GUCY1B1

gene
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Also known as GC-SB3GC-S-beta-1

Summary

GUCY1B1 (guanylate cyclase 1 soluble subunit beta 1, HGNC:4687) is a protein-coding gene on chromosome 4q32.1, encoding Guanylate cyclase soluble subunit beta-1 (Q02153). Mediates responses to nitric oxide (NO) by catalyzing the biosynthesis of the signaling molecule cGMP.

This gene encodes the beta subunit of the soluble guanylate cyclase (sGC), which catalyzes the conversion of GTP (guanosine triphosphate) to cGMP (cyclic guanosine monophosphate). The encoded protein contains an HNOX domain, which serves as a receptor for ligands such as nitric oxide, oxygen and nitrovasodilator drugs. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2983 — RefSeq curated summary.

At a glance

  • GWAS associations: 10
  • Clinical variants (ClinVar): 55 total
  • Druggable target: yes — 2 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_000857

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:4687
Approved symbolGUCY1B1
Nameguanylate cyclase 1 soluble subunit beta 1
Location4q32.1
Locus typegene with protein product
StatusApproved
AliasesGC-SB3, GC-S-beta-1
Ensembl geneENSG00000061918
Ensembl biotypeprotein_coding
OMIM139397
Entrez2983

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 18 protein_coding

ENST00000264424, ENST00000502959, ENST00000503520, ENST00000505154, ENST00000505764, ENST00000507146, ENST00000513437, ENST00000652626, ENST00000879916, ENST00000879917, ENST00000879918, ENST00000879919, ENST00000879920, ENST00000936140, ENST00000971852, ENST00000971853, ENST00000971854, ENST00000971855

RefSeq mRNA: 6 — MANE Select: NM_000857 NM_000857, NM_001291951, NM_001291952, NM_001291953, NM_001291954, NM_001291955

CCDS: CCDS47154, CCDS75203, CCDS77975, CCDS77976, CCDS77977, CCDS77978

Canonical transcript exons

ENST00000264424 — 14 exons

ExonStartEnd
ENSE00000385694155789714155789911
ENSE00000740142155805103155805229
ENSE00000740145155804593155804747
ENSE00000740150155802342155802579
ENSE00000740152155799877155800074
ENSE00000740154155796377155796510
ENSE00000740156155795341155795457
ENSE00000740158155793856155794086
ENSE00000856058155803624155803764
ENSE00001716583155806386155807811
ENSE00002034801155759021155759143
ENSE00003534048155759787155759860
ENSE00003624850155777524155777642
ENSE00003662474155774968155775068

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.4432 / max 574.1446, expressed in 1185 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
5021514.04391175
502140.3300125
502160.069441

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
middle temporal gyrusUBERON:000277198.32gold quality
orbitofrontal cortexUBERON:000416797.84gold quality
lateral nuclear group of thalamusUBERON:000273697.44gold quality
superior frontal gyrusUBERON:000266197.43gold quality
Brodmann (1909) area 46UBERON:000648397.33gold quality
postcentral gyrusUBERON:000258196.97gold quality
Brodmann (1909) area 23UBERON:001355496.90gold quality
parietal lobeUBERON:000187296.85gold quality
substantia nigra pars compactaUBERON:000196596.82gold quality
ponsUBERON:000098896.75gold quality
entorhinal cortexUBERON:000272896.64gold quality
superior vestibular nucleusUBERON:000722796.36gold quality
lateral globus pallidusUBERON:000247696.10gold quality
substantia nigra pars reticulataUBERON:000196695.67gold quality
CA1 field of hippocampusUBERON:000388195.52gold quality
blood vessel layerUBERON:000479795.51gold quality
prefrontal cortexUBERON:000045195.33gold quality
heart right ventricleUBERON:000208095.05gold quality
ventral tegmental areaUBERON:000269194.87gold quality
dorsolateral prefrontal cortexUBERON:000983494.86gold quality
type B pancreatic cellCL:000016994.85gold quality
Brodmann (1909) area 10UBERON:001354194.59gold quality
urethraUBERON:000005794.48gold quality
frontal cortexUBERON:000187094.36gold quality
endothelial cellCL:000011594.32gold quality
Brodmann (1909) area 9UBERON:001354094.31gold quality
nucleus accumbensUBERON:000188294.17gold quality
cerebral cortexUBERON:000095693.77gold quality
neocortexUBERON:000195093.71gold quality
visceral pleuraUBERON:000240193.65gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

ExperimentMarker?Max mean expression
E-CURD-112yes38.11
E-HCAD-11yes21.51
E-MTAB-8410yes16.06
E-ANND-3yes13.12
E-MTAB-9067yes12.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GFI1, NFIC

miRNA regulators (miRDB)

