glu variant at the Asp541Glu polymorphism increases prostate cancer risk by <2-fold in Caucasians, regardless of family history of the disease. (PMID:17020975)
  • Report of the crystal structure of the N-terminal ankyrin repeat domain of human RNase L complexed with an activator molecule containing a 5’-phosphorylated 2’,5’-linked oligoadenylate, [(pp)p(A2’p5’)(n)A]. (PMID:17150764)
  • the IFN-inducible RNase L may play an important role during stress-response through RNA-degradation and apoptosis (PMID:17200614)
  • study indicated only p53 & RNASEL genotypes had significant influence on age of onset of Lynch syndrome in an additive mode of inheritance & that effects of both variants are purely additive supporting the notion (PMID:17224235)
  • Positive association between higher trans-fatty acid consumption and prostate cancer may be modified by the functional RNASEL variant R462Q. (PMID:17234723)
  • HuR-dependent regulation of RNase-L enhances its antiviral activity, demonstrating the functional significance of this regulation (PMID:17237228)
  • the effects of oligo A synthetase/RNase on the replication cycle of parainfluenza virus type 5 (PMID:17307214)
  • RNase L could have a role in cancer biology and evidence of a tumor suppressor function of RNase L has emerged from studies on the genetics of hereditary prostate cancer [review] (PMID:17400356)
  • results suggest that the RNASEL Gln/Gln genotype does not play an important role in the etiology of prostate cancer in the general population (PMID:17407163)
  • RNASEL has a role as a predisposition gene for prostate cancer in African Americans and Hispanic Caucasians (PMID:17908993)
  • common variation in the putative prostate cancer susceptibility gene, RNASEL, or its inhibitor does not contribute significantly to prostate cancer risk in Tobago Afro-Caribbean population (PMID:18189233)
  • This prospective study suggests that prostate cancer in patients with the R462Q allelic variant of the HPC1/RNASEL gene is not associated with more aggressive clinical or pathological features in radical prostatectomy specimens. (PMID:18289577)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusRnaselENSMUSG00000066800
rattus_norvegicusRnaselENSRNOG00000027017

Protein

Protein identifiers

2-5A-dependent ribonucleaseQ05823 (reviewed: Q05823)

Alternative names: Ribonuclease 4, Ribonuclease L

All UniProt accessions (1): Q05823

UniProt curated annotations — full annotation on UniProt →

Function. Endoribonuclease that functions in the interferon (IFN) antiviral response. In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress-response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. In the crosstalk between autophagy and apoptosis proposed to induce autophagy as an early stress response to small double-stranded RNA and at later stages of prolonged stress to activate caspase-dependent proteolytic cleavage of BECN1 to terminate autophagy and promote apoptosis. Might play a central role in the regulation of mRNA turnover. Cleaves 3’ of UpNp dimers, with preference for UU and UA sequences, to sets of discrete products ranging from between 4 and 22 nucleotides in length. Involved in intercellular immune signaling. Cross-activated by 2’,5’-oligoadenylates (2-5A) previously generated in RNA virus-infected cells, triggers type I interferon signaling in uninfected neighboring cells to limit local spread of infection.

Subunit / interactions. Monomer (inactive form) or homodimer. Interacts with ABCE1; this interaction inhibits the RNASEL.

Subcellular location. Cytoplasm. Mitochondrion.

Tissue specificity. Highly expressed in spleen and thymus followed by prostate, testis, uterus, small intestine, colon and peripheral blood leukocytes.

Disease relevance. Prostate cancer, hereditary, 1 (HPC1) [MIM:601518] A condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. After binding to 2-5A (5’-phosphorylated 2’,5’-linked oligoadenylates) the homodimerization and subsequent activation occurs. Inhibited by RNASEL inhibitor ABCE1/RLI, a cytoplasmic member of the ATP-binding cassette (ABC) transporter family.

Cofactor. Manganese or magnesium. Required for optimal RNA cleavage rates.

Domain organisation. The nine ankyrin repeats also called 2-5A sensor constitute the N-terminus 2-5A binding domain. The protein kinase domain is predicted to be catalytically inactive. It allows the homodimerization. The ribonuclease domain is located in the C-terminus. A single active nuclease domain in a dimer is sufficient for ribonuclease activity.

Induction. By interferons. Virus replication in higher vertebrates is restrained by IFNs that cause cells to transcribe genes encoding antiviral proteins, such as 2’-5’ oligoadenylate synthetases (OASs). oligoadenylate synthetase is stimulated by dsRNA to produce 5’-phosphorylated, 2’-5’-linked oligoadenylates (2-5A), whose function is to activate RNASEL.