113 targeting GUCY1B1, 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-5692A100.0074.406850
HSA-MIR-340-5P100.0072.504437
HSA-LET-7A-3P100.0074.033932
HSA-LET-7B-3P100.0074.083913
HSA-LET-7F-1-3P100.0074.023928
HSA-MIR-98-3P100.0074.083907
HSA-MIR-4776-3P100.0068.731340
HSA-MIR-4789-5P99.9870.762721
HSA-MIR-548N99.9871.944170
HSA-MIR-1213699.9872.815713
HSA-LET-7F-2-3P99.9870.982588
HSA-MIR-1185-1-3P99.9871.042593
HSA-MIR-1185-2-3P99.9871.042593
HSA-MIR-569699.9872.364487
HSA-MIR-3065-5P99.9771.563281
HSA-MIR-548AN99.9770.912817
HSA-MIR-365899.9673.874379
HSA-MIR-548AJ-3P99.9673.385345
HSA-MIR-548X-3P99.9673.385345
HSA-MIR-548AB99.9571.313488
HSA-MIR-55999.9572.283609
HSA-MIR-548A-5P99.9471.273482
HSA-MIR-548AD-5P99.9471.233502
HSA-MIR-548AE-5P99.9471.233502
HSA-MIR-548AK99.9471.243488
HSA-MIR-548AM-5P99.9471.243488
HSA-MIR-548AR-5P99.9471.283515
HSA-MIR-548AU-5P99.9471.243488
HSA-MIR-548AY-5P99.9471.233502
HSA-MIR-548B-5P99.9471.233502

Literature-anchored findings (GeneRIF, showing 16)

  • Although soluble guanylate cyclase(sGC) beta1-subunit expression was increased in mononuclear cells from patients with erectile dysfunction, the sGC activity was reduced (PMID:16528291)
  • Results show that NOGCbeta1 and GC-A interact and that NOGCbeta1 regulates atrial natriuretic peptide signaling in HK-2 cells. (PMID:20024606)
  • recombinant soluble guanylate cyclase (sGC) beta1 subunit and truncated N-terminal fragments expressed in E. coli; studied interaction between NO and sGC and schematic mechanism was proposed; study provides insights into structure and NO-binding of sGC (PMID:20063108)
  • The mutant analysis indicated an importance for not only certain dimerization residue positions, but also an important role for other faces of the coiled coil dimer which might perhaps interact with adjacent domains (PMID:20105301)
  • Data show that show that it is possible to directly monitor the sGC haem oxidation state in intact cells. By inserting the TC motif into the coding sequence of the beta1 subunit of sGC in transiently transfected Chinese hamster ovary cells. (PMID:21858179)
  • We concluded that the alpha-subunit and the beta(1)(191-619) domain exert structural strains on the heme domain. (PMID:22223482)
  • The results indicate that in comparison with the alpha-1 beta-1 isoform, the brain alpha-2 beta-1 isoform exhibits a distinctly different CO/NO affinity and binding rate in favor of NO signaling. (PMID:22426988)
  • The G-protein regulator LGN modulates the activity of the NO receptor soluble guanylate cyclase (PMID:22690686)
  • Gene expression in dendritic cells of CCL5 and CXCL5 as well as TIMP1 and GUCY1B3 showed a significant increase within the first 4 days after trauma. (PMID:23179318)
  • Dynamic interplay between hsp90, apo-sGC-beta1, and sGC-alpha1 in response to NO is unprecedented and represent new steps by which cells can modulate the heme content and activity of sGC for signaling cascades. (PMID:24733395)
  • The kinetics of heme loss from oxidized sGC was monitored by a new method based on the heme group de-quenching the fluorescence of FlAsH-EDT2. (PMID:26876536)
  • Inhibition of HDAC3 with targeted therapy could benefit treatment of the diseases associated with sGCbeta1 down-regulation and/or deficiency such as cancer and several vascular-related diseases. (PMID:27279362)
  • Human Red Blood Cells carry catalytically active alpha1beta1-soluble guanylate cyclase (isoform 1). Red cell soluble guanylate cyclase activity is fully preserved in patients with stable coronary artery disease. (PMID:29024896)
  • Our observations revealed that rs7638A/C polymorphism of GUCY1B3 and the longer telomere length inclined toward adaptation to high altitude. (PMID:29443612)
  • Results suggest mechanistic insights into the molecular pathway for soluble guanylyl cyclase (sGC) activation. (PMID:31645439)
  • Inflammation in the Human Periodontium Induces Downregulation of the alpha1- and beta1-Subunits of the sGC in Cementoclasts. (PMID:33430449)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriogucy1b1ENSDARG00000086790
mus_musculusGucy1b1ENSMUSG00000028005
rattus_norvegicusGucy1b1ENSRNOG00000012060
drosophila_melanogasterGycbeta100BFBGN0013973

Paralogs (17): GUCY2C (ENSG00000070019), ADCY2 (ENSG00000078295), GUCY2F (ENSG00000101890), NPR3 (ENSG00000113389), ADCY7 (ENSG00000121281), ADCY4 (ENSG00000129467), GUCY2D (ENSG00000132518), ADCY3 (ENSG00000138031), GUCY1A2 (ENSG00000152402), ADCY8 (ENSG00000155897), NPR2 (ENSG00000159899), ADCY9 (ENSG00000162104), GUCY1A1 (ENSG00000164116), ADCY1 (ENSG00000164742), NPR1 (ENSG00000169418), ADCY5 (ENSG00000173175), ADCY6 (ENSG00000174233)

Protein

Protein identifiers

Guanylate cyclase soluble subunit beta-1Q02153 (reviewed: Q02153)

Alternative names: Guanylate cyclase soluble subunit beta-3, Soluble guanylate cyclase small subunit

All UniProt accessions (5): Q02153, A0A494C1B9, B7Z685, D6RC99, E9PCN2

UniProt curated annotations — full annotation on UniProt →

Function. Mediates responses to nitric oxide (NO) by catalyzing the biosynthesis of the signaling molecule cGMP.