Similarity. Belongs to the protein kinase superfamily.

Isoforms (2)

UniProt IDNamesCanonical?
Q05823-11yes
Q05823-22

RefSeq proteins (1): NP_066956* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR002110Ankyrin_rptRepeat
IPR010513KEN_domDomain
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR036770Ankyrin_rpt-contain_sfHomologous_superfamily
IPR038357KEN_sfHomologous_superfamily
IPR042745RNase-L_RNaseDomain

Pfam: PF00069, PF06479, PF12796, PF13857

Enzyme classification (BRENDA):

  • EC 4.6.1.19 — ribonuclease T2 (BRENDA: 54 organisms, 147 substrates, 64 inhibitors, 73 Km, 16 kcat entries)

Substrate kinetics (BRENDA)

30 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
CPU0.076–2011
APG0.003–1.144
APA0.005–0.0653
APC0.025–0.133
APU0.03–0.0783
CPG0.11–2.153
GPA0.02–0.0723
GPC0.107–0.113
GPG0.044–0.713
GPU0.075–0.123
UPA0.05–0.1443
UPG0.06–0.693
UPU0.113–0.223
2’,3’-CCMP0.16–0.42
2’,3’-CUMP0.43–6.12

UniProt features (97 total): helix 43, strand 12, repeat 9, mutagenesis site 9, sequence variant 7, turn 5, region of interest 4, domain 2, splice variant 2, chain 1, zinc finger region 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDBMethodResolution (Å)
1WDYX-RAY DIFFRACTION1.8
4OAVX-RAY DIFFRACTION2.1
4G8KX-RAY DIFFRACTION2.4
4OAUX-RAY DIFFRACTION2.6
4G8LX-RAY DIFFRACTION2.8

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q05823-F191.960.83

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 (1): 684

Mutagenesis-validated functional residues (9):

PositionPhenotype
240reduced 2-5a binding activity; almost complete loss of 2-5a binding activity; when associated with n-274.
274reduced 2-5a binding activity; almost complete loss of 2-5a binding activity; when associated with n-240.
392complete loss of enzymatic activity and enzyme dimerization. no change in binding to 2-5a and rna.
583no change in enzymatic activity.
584no change in enzymatic activity.
632no change in enzymatic activity.
661complete loss of enzymatic activity.
667complete loss of enzymatic activity. no change in 2-5a binding and enzyme dimerization.
672complete loss of enzymatic activity. no change in 2-5a binding activity and enzyme dimerization.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

IDPathway
R-HSA-8983711OAS antiviral response
R-HSA-909733Interferon alpha/beta signaling
R-HSA-1169410Antimicrobial mechanism of IFN-stimulated genes
R-HSA-1280215Cytokine Signaling in Immune system
R-HSA-168256Immune System
R-HSA-913531Interferon Signaling

MSigDB gene sets: 221 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_CARBOHYDRATE_TRANSPORT, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, MODULE_255, GOMF_NUCLEASE_ACTIVITY, MODULE_64, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_317, TAKADA_GASTRIC_CANCER_COPY_NUMBER_DN, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (12): rRNA processing (GO:0006364), RNA processing (GO:0006396), mRNA processing (GO:0006397), protein phosphorylation (GO:0006468), regulation of mRNA stability (GO:0043488), negative regulation of viral genome replication (GO:0045071), fat cell differentiation (GO:0045444), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of D-glucose import across plasma membrane (GO:0046326), defense response to virus (GO:0051607), regulation of gene expression (GO:0010468), regulation of RNA metabolic process (GO:0051252)

GO Molecular Function (15): RNA binding (GO:0003723), RNA endonuclease activity (GO:0004521), RNA nuclease activity (GO:0004540), protein kinase activity (GO:0004672), ATP binding (GO:0005524), zinc ion binding (GO:0008270), hydrolase activity (GO:0016787), rRNA binding (GO:0019843), identical protein binding (GO:0042802), ribonucleoprotein complex binding (GO:0043021), nucleotide binding (GO:0000166), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): mitochondrial matrix (GO:0005759), cytosol (GO:0005829), nuclear matrix (GO:0016363), cytoplasm (GO:0005737), mitochondrion (GO:0005739)

Reactome top-level categories

Rollup of top-4 pathways:

CategoryPathways
Interferon Signaling2
Antimicrobial mechanism of IFN-stimulated genes1
Immune System1
Cytokine Signaling in Immune system1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
RNA processing2
gene expression2
nuclease activity2
cytoplasm2
rRNA metabolic process1
ribosome biogenesis1
RNA biosynthetic process1
primary metabolic process1
mRNA metabolic process1
phosphorylation1
protein modification process1
regulation of RNA stability1
regulation of mRNA catabolic process1
viral genome replication1
regulation of viral genome replication1
negative regulation of viral process1
cell differentiation1
regulation of transcription by RNA polymerase II1
transcription by RNA polymerase II1
positive regulation of DNA-templated transcription1
positive regulation of D-glucose transmembrane transport1
regulation of D-glucose import across plasma membrane1
D-glucose import across plasma membrane1
defense response1
response to virus1
regulation of macromolecule biosynthetic process1
RNA metabolic process1
regulation of nucleobase-containing compound metabolic process1
regulation of macromolecule metabolic process1
nucleic acid binding1
endonuclease activity1
RNA nuclease activity1
catalytic activity, acting on RNA1
kinase activity1
phosphotransferase activity, alcohol group as acceptor1
catalytic activity, acting on a protein1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
transition metal ion binding1

Protein interactions and networks

STRING

6792 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
RNASELOAS1P00973924
RNASELABCE1P61221918
RNASELOASLQ15646915
RNASELOAS3Q9Y6K5908
RNASELEIF2AK2P19525902
RNASELOAS2P29728859
RNASELRIGIO95786835
RNASELIFIH1Q9BYX4809
RNASELELAC2Q9BQ52759
RNASELANGP03950740
RNASELPDE12Q6L8Q7718
RNASELIFNB1P01574705
RNASELIFNAR2P48551693
RNASELMTIF2P46199688
RNASELMX1P20591688

IntAct

45 interactions, top by confidence:

ABTypeScore
HIF1ANAPBA3psi-mi:“MI:0914”(association)0.850
HIF1ANGMDSpsi-mi:“MI:0914”(association)0.640
LPAR4POTEFpsi-mi:“MI:0914”(association)0.530
SLC15A1METTL15psi-mi:“MI:0914”(association)0.530
IL13RA2METTL15psi-mi:“MI:0914”(association)0.530
SYPAPBB1psi-mi:“MI:0914”(association)0.530
RNASELIQGAP1psi-mi:“MI:0914”(association)0.500
RNASELIQGAP1psi-mi:“MI:0915”(physical association)0.500
TP53MDM2psi-mi:“MI:0914”(association)0.350
HIF1ANCNOT1psi-mi:“MI:0914”(association)0.350
ST8SIA4NRP1psi-mi:“MI:0914”(association)0.350
SYPAPBB1psi-mi:“MI:0914”(association)0.350
DOCK5DPYSL4psi-mi:“MI:0914”(association)0.350
SLC37A3CYB5R3psi-mi:“MI:0914”(association)0.350
HIF1ANST13psi-mi:“MI:0914”(association)0.350
Mpsi-mi:“MI:0914”(association)0.350
RNASELUNC119Bpsi-mi:“MI:0914”(association)0.350
ATG16L1ESYT2psi-mi:“MI:0914”(association)0.350
SV2AILVBLpsi-mi:“MI:0914”(association)0.350
S100A2PLEKHG3psi-mi:“MI:0914”(association)0.350
ST8SIA4FAM234Bpsi-mi:“MI:0914”(association)0.350
PTH2RMETTL15psi-mi:“MI:0914”(association)0.350
PRKYMETTL15psi-mi:“MI:0914”(association)0.350
SLC18A2UBXN8psi-mi:“MI:0914”(association)0.350
HNRNPCL2SMCHD1psi-mi:“MI:0914”(association)0.350

BioGRID (52): TCF12 (Two-hybrid), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-RNA), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-MS), RNASEL (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GXY4, A4IIK1, A6NGH8, B0R160, C6FG12, E7F654, O12990, O19064, O60674, O62471, P32019, Q05823, Q09178, Q1EHT7, Q1L8H0, Q20CR4, Q2T9W8, Q32KX5, Q38SD2, Q3TX51, Q3UHC2, Q3UV48, Q3V1N1, Q4VSN2, Q4VSN5, Q5RB23, Q5XUN4, Q62120, Q62689, Q641X1, Q6GLE8, Q6GM71, Q6X9E4, Q6XUX3, Q75R65, Q7KLI1, Q86V97, Q86X40, Q8BWR4, Q8C4V4

Diamond homologs: A0A072VIM5, A0A0K0PU92, A2CIR7, B9DHT4, C9JJ37, E7BQV0, G3LSH3, G8GTN7, Q05823, Q0JJ01, Q2HW56, Q2QXZ2, Q2RAQ5, Q5D0W8, Q5ICL9, Q5XIU1, Q75HA6, Q8L746, Q96BM1, Q96DX5, Q99LJ2, Q9FDY4, Q9M1I7, Q9SZI3, Q9ZVC2, S4VGD0, Q5R4S6, Q8R179, Q9N010, Q9NVX7, A0M8T3, A1X154, A4D7T3, C9JTQ0, Q00PJ3, Q05921, Q07DV3, Q07DX6, Q07DY6, Q07DZ7

SIGNOR signaling

1 interactions.