Subunit / interactions. The active enzyme is formed by a heterodimer of an alpha and a beta subunit. Heterodimer with GUCY1A1. Can also form inactive homodimers in vitro.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in brain cortex and cerebellum (at protein level).

Activity regulation. Activated by nitric oxide in the presence of magnesium or manganese ions.

Cofactor. Binds 1 or 2 heme groups per heterodimer. Heme is required for responding to nitric oxide, but not for catalytic activity.

Miscellaneous. There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms.

Similarity. Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.

Isoforms (3)

UniProt IDNamesCanonical?
Q02153-1HSGC-1yes
Q02153-2HSGC-2
Q02153-33

RefSeq proteins (6): NP_000848, NP_001278880, NP_001278881, NP_001278882, NP_001278883, NP_001278884 (=MANE)

Domains & families (InterPro)

IDNameType
IPR001054A/G_cyclaseDomain
IPR011644Heme_NO-bdDomain
IPR011645HNOB_dom_associatedDomain
IPR018297A/G_cyclase_CSConserved_site
IPR024096NO_sig/Golgi_transp_ligand-bdHomologous_superfamily
IPR029787Nucleotide_cyclaseHomologous_superfamily
IPR038158H-NOX_domain_sfHomologous_superfamily
IPR042463HNOB_dom_associated_sfHomologous_superfamily

Pfam: PF00211, PF07700, PF07701

Enzyme classification (BRENDA):

  • EC 4.6.1.2 — guanylate cyclase (BRENDA: 58 organisms, 213 substrates, 212 inhibitors, 100 Km, 16 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
GTP0.01–6.0990
2’-O-(N-METHYLANTHRANILOYL) GUANOSINE 5’-TRIPHOS0.03571
GUANYL-(BETA,GAMMA-METHYLENE)-DIPHOSPHONATE0.371
GUANYL-IMIDODIPHOSPHATE0.071
MN2+2.71

Catalyzed reactions (Rhea), 1 shown:

  • GTP = 3’,5’-cyclic GMP + diphosphate (RHEA:13665)

UniProt features (60 total): strand 25, helix 22, turn 8, splice variant 2, chain 1, domain 1, binding site 1

Structure

Experimental structures (PDB)

14 structures.

PDBMethodResolution (Å)
2WZ1X-RAY DIFFRACTION1.63
4NI2X-RAY DIFFRACTION1.9
3UVJX-RAY DIFFRACTION2.08
8HBFELECTRON MICROSCOPY3.1
8HBHELECTRON MICROSCOPY3.1
8HBEELECTRON MICROSCOPY3.2
7D9RELECTRON MICROSCOPY3.7
6JT2ELECTRON MICROSCOPY3.8
7D9UELECTRON MICROSCOPY3.8
6JT1ELECTRON MICROSCOPY3.9
7D9SELECTRON MICROSCOPY3.9
6JT0ELECTRON MICROSCOPY4
7D9TELECTRON MICROSCOPY4.1
5MNWSOLUTION NMR

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q02153-F185.390.42

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 (1): 105 (proximal binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-392154Nitric oxide stimulates guanylate cyclase
R-HSA-445355Smooth Muscle Contraction

MSigDB gene sets: 251 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, chr4q32, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CGMP_BIOSYNTHETIC_PROCESS, GOZGIT_ESR1_TARGETS_DN, MODULE_445, MODULE_65, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CYCLIC_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS

GO Biological Process (9): cGMP biosynthetic process (GO:0006182), obsolete nitric oxide mediated signal transduction (GO:0007263), blood circulation (GO:0008015), obsolete cGMP-mediated signaling (GO:0019934), nitric oxide-cGMP-mediated signaling (GO:0038060), response to oxygen levels (GO:0070482), cellular response to nitric oxide (GO:0071732), cyclic nucleotide biosynthetic process (GO:0009190), intracellular signal transduction (GO:0035556)

GO Molecular Function (14): adenylate cyclase activity (GO:0004016), guanylate cyclase activity (GO:0004383), GTP binding (GO:0005525), heme binding (GO:0020037), signaling receptor activity (GO:0038023), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), cytidylate cyclase activity (GO:0047805), Hsp90 protein binding (GO:0051879), nitric oxide binding (GO:0070026), nucleotide binding (GO:0000166), protein binding (GO:0005515), lyase activity (GO:0016829), phosphorus-oxygen lyase activity (GO:0016849)