AEffectBMechanism
BRCA1“up-regulates quantity by expression”RNASEL“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic1
Likely pathogenic2
Uncertain significance136
Likely benign12
Benign8

Top pathogenic / likely-pathogenic (3)

Variant IDHGVSClassification
13005NM_021133.4(RNASEL):c.3G>A (p.Met1Ile)Pathogenic
2445339NM_021133.4(RNASEL):c.1115C>A (p.Ala372Asp)Likely pathogenic
2445376NM_021133.4(RNASEL):c.1469A>G (p.Asn490Ser)Likely pathogenic

SpliceAI

1112 predictions. Top by Δscore:

VariantEffectΔscore
1:182576251:CTTA:Cdonor_gain1.0000
1:182576254:A:ACdonor_gain1.0000
1:182576254:ACTTT:Adonor_loss1.0000
1:182576255:C:CAdonor_gain1.0000
1:182576255:CT:Cdonor_gain1.0000
1:182576255:CTT:Cdonor_gain1.0000
1:182576255:CTTT:Cdonor_gain1.0000
1:182576255:CTTTT:Cdonor_gain1.0000
1:182576385:TTAAT:Tacceptor_gain1.0000
1:182576386:TAAT:Tacceptor_gain1.0000
1:182576386:TAATC:Tacceptor_loss1.0000
1:182576387:AAT:Aacceptor_gain1.0000
1:182576387:AATC:Aacceptor_loss1.0000
1:182576388:AT:Aacceptor_gain1.0000
1:182576389:TCT:Tacceptor_loss1.0000
1:182576390:C:CCacceptor_gain1.0000
1:182576390:CTAA:Cacceptor_loss1.0000
1:182582052:CCT:Cdonor_gain1.0000
1:182582256:GTCC:Gacceptor_loss1.0000
1:182582257:TCCT:Tacceptor_loss1.0000
1:182576391:T:Aacceptor_loss0.9900
1:182579772:T:Adonor_gain0.9900
1:182582048:CTTA:Cdonor_loss0.9900
1:182582049:TTA:Tdonor_loss0.9900
1:182582050:TA:Tdonor_loss0.9900
1:182582051:A:ACdonor_gain0.9900
1:182582052:C:CCdonor_gain0.9900
1:182582052:C:CTdonor_loss0.9900
1:182582052:CCTCT:Cdonor_gain0.9900
1:182582255:GGTC:Gacceptor_gain0.9900

AlphaMissense

4931 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
1:182586429:G:CF126L0.985
1:182586429:G:TF126L0.985
1:182586431:A:GF126L0.985
1:182581236:A:GW632R0.983
1:182581236:A:TW632R0.983
1:182576295:C:GR667P0.979
1:182582140:A:GL562P0.970
1:182586611:C:GA66P0.970
1:182581234:C:AW632C0.969
1:182581234:C:GW632C0.969
1:182585631:C:AK392N0.965
1:182585631:C:GK392N0.965
1:182586413:C:GA132P0.965
1:182582245:A:GL527P0.964
1:182585639:C:GA390P0.962
1:182576310:A:GL662P0.961
1:182575530:A:CF696L0.958
1:182575530:A:TF696L0.958
1:182575532:A:GF696L0.958
1:182581243:A:CF629L0.957
1:182581243:A:TF629L0.957
1:182581245:A:GF629L0.957
1:182585625:G:CF394L0.956
1:182585625:G:TF394L0.956
1:182585627:A:GF394L0.956
1:182586424:G:TA128D0.956
1:182575522:A:GL699P0.955
1:182582066:A:GW587R0.955
1:182582066:A:TW587R0.955
1:182586629:A:GW60R0.955

dbSNP variants (sampled 300 via entrez): RS1000067288 (1:182589895 A>G), RS1000125889 (1:182574262 C>T), RS1000280983 (1:182590620 C>T), RS1000336757 (1:182590119 C>A,T), RS1000377925 (1:182581723 A>C,G,T), RS1000396228 (1:182582993 A>T), RS1000428041 (1:182576827 G>A,T), RS1000707032 (1:182585252 T>C), RS1000800351 (1:182576976 A>C), RS1000943502 (1:182588679 C>A), RS1001398265 (1:182573965 T>C), RS1001477950 (1:182588391 T>C), RS1001519295 (1:182579515 G>A,C,T), RS1001742513 (1:182577367 A>G), RS1001870470 (1:182573586 C>T)

Disease associations

OMIM: gene MIM:180435 | disease phenotypes: MIM:601518, MIM:167000

GenCC curated gene-disease

DiseaseClassificationInheritance
multisystem inflammatory syndrome in children and adultsModerateAutosomal recessive
prostate cancer, hereditary, 1LimitedAutosomal dominant

Mondo (4): prostate cancer (MONDO:0008315), prostate cancer, hereditary, 1 (MONDO:0011098), ovarian cancer (MONDO:0008170), multisystem inflammatory syndrome in children and adults (MONDO:0035375)

Orphanet (2): Familial prostate cancer (Orphanet:1331), Rare ovarian cancer (Orphanet:213500)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0003581Adult onset
HP:0012125Prostate cancer

GWAS associations

2 associations (top):

StudyTraitp-value
GCST001860_11Multiple sclerosis6.000000e-09
GCST003429_2Morning vs. evening chronotype7.000000e-18

MeSH disease descriptors (2)

DescriptorNameTree numbers
D010051Ovarian NeoplasmsC04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D011471Prostatic NeoplasmsC04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3575 (SINGLE PROTEIN)

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

ChEMBL bioactivities

61 potent at pChembl≥5 of 81 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.40Kd0.04nMCHEMBL404038
9.89EC500.13nMCHEMBL402676
9.82EC500.15nMCHEMBL414948
9.70EC500.2nMCHEMBL414948
9.70EC500.2nMCHEMBL402676
9.68EC500.21nMCHEMBL414948
9.66Kd0.22nMCHEMBL404038
9.62EC500.24nMCHEMBL214603
9.52EC500.3nMCHEMBL214603
9.35EC500.45nMCHEMBL3817920
9.30EC500.5nMCHEMBL404038
9.17EC500.68nMCHEMBL405496
9.15EC500.7nMCHEMBL384725
9.14IC500.72nMCHEMBL214603
9.10EC500.8nMCHEMBL405496
9.08EC500.84nMCHEMBL384725
8.96IC501.1nMCHEMBL414948
8.64EC502.3nMCHEMBL601938
8.62EC502.4nMCHEMBL3818262
8.60EC502.5nMCHEMBL601938
8.60EC502.5nMCHEMBL591446
8.59IC502.6nMCHEMBL402676
8.57EC502.7nMCHEMBL3819183
8.40EC504nMCHEMBL410213
8.38EC504.2nMCHEMBL2058766
8.34EC504.6nMCHEMBL410213
8.21EC506.1nMCHEMBL2414867
8.19EC506.5nMCHEMBL2058765
8.14IC507.3nMCHEMBL414948
8.01EC509.7nMCHEMBL601940
7.89EC5012.9nMCHEMBL601940
7.89IC5013nMCHEMBL414948
7.82EC5015nMCHEMBL2058764
7.80EC5016nMCHEMBL407239
7.77EC5017nMCHEMBL601940
7.72EC5019.1nMCHEMBL2414866
7.70IC5020nMCHEMBL414948
7.69EC5020.3nMCHEMBL3818726
7.62IC5024nMCHEMBL405496
7.52EC5030nMCHEMBL407239
7.28EC5053nMCHEMBL2057900
7.24IC5057nMCHEMBL384725
7.08EC5084nMCHEMBL3819262
6.98IC50105nMCHEMBL410213
6.87EC50134nMCHEMBL3818137
6.70EC50200nMCHEMBL2058187
6.68IC50210nMCHEMBL1159914
6.62EC50241nMCHEMBL2414865
6.52EC50300nMCHEMBL2058191
6.52EC50300nMCHEMBL2057902