GO Cellular Component (6): cytosol (GO:0005829), guanylate cyclase complex, soluble (GO:0008074), presynaptic active zone cytoplasmic component (GO:0098831), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
Platelet homeostasis1
Muscle contraction1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cyclase activity3
phosphorus-oxygen lyase activity3
cyclic nucleotide biosynthetic process2
intracellular anatomical structure2
binding2
cellular anatomical structure2
purine ribonucleotide biosynthetic process1
cGMP metabolic process1
circulatory system process1
intracellular signaling cassette1
response to abiotic stimulus1
response to nitric oxide1
cellular response to oxygen-containing compound1
cellular response to reactive nitrogen species1
nucleotide biosynthetic process1
cyclic nucleotide metabolic process1
signal transduction1
cGMP biosynthetic process1
guanyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
tetrapyrrole binding1
molecular transducer activity1
cation binding1
heat shock protein binding1
small molecule binding1
nucleoside phosphate binding1
heterocyclic compound binding1
catalytic activity1
lyase activity1
cytoplasm1
cytosol1
catalytic complex1
presynaptic active zone1
cell cortex region1
synapse1
cellular_component1

Protein interactions and networks

STRING

1138 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
GUCY1B1GUCY1A1Q02108950
GUCY1B1GUCY1A2P33402834
GUCY1B1PDE5AO76074561
GUCY1B1AK8Q96MA6488
GUCY1B1PDE7BQ9NP56486
GUCY1B1PRKG2Q13237451
GUCY1B1NTPCRQ9BSD7451
GUCY1B1PRKG1P14619444
GUCY1B1LY6G6FQ5SQ64441
GUCY1B1DLG4P78352424
GUCY1B1CTSOP43234407
GUCY1B1ATICP31939403
GUCY1B1CANT1Q8WVQ1395
GUCY1B1IRAG1Q9Y6F6390
GUCY1B1GFI1BQ5VTD9385

IntAct

25 interactions, top by confidence:

ABTypeScore
LIN7ACASKpsi-mi:“MI:0914”(association)0.830
GUCY1A1GUCY1B1psi-mi:“MI:0407”(direct interaction)0.670
GUCY1A1GUCY1B1psi-mi:“MI:0883”(gtpase reaction)0.670
GUCY1B1GUCY1B1psi-mi:“MI:0407”(direct interaction)0.440
IMMP2LANKHD1-EIF4EBP3psi-mi:“MI:0914”(association)0.350
ABCD4psi-mi:“MI:0914”(association)0.350
OR1M1NBASpsi-mi:“MI:0914”(association)0.350
ZDHHC12NBASpsi-mi:“MI:0914”(association)0.350
PRKYMETTL15psi-mi:“MI:0914”(association)0.350
OR6T1PSMD11psi-mi:“MI:0914”(association)0.350
HNRNPCL2SMCHD1psi-mi:“MI:0914”(association)0.350
TLR9ABCD4psi-mi:“MI:0914”(association)0.350
ABCA2ABCD4psi-mi:“MI:0914”(association)0.350
GRIN3BDAPK3psi-mi:“MI:0914”(association)0.350
ANKMY2ADCY6psi-mi:“MI:0914”(association)0.350
OR2M7MARCHF6psi-mi:“MI:0914”(association)0.350
SLC12A3SNX2psi-mi:“MI:0914”(association)0.350
GUCY1B1MYCBP2psi-mi:“MI:0914”(association)0.350
USP28OFD1psi-mi:“MI:0914”(association)0.350
NOX5RNASEH2Apsi-mi:“MI:0914”(association)0.350
CHRNA7UFL1psi-mi:“MI:0914”(association)0.350
GUCY1B1MXRA7psi-mi:“MI:0914”(association)0.350
SLC27A6NBASpsi-mi:“MI:0914”(association)0.350
DSCR9GUCY1B1psi-mi:“MI:0915”(physical association)0.000

BioGRID (56): GUCY1B3 (Affinity Capture-MS), GUCY1A2 (Affinity Capture-MS), GUCY1A3 (Affinity Capture-MS), MXRA7 (Affinity Capture-MS), GUCY1B3 (Affinity Capture-MS), UACA (Affinity Capture-MS), GUCY1B3 (Affinity Capture-MS), MTFR2 (Affinity Capture-MS), MYCBP2 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), MUL1 (Affinity Capture-MS), GUCY1B3 (Affinity Capture-RNA), NOS3 (Reconstituted Complex), HSP90AA1 (Reconstituted Complex), NOS3 (Affinity Capture-Western)

ESM2 similar proteins: A0A2R8QFQ6, A0A2R8RWN9, D3Z7P3, E9PV86, G3MWR8, O54865, O60907, O89050, O94925, P13264, P16068, P20595, P58058, Q02153, Q08211, Q12800, Q13042, Q14722, Q28141, Q28D01, Q3MHJ2, Q3ULA2, Q4R8H1, Q4ZHR9, Q5R874, Q5RB35, Q5SP67, Q5SRY7, Q5ZHN3, Q6DN14, Q7RTP6, Q7T2U9, Q7Z6J6, Q8BTG7, Q8C6G8, Q8CJ19, Q8K4Q0, Q8N122, Q8N2K0, Q8R349

Diamond homologs: A0A078BQP2, A0A0U1RPR8, E7EAU8, H2L002, O02298, O02740, O16715, O19179, O54865, O62179, O75343, P0A4Y1, P16065, P16066, P16068, P18293, P18910, P19686, P19687, P20594, P20595, P22717, P23897, P25092, P26770, P33402, P51840, P51841, P51842, P52785, P55202, P55203, P55204, P70106, P90895, P91550, P92006, P9WQ34, P9WQ35, Q02108

SIGNOR signaling

2 interactions.

AEffectBMechanism
GUCY1B1“form complex”GUCY1A2-B3binding
GUCY1B1“form complex”GUCY1A3-B3binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance43
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2338 predictions. Top by Δscore:

VariantEffectΔscore
4:155759782:CGCAG:Cacceptor_loss1.0000
4:155759785:A:AGacceptor_gain1.0000
4:155759785:AGTAC:Aacceptor_gain1.0000
4:155759786:G:GAacceptor_gain1.0000
4:155759786:GT:Gacceptor_gain1.0000
4:155759786:GTAC:Gacceptor_gain1.0000
4:155759786:GTACG:Gacceptor_gain1.0000
4:155759861:G:GGdonor_gain1.0000
4:155774952:T:TAacceptor_gain1.0000
4:155774958:T:TAacceptor_gain1.0000
4:155774964:CCAG:Cacceptor_loss1.0000
4:155774966:A:AGacceptor_gain1.0000
4:155774966:AG:Aacceptor_loss1.0000
4:155774967:G:GAacceptor_gain1.0000
4:155774967:GA:Gacceptor_gain1.0000
4:155774967:GAA:Gacceptor_gain1.0000
4:155774967:GAAA:Gacceptor_gain1.0000
4:155774967:GAAAA:Gacceptor_gain1.0000
4:155775064:CCTCA:Cdonor_gain1.0000
4:155775065:CTCAG:Cdonor_loss1.0000
4:155775066:TCA:Tdonor_gain1.0000
4:155775067:CA:Cdonor_gain1.0000
4:155775067:CAGT:Cdonor_loss1.0000
4:155775068:AGTA:Adonor_loss1.0000
4:155775069:G:GGdonor_gain1.0000
4:155775070:TAAG:Tdonor_loss1.0000
4:155775071:AAGTT:Adonor_loss1.0000
4:155777508:T:Aacceptor_gain1.0000
4:155777511:A:AGacceptor_gain1.0000
4:155777517:A:AGacceptor_gain1.0000

AlphaMissense

4101 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
4:155759790:G:AG3R1.000
4:155759790:G:CG3R1.000
4:155759791:G:AG3E1.000
4:155775053:G:CA55P1.000
4:155777556:G:AG71R1.000
4:155777556:G:CG71R1.000
4:155777556:G:TG71W1.000
4:155777557:G:AG71E1.000
4:155777557:G:TG71V1.000
4:155777578:G:AC78Y1.000
4:155777579:C:GC78W1.000
4:155777605:T:CL87S1.000
4:155777614:T:CL90P1.000
4:155777616:G:CG91R1.000
4:155777616:G:TG91C1.000
4:155777617:G:AG91D1.000
4:155777617:G:TG91V1.000
4:155777634:T:CF97L1.000
4:155777635:T:CF97S1.000
4:155777636:T:AF97L1.000
4:155777636:T:GF97L1.000
4:155777638:T:CL98P1.000
4:155789718:T:AL101H1.000
4:155789718:T:CL101P1.000
4:155789720:G:CD102H1.000
4:155789720:G:TD102Y1.000
4:155789721:A:CD102A1.000
4:155789721:A:TD102V1.000
4:155789727:T:CL104P1.000
4:155789729:C:GH105D1.000

dbSNP variants (sampled 300 via entrez): RS1000028198 (4:155767712 C>T), RS1000181745 (4:155789242 A>C), RS1000214956 (4:155795901 A>G), RS1000241336 (4:155788301 A>G), RS10003470 (4:155788060 A>G), RS1000401243 (4:155780938 A>C,G), RS1000495696 (4:155771386 T>C,G), RS1000728651 (4:155804542 A>G,T), RS1000739942 (4:155804345 C>T), RS1000784620 (4:155778053 A>G), RS1000801418 (4:155786931 A>G), RS1000842573 (4:155788732 G>A), RS1000873490 (4:155760869 C>G), RS1000886782 (4:155757800 T>C), RS1000913272 (4:155807557 T>C)

Disease associations

OMIM: gene MIM:139397 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

StudyTraitp-value
GCST001227_20Systolic blood pressure1.000000e-06
GCST001228_9Diastolic blood pressure2.000000e-10
GCST001236_17Blood pressure3.000000e-07
GCST004278_64Pulse pressure7.000000e-14
GCST004776_19Systolic blood pressure5.000000e-06
GCST004777_5Diastolic blood pressure2.000000e-06
GCST006259_49Systolic blood pressure7.000000e-09
GCST007707_36Hypertension6.000000e-06
GCST009840_2Diabetic retinopathy in type 2 diabetes4.000000e-06
GCST010867_31Coronary artery disease3.000000e-08

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0006335systolic blood pressure
EFO:0006336diastolic blood pressure
EFO:0006340mean arterial pressure
EFO:0005763pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111348 (PROTEIN COMPLEX GROUP), CHEMBL3137281 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,203 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL12610BENZYDAMINE48,193
CHEMBL5944803FRESPACIGUAT210

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Nitric oxide (NO)-sensitive (soluble) guanylyl cyclase

Binding affinities (BindingDB)