PubChem BioAssay actives

60 with measured affinity, of 242 total; 33 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate319035: Binding affinity to human recombinant RNase Lkd<0.0001uM
[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methyl [(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] hydrogen phosphate197821: Activation of purified recombinant human Ribonuclease L by the compound was measured as degradation of poly (U) 3’[32P]p5’C3’pec500.0001uM
[(2R,3R,4R,5R)-4-[[(2R,3S,4R,5R)-5-(6-amino-2-methylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methyl [(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] hydrogen phosphate197821: Activation of purified recombinant human Ribonuclease L by the compound was measured as degradation of poly (U) 3’[32P]p5’C3’pec500.0001uM
[[(2R,3R,4R,5R)-4-[[(2R,3R,4R,5R)-4-[[(2R,3S,4R,5R)-5-(6-amino-2-methylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate197821: Activation of purified recombinant human Ribonuclease L by the compound was measured as degradation of poly (U) 3’[32P]p5’C3’pec500.0002uM
[(2R,3R,4R,5R)-4-[[(2R,3R,4R,5R)-4-[[(2R,3S,4R,5R)-5-(6-amino-8-methylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methyl [(2R,3R,4R,5R)-2-(5-fluoro-2,4-dioxopyrimidin-1-yl)-4-hydroxy-5-methyloxolan-3-yl] hydrogen phosphate1309499: Induction of recombinant human RNase L activity expressed in Escherichia coli using F-5’-r(C11U2C7)-3’ as substrate by polyacrylamide gel electrophoresisec500.0004uM
[[(2R,3R,4R,5R)-5-(6-amino-2-methylpurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate197821: Activation of purified recombinant human Ribonuclease L by the compound was measured as degradation of poly (U) 3’[32P]p5’C3’pec500.0007uM
[(2R,3R,4R,5R)-2-(6-amino-2-methylpurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] [(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methyl hydrogen phosphate197820: Activation of purified recombinant human Ribonuclease L by the compound was measured as degradation of [32P]-pC11U2C7ec500.0007uM
[(2R,3R,4R,5R)-4-[[(2R,3R,4R,5R)-4-[[(2R,3S,4R,5R)-5-(6-amino-8-methylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methyl [(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate1309499: Induction of recombinant human RNase L activity expressed in Escherichia coli using F-5’-r(C11U2C7)-3’ as substrate by polyacrylamide gel electrophoresisec500.0023uM
[(2R,3R,4R,5R)-4-[[(2R,3R,4R,5R)-4-[[(2R,3S,4R,5R)-5-(6-amino-8-methylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methyl [(2R,3R,4R,5R)-2-(2,4-dioxopyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate1309499: Induction of recombinant human RNase L activity expressed in Escherichia coli using F-5’-r(C11U2C7)-3’ as substrate by polyacrylamide gel electrophoresisec500.0024uM
[(2R,3R,4R,5R)-4-[[(2R,3R,4R,5R)-4-[[(2R,3S,4R,5R)-5-(6-amino-8-methylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methyl [(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] hydrogen phosphate457411: Inhibition of human RNaseL ANK domain expressed in Escherichia coli assessed as 5’ flurescein-r(C11U2C7)-3’ RNA cleavageec500.0025uM
[(2R,3R,4R,5R)-4-[[(2R,3R,4R,5R)-4-[[(2R,3S,4R,5R)-5-(6-amino-8-methylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methyl [(2R,3R,4R,5R)-2-(2,4-dioxopyrimidin-1-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] hydrogen phosphate1309499: Induction of recombinant human RNase L activity expressed in Escherichia coli using F-5’-r(C11U2C7)-3’ as substrate by polyacrylamide gel electrophoresisec500.0027uM
[[(2R,3R,4R,5R)-5-(6-amino-2-methylpurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-amino-2-methylpurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-amino-2-methylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate197820: Activation of purified recombinant human Ribonuclease L by the compound was measured as degradation of [32P]-pC11U2C7ec500.0040uM
[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxy-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxymethyl]phosphinic acid671695: Activation of human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-rC11-UU-C7-BHQ2 as substrate by FRET assayec500.0042uM
[[(2R,3R,4R,5R)-5-(6-aminopurin-7-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-7-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-7-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-7-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate763856: Activation of human recombinant RNase L endonuclease activity using 6-FAM-UUA UCA AAU UCU UAU UUG CCC CAU UUU UUU GGU UUA-BHQ-1 as substrate assessed as substrate cleavage measured for 50 mins by FRET assayec500.0061uM
[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxy-[[(2R,3S,4S,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxymethyl]phosphinic acid671695: Activation of human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-rC11-UU-C7-BHQ2 as substrate by FRET assayec500.0065uM
[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methyl [(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] hydrogen phosphate457411: Inhibition of human RNaseL ANK domain expressed in Escherichia coli assessed as 5’ flurescein-r(C11U2C7)-3’ RNA cleavageec500.0097uM
[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxy-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxymethyl]phosphinic acid671695: Activation of human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-rC11-UU-C7-BHQ2 as substrate by FRET assayec500.0150uM
[(2R,3R,4R,5R)-5-(6-amino-2-methylpurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-amino-2-methylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methyl [(2R,3R,4R,5R)-2-(6-amino-2-methylpurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] hydrogen phosphate197821: Activation of purified recombinant human Ribonuclease L by the compound was measured as degradation of poly (U) 3’[32P]p5’C3’pec500.0160uM
[(2R,3S,4R,5R)-5-(6-aminopurin-7-yl)-2-[[[(2R,3R,4R,5R)-2-(6-aminopurin-7-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-7-yl)-4-(2,2-dimethylpropanoyloxymethoxy)-5-[[hydroxy-[hydroxy(phosphonooxy)phosphoryl]oxyphosphoryl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-(2,2-dimethylpropanoyloxymethoxy)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxymethyl 2,2-dimethylpropanoate763856: Activation of human recombinant RNase L endonuclease activity using 6-FAM-UUA UCA AAU UCU UAU UUG CCC CAU UUU UUU GGU UUA-BHQ-1 as substrate assessed as substrate cleavage measured for 50 mins by FRET assayec500.0191uM
[(2R,3R,4R,5R)-4-[[(2R,3R,4R,5R)-4-[[(2R,3S,4R,5R)-5-(6-amino-8-methylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methyl [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate1309499: Induction of recombinant human RNase L activity expressed in Escherichia coli using F-5’-r(C11U2C7)-3’ as substrate by polyacrylamide gel electrophoresisec500.0203uM
[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxymethylphosphonic acid671695: Activation of human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-rC11-UU-C7-BHQ2 as substrate by FRET assayec500.0530uM
[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methyl [(2R,3R,4R,5R)-2-(2,4-dioxopyrimidin-1-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] hydrogen phosphate1309499: Induction of recombinant human RNase L activity expressed in Escherichia coli using F-5’-r(C11U2C7)-3’ as substrate by polyacrylamide gel electrophoresisec500.0840uM
[(2R,3R,4R,5R)-4-[[(2R,3R,4R,5R)-4-[[(2R,3S,4R,5R)-5-(6-amino-8-methylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methyl [(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate1309499: Induction of recombinant human RNase L activity expressed in Escherichia coli using F-5’-r(C11U2C7)-3’ as substrate by polyacrylamide gel electrophoresisec500.1340uM
[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxymethyl-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]phosphinic acid671695: Activation of human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-rC11-UU-C7-BHQ2 as substrate by FRET assayec500.2000uM
[4-(6-aminopurin-9-yl)-3-[[4-(6-aminopurin-9-yl)-2,3-dihydroxycyclopentyl]methoxy-hydroxyphosphoryl]oxy-2-hydroxycyclopentyl]methyl [5-(6-aminopurin-9-yl)-2-hydroxy-3-(phosphonooxymethyl)cyclopentyl] hydrogen phosphate166870: Inhibitory activity to prevent binding of added ppp5’A2’p5’A2’pA2’p5’A3’[32P]p5’ (c3 label) to RNase L in human Daudi lymphoblastoid cellsic500.2100uM
[(2R,3S,4R,5R)-5-(6-aminopurin-7-yl)-2-[[[(2R,3R,4R,5R)-2-(6-aminopurin-7-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-7-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-7-yl)-4-(2,2-dimethylpropanoyloxymethoxy)-5-[[hydroxy-[hydroxy(phosphonooxy)phosphoryl]oxyphosphoryl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-(2,2-dimethylpropanoyloxymethoxy)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-(2,2-dimethylpropanoyloxymethoxy)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxymethyl 2,2-dimethylpropanoate763856: Activation of human recombinant RNase L endonuclease activity using 6-FAM-UUA UCA AAU UCU UAU UUG CCC CAU UUU UUU GGU UUA-BHQ-1 as substrate assessed as substrate cleavage measured for 50 mins by FRET assayec500.2410uM
[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-[[(2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl]oxymethyl]phosphinic acid671695: Activation of human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-rC11-UU-C7-BHQ2 as substrate by FRET assayec500.3000uM
[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxymethyl-[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxyphosphinic acid671695: Activation of human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-rC11-UU-C7-BHQ2 as substrate by FRET assayec500.3000uM
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxymethylphosphonic acid671695: Activation of human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-rC11-UU-C7-BHQ2 as substrate by FRET assayec500.3000uM
[(2R,3S,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxymethyl-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]phosphinic acid671695: Activation of human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-rC11-UU-C7-BHQ2 as substrate by FRET assayec501.0000uM
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxymethyl-[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl]oxyphosphinic acid671695: Activation of human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-rC11-UU-C7-BHQ2 as substrate by FRET assayec501.0000uM
[(2R,3R,4S,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methoxymethylphosphonic acid671695: Activation of human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-rC11-UU-C7-BHQ2 as substrate by FRET assayec501.0000uM
2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one1820774: Inhibition of full length H-RNAase L expressed in Escherichia coli BL21 (DE3) assessed as inhibition rate incubated for 15 min in presence of 5 nM 2-5A for 15 mins by Coomassie staining based SDS-PAGE analysisic501.3200uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
2’,5’-oligoadenylateincreases uptake, affects binding, increases activity, increases expression2
Silicon Dioxidedecreases expression, increases expression2
alpha-pineneaffects cotreatment, increases oxidation, increases abundance1
pirinixic aciddecreases expression, increases activity, affects binding1
bisphenol Aincreases expression1
trichostatin Aincreases expression1
sodium arseniteincreases expression1
hydroquinonedecreases expression1
methacrylaldehydeincreases abundance, affects cotreatment, increases oxidation1
CGP 52608affects binding, increases reaction1
erastinincreases expression, increases reaction1
abrinedecreases expression1
jinfukangaffects cotreatment, increases expression1
Acroleinincreases oxidation, increases abundance, affects cotreatment1
Air Pollutantsaffects cotreatment, increases abundance, increases oxidation1
Air Pollutants, Occupationaldecreases expression1
Arsenicaffects methylation1
Benzo(a)pyreneincreases methylation1
Calcitriolincreases expression, affects cotreatment1
Camptothecinincreases expression1
Cisplatinaffects cotreatment, increases expression1
Doxycyclineincreases expression, increases reaction1
Glucoseaffects binding, increases activity, increases uptake1
Nickeldecreases expression1
Ozoneaffects cotreatment, increases oxidation, increases abundance1
Testosteroneincreases expression, affects cotreatment1
Tobacco Smoke Pollutionincreases expression1
Tretinoinincreases expression1
Valproic Acidincreases expression1
Cyclosporinedecreases expression1