465 measured of 465 human assays (465 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-5-[3-(2H-tetrazol-5-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-6-oneKI0.068 nMUS-10428076: Soluble guanylate cyclase stimulators
3-[2-[4-[(5S)-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]ethyl]-1,2,4-oxadiazolidin-5-oneKI0.074 nMUS-10428076: Soluble guanylate cyclase stimulators
(1R,6S)-3-[6-[2-[[2-[[(2S)-1,4-dioxan-2-yl]methyl]-5-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC501 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-5,8-dimethyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC501 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3S,4S)-3-methoxy-1-[6-[3-methyl-2-[[6-methyl-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-8-yl]methoxy]phenyl]-2-pyridinyl]piperidine-4-carboxylic acidEC501 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3S,4S)-3-methoxy-1-[6-[3-methyl-2-[[6-methyl-3-[(3S)-oxolan-3-yl]-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-2-pyridinyl]piperidine-4-carboxylic acidEC501 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3R,4R)-1-[4-[3-chloro-2-[[(5R)-5-methyl-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-methoxypiperidine-4-carboxylic acidEC501 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3S,4S)-1-[6-[2-[[5,5-dimethyl-3-(oxetan-3-yl)-2,4-dihydro-1H-3-benzazepin-7-yl]methoxy]-3-methylphenyl]-2-pyridinyl]-3-methoxypiperidine-4-carboxylic acidEC501 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[6-[3-methyl-2-[[8-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[6-[5-methyl-2-[[5-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,5R)-3-[6-[3-methyl-2-[[6-methyl-3-(oxetan-3-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[3.1.0]hexane-1-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-5-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[3-methyl-2-[[5-methyl-2-(oxan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[3-methyl-2-[[8-methyl-2-(oxolan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[3-methyl-2-[[8-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[3-methyl-2-[[8-methyl-2-(oxetan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[3-methyl-2-[[6-methyl-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-5-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-5-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-5-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3S,4S)-3-ethoxy-1-[4-[2-[[5-fluoro-8-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]piperidine-4-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3R,4R)-1-[4-[2-[[5-fluoro-8-methoxy-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-methoxypiperidine-4-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3S,4S)-3-ethoxy-1-[4-[2-[[5-fluoro-8-methoxy-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]piperidine-4-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3S,4S)-3-ethoxy-1-[4-[2-[[5-fluoro-8-methoxy-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-5-methylphenyl]-1,3-thiazol-2-yl]piperidine-4-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3S,4S)-3-methoxy-1-[6-[3-methyl-2-[[6-methyl-3-(oxetan-3-yl)-1,2,4,5-tetrahydro-3-benzazepin-8-yl]methoxy]phenyl]-2-pyridinyl]piperidine-4-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[2-[[2-(4,4-difluorocyclohexyl)-8-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3R,4R)-1-[4-[2-[[5,5-dimethyl-3-(oxan-4-yl)-2,4-dihydro-1H-3-benzazepin-7-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-methoxypiperidine-4-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3S,4S)-1-[6-[2-[[5,5-dimethyl-3-(oxan-4-yl)-2,4-dihydro-1H-3-benzazepin-7-yl]methoxy]-3-methylphenyl]-2-pyridinyl]-3-methoxypiperidine-4-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3S,4S)-1-[4-[5-fluoro-3-methyl-2-[[(5R)-5-methyl-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-methoxypiperidine-4-carboxylic acidEC502 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[6-[2-[[5-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[6-[2-[[2-(1,4-dioxan-2-ylmethyl)-5-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[6-[3-methyl-2-[[5-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-8-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[3-methyl-2-[[8-methyl-2-(oxan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[2-[[5,8-dimethyl-2-(oxan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[2-[[5,8-dimethyl-2-(oxolan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[2-[[5,8-dimethyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[2-[[5,8-dimethyl-2-(oxetan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[5-methyl-2-[[5-methyl-2-(oxolan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-5,8-dimethyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-5-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3S,4S)-3-methoxy-1-[6-[3-methyl-2-[[6-methyl-3-(oxetan-3-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-2-pyridinyl]piperidine-4-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,2S,5R)-3-[6-[2-[[6-fluoro-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-8-yl]methoxy]-3-methylphenyl]-2-pyridinyl]-2-(methoxymethyl)-3-azabicyclo[3.1.0]hexane-1-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3R,4R)-1-[6-[3-chloro-2-[[8-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-ethoxypiperidine-4-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3R,4R)-1-[6-[3-chloro-2-[[8-methoxy-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-ethoxypiperidine-4-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3R,4R)-1-[4-[3-chloro-2-[[8-methoxy-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-ethoxypiperidine-4-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,2S,5R)-3-[6-[2-[[6-fluoro-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]-3-methylphenyl]-2-pyridinyl]-2-(methoxymethyl)-3-azabicyclo[3.1.0]hexane-1-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[6-[2-[(2-cyclobutyl-5-methyl-3,4-dihydro-1H-isoquinolin-6-yl)methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(3S,4S)-3-methoxy-1-[6-[3-methyl-2-[[6-methyl-3-[(3R)-oxolan-3-yl]-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-2-pyridinyl]piperidine-4-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[6-[2-[[5-methyl-2-(1-pyridin-2-ylethyl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase
(1R,6S)-3-[6-[2-[[5-methyl-2-[(5-methyl-1,2-oxazol-3-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acidEC503 nMUS-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase

ChEMBL bioactivities

909 potent at pChembl≥5 of 962 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.66Ki0.022nMCHEMBL5814188
10.59Ki0.026nMCHEMBL5961042
10.54Ki0.029nMCHEMBL5937094
10.51Ki0.031nMCHEMBL5962881
10.51Ki0.031nMCHEMBL5896066
10.51Ki0.031nMCHEMBL5828124
10.41Ki0.039nMCHEMBL5754765
10.39Ki0.041nMCHEMBL6025572
10.38Ki0.042nMCHEMBL5943807
10.35Ki0.045nMCHEMBL5924970
10.33Ki0.047nMCHEMBL5980517
10.32Ki0.048nMCHEMBL5989618
10.31Ki0.049nMCHEMBL6038148
10.30Ki0.05nMCHEMBL5915567
10.28Ki0.052nMCHEMBL6021981
10.28Ki0.052nMCHEMBL6053909
10.25Ki0.056nMCHEMBL5838947
10.24Ki0.058nMCHEMBL5925728
10.24Ki0.057nMCHEMBL6031103
10.24Ki0.058nMCHEMBL6006393
10.24Ki0.057nMCHEMBL5959396
10.24Ki0.058nMCHEMBL5981554
10.22Ki0.06nMCHEMBL5872155
10.21Ki0.062nMCHEMBL6055856
10.21Ki0.062nMCHEMBL6011397
10.21Ki0.062nMCHEMBL5946879
10.20Ki0.063nMCHEMBL5973404
10.20Ki0.063nMCHEMBL6050464
10.19Ki0.064nMCHEMBL5941930
10.18Ki0.066nMCHEMBL5850021
10.18Ki0.066nMCHEMBL5754222
10.17Ki0.067nMCHEMBL5758630
10.17Ki0.067nMCHEMBL5842014
10.17Ki0.067nMCHEMBL6019970
10.17Ki0.068nMCHEMBL5996734
10.17Ki0.068nMCHEMBL5870392
10.15Ki0.07nMCHEMBL5979143
10.15Ki0.07nMCHEMBL5977775
10.14Ki0.072nMCHEMBL6065117
10.14Ki0.073nMCHEMBL6023523
10.13Ki0.074nMCHEMBL6064339
10.13Ki0.074nMCHEMBL5908747
10.13Ki0.074nMCHEMBL5862357
10.12Ki0.075nMCHEMBL5855606
10.12Ki0.075nMCHEMBL5981113
10.12Ki0.075nMCHEMBL5793164
10.12Ki0.076nMCHEMBL5965599
10.11Ki0.078nMCHEMBL5828379
10.11Ki0.077nMCHEMBL6032838
10.10Ki0.079nMCHEMBL5972747

PubChem BioAssay actives

72 with measured affinity, of 284 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidine-4-carboxylic acid1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0070uM
1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidin-4-ol1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0100uM
5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-N-methylpyrimidin-4-amine1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0200uM
3-[1-[(2-fluorophenyl)methyl]-3-(5-fluoro-4-piperidin-1-ylpyrimidin-2-yl)pyrazol-5-yl]-1,2-oxazole1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0270uM
1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidin-3-ol1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0330uM
(2R,3S)-1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]-3-methylpiperidine-2-carboxylic acid1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0330uM
[1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidin-2-yl]methanol1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0350uM
(2S,3R)-1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]-3-methylpiperidine-2-carboxylic acid1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0400uM
5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-N-(2-morpholin-4-ylethyl)pyrimidin-4-amine1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0410uM
4-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]morpholine1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0500uM
1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidine-3-carboxylic acid1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0550uM
3-[1-[(2-fluorophenyl)methyl]-3-(5-fluoro-4-pyrrolidin-1-ylpyrimidin-2-yl)pyrazol-5-yl]-1,2-oxazole1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0830uM
5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.0970uM
methyl N-[4,6-diamino-2-[3-[(2,3,5-trifluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.1100uM
6-amino-2-[3-[(2-fluorophenyl)methyl]indazol-1-yl]-7-methyl-9H-purin-8-one1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.1200uM
3-[1-[(2-fluorophenyl)methyl]-3-(5-fluoro-4-piperazin-1-ylpyrimidin-2-yl)pyrazol-5-yl]-1,2-oxazole1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.1200uM
(2R)-1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidine-2-carboxylic acid1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.1200uM
5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-amine1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.1300uM
6-amino-2-[5-chloro-3-[(2-fluorophenyl)methyl]indazol-1-yl]-7-methyl-9H-purin-8-one1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.1400uM
3-[3-[4-(3,3-difluoropiperidin-1-yl)-5-fluoropyrimidin-2-yl]-1-[(2-fluorophenyl)methyl]pyrazol-5-yl]-1,2-oxazole1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.1500uM
4-amino-2-[3-[(2-fluorophenyl)methyl]indazol-1-yl]-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.1600uM
5-(4-chlorophenyl)sulfonyl-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.1600uM
5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-thiazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.1800uM
6-amino-7-ethyl-2-[3-[(2-fluorophenyl)methyl]indazol-1-yl]-9H-purin-8-one1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.2000uM
(2S)-1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidine-2-carboxylic acid1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.2000uM
2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-amine1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.2400uM
5-fluoro-2-[1-[(2-fluoro-3-methylphenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.2400uM
4-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]-1,4-thiazinane 1,1-dioxide1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.2400uM
3-[3-[4-(4,4-difluoropiperidin-1-yl)-5-fluoropyrimidin-2-yl]-1-[(2-fluorophenyl)methyl]pyrazol-5-yl]-1,2-oxazole1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.2500uM
methyl N-[4,6-diamino-2-[3-[(2,5-difluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.2700uM
methyl N-[4,6-diamino-2-[3-[(2,3,6-trifluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.2700uM
5-fluoro-2-[1-[(3-fluorothiophen-2-yl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.2800uM
methyl N-[4,6-diamino-2-[3-[(2,3-difluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.3000uM
6-amino-2-[3-[(2-fluorophenyl)methyl]indazol-1-yl]-7,9-dihydropurin-8-one1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.3000uM
methyl N-[4,6-diamino-2-[3-[(2-fluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.3100uM
3-[3-(5-fluoro-4-methoxypyrimidin-2-yl)-1-[(2-fluorophenyl)methyl]pyrazol-5-yl]-1,2-oxazole1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.3200uM
methyl N-[4,6-diamino-2-[5-chloro-3-[(2-fluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.3500uM
5-(benzenesulfonyl)-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.3500uM
2-[1-[(2,3-difluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-fluoro-1H-pyrimidin-6-one1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.3700uM
2-[1-[(3-chloro-2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-fluoro-1H-pyrimidin-6-one1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.3800uM
2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-6-oxo-1H-pyrimidine-5-carbonitrile1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.5000uM
2-[1-[(2,4-difluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-fluoro-1H-pyrimidin-6-one1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.5300uM
5-chloro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.5900uM
methyl N-[4,6-diamino-2-[5-chloro-3-[(2,3,6-trifluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]carbamate1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.6700uM
methyl N-[4,6-diamino-2-[5-chloro-3-[(2,3,6-trifluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.7000uM
2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-N-methyl-6-oxo-N-phenyl-1H-pyrimidine-5-sulfonamide1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.7300uM
2-[1-benzyl-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-fluoro-1H-pyrimidin-6-one1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.8800uM
2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-methylsulfonyl-1H-pyrimidin-6-one1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOateec500.9000uM
methyl N-[4,6-diamino-2-[5-fluoro-3-[(2-fluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assayec500.9600uM
(2S)-1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]pyrrolidine-2-carboxylic acid1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assayec500.9700uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects expression, increases expression, increases methylation7
bisphenol Adecreases expression, increases expression3
1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-oneincreases activity, increases reaction, affects cotreatment, affects binding, affects folding (+1 more)2
entinostataffects cotreatment, decreases expression2
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoateaffects cotreatment, affects expression1
fluorene-9-bisphenolincreases expression1
methylmercuric chloridedecreases expression1
triphenyl phosphateaffects expression1
propionaldehydeincreases expression1
trichostatin Aincreases expression1
sodium arseniteincreases expression1
butyraldehydeincreases expression1
perfluorooctanoic acidaffects expression, affects cotreatment1
protoporphyrin IXincreases activity, increases reaction, affects binding1
potassium ferricyanideaffects binding, decreases reaction, increases activity1
hydroquinoneincreases expression1
S-(1,2-dichlorovinyl)cysteinedecreases reaction, increases expression1
pentanalincreases expression1
perfluorooctane sulfonic acidaffects expression, affects cotreatment1
1,1-diethyl-2-hydroxy-2-nitrosohydrazineaffects binding, increases activity, decreases reaction1
3-(5’-hydroxymethyl-2’-furyl)-1-benzylindazoleaffects binding, affects folding1
CGP 52608affects binding, increases reaction1
3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridineaffects binding, increases activity, increases reaction1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamidedecreases expression, affects cotreatment1
BAY 58-2667affects binding, affects cotreatment, increases activity, increases reaction1
2,2’,4,4’-tetrabromodiphenyl etherdecreases expression1
dicyanocobinamideaffects binding, increases activity, increases reaction, decreases reaction, increases metabolic processing1
5-chloro-2-(5-chlorothiophene-2-sulfonylamino)-N-(4-(morpholine-4-sulfonyl)phenyl)benzamideaffects binding, increases activity, increases reaction1
dorsomorphinaffects cotreatment, decreases expression1
hexabrominated diphenyl ether 153decreases expression1

ChEMBL screening assays

45 unique, capped per target: 40 binding, 5 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1918701BindingActivation of human soluble guanylate cyclase assessed as production of cGMP in presence of nitric oxide donor, SIN-1 by LC-MS enzyme assayAcidic triazoles as soluble guanylate cyclase stimulators. — Bioorg Med Chem Lett
CHEMBL865676FunctionalEffect on cGMP production in porcine iris-ciliary body at 10 uMSynthesis and ocular effects of imidazole nitrolic acid and amidoxime esters. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): diabetic retinopathy