ChEMBL screening assays

43 unique, capped per target: 42 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1065130BindingInhibition of human RNaseL ANK domain expressed in Escherichia coli assessed as 5’ flurescein-r(C11U2C7)-3’ RNA cleavage5’-O-dephosphorylated 2’,5’-oligoadenylate (2-5A) with 8-methyladenosine at the 2’-terminus activates human RNase L. — Bioorg Med Chem Lett
CHEMBL2060469FunctionalAntagonist activity at human RNase L expressed in Escherichia coli BL21 (DE3) cells assessed as RNA cleavage using Cy5-C11-rUU-C7-BHQ2 as substrate by FRET assay in presence of natural activator pAAAAActivation of human RNase L by 2’- and 5’-O-methylphosphonate-modified oligoadenylates. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_D7HCUbigene HEK293T RNASEL KOTransformed cell lineFemale
CVCL_F1MEHyCyte A-549 KO-hRNASELCancer cell lineMale
CVCL_TJ21HAP1 RNASEL (-) 1Cancer cell lineMale
CVCL_TJ22HAP1 RNASEL (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT00029224PHASE4COMPLETEDTreatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997PHASE4COMPLETEDOpen-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609PHASE4COMPLETEDThe Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623PHASE4SUSPENDEDThe Plenaxis® Experience Study
NCT00106392PHASE4COMPLETEDA Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029PHASE4UNKNOWNMR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485PHASE4COMPLETEDAngelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219PHASE4COMPLETEDZoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271PHASE4COMPLETEDEffect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146PHASE4COMPLETEDStudy to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554PHASE4COMPLETEDOpen-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098PHASE4COMPLETEDDocetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696PHASE4COMPLETEDCasodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139PHASE4COMPLETEDEffect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765PHASE4COMPLETEDEffects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690PHASE4COMPLETEDEvaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708PHASE4COMPLETEDLocal Anesthesia for Prostate Biopsy
NCT00526331PHASE4COMPLETEDEvaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213PHASE4COMPLETEDCompare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330PHASE4TERMINATEDDissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966PHASE4COMPLETEDRadical Prostatectomy and Perioperative Fluid Therapy
NCT00805701PHASE4COMPLETEDStudy Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027PHASE4COMPLETEDEffect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269PHASE4UNKNOWNCan Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277PHASE4COMPLETEDStudy of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800PHASE4COMPLETEDDoes Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199PHASE4COMPLETEDGlobal Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226PHASE4COMPLETEDEvaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563PHASE4COMPLETEDRandomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905PHASE4COMPLETEDStudy to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672PHASE4COMPLETED3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143PHASE4TERMINATEDProspective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742PHASE4UNKNOWNComparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563PHASE4COMPLETEDHydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874PHASE4COMPLETEDEfficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472PHASE4TERMINATEDFirmagon (Degarelix) Intermittent Therapy
NCT01547416PHASE4COMPLETEDThe Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544PHASE4COMPLETEDThe Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749PHASE4UNKNOWNEvaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635PHASE4COMPLETEDStudy of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer