Protein / target

Guanylate cyclase soluble subunit beta-1

GUCY1B1Q02153Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
10
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Protein-containing complex binding

Primary system

Nervous system

Strongest disease association

hypertensive disorder

Genetic evidence · score 0.56

Therapeutic maturity

Clinically validated target

10 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

10 approved · 5 in clinical development

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

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

Subcellular location

Cytoplasm
Domains and Gene Ontology detail (22)

Domains & features

H-NOXGuanylate cyclase

Gene Ontology

  • Ccytosol
  • Cglutamatergic synapse
  • Cguanylate cyclase complex, soluble
  • Cpresynaptic active zone cytoplasmic component
  • Fadenylate cyclase activity
  • Fcytidylate cyclase activity
  • FGTP binding
  • Fguanylate cyclase activity
  • Fheme binding
  • FHsp90 protein binding
  • Fmetal ion binding
  • Fnitric oxide binding

619 aa · 71 kDa · 3 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingGOExcitatory neurotransmissionGOMuscle contractionReactome
View supporting evidence

Synaptic signalling

  • ·glutamatergic synapse
  • ·presynaptic active zone cytoplasmic component

Excitatory neurotransmission

  • ·glutamatergic synapse

Muscle contraction

  • ·Smooth Muscle Contraction
View underlying pathways (2)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

GUCY1A1GUCY1A2PRKG1PRKG2NOS1ITPAPKLRENPP3ENPP1PKMGUCY1B1

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

2

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Nitric Oxide
ApprovedActivator

Soluble guanylate cyclase activator

Appears in clinical studies involving pulmonary arterial hypertension, respiratory failure, pulmonary hypertension, Hypertension

Acts on a complex — shared with GUCY1B2, GUCY1A2, GUCY1A1 · 1 of 4 recorded protein targets

riociguat
ApprovedPositive allosteric modulator

Soluble guanylate cyclase positive allosteric modulator

Appears in clinical studies involving chronic thromboembolic pulmonary hypertension, pulmonary arterial hypertension, hypertensive disorder, pulmonary hypertension

Acts on a complex — shared with GUCY1B2, GUCY1A2, GUCY1A1 · 1 of 4 recorded protein targets

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

hypertensive disorder0.56

Genetic · overall 0.65

angina pectoris0.50

Genetic · overall 0.68

myocardial infarction0.23

Genetic · overall 0.59

coronary artery disorder0.21

Genetic · overall 0.64

heart failure0.17

Genetic · overall 0.61

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

pulmonary arterial hypertension0.95

Clinical · overall 0.58

cardiovascular disorder0.93

Clinical · overall 0.59

pulmonary hypertension0.92

Clinical · overall 0.56

chronic thromboembolic pulmonary hypertension0.87

Clinical · overall 0.53

respiratory failure0.86

Clinical · overall 0.52

Show all associations
angina pectoris0.68
hypertensive disorder0.65
coronary artery disorder0.64
heart failure0.61
cardiovascular disorder0.59
myocardial infarction0.59
pulmonary arterial hypertension0.58
pulmonary hypertension0.56
chronic thromboembolic pulmonary hypertension0.53
respiratory failure0.52

Open Targets ranks 302 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 15 total

ISOSORBIDE MONONITRATEApproval

coronary artery disorder · cardiovascular disorder · Hydrocephalus

OLINCIGUATPhase 2

Achalasia · sickle cell disease

RUNCACIGUATPhase 2

chronic kidney disease · non-proliferative diabetic retinopathy · diabetes mellitus

RIOCIGUATApproval

chronic thromboembolic pulmonary hypertension · pulmonary arterial hypertension · hypertensive disorder

NITROPRUSSIDEApproval

hypertensive disorder · Hypertension · myocardial infarction

SODIUM NITROPRUSSIDEApproval

hemorrhage · congestive heart failure · Hypertension

ISOSORBIDE DINITRATEApproval

angina pectoris · coronary artery disorder · cardiovascular disorder

PENTAERYTHRITOL TETRANITRATEApproval

cardiovascular disorder · angina pectoris · type 2 diabetes mellitus

CINACIGUATPhase 2

heart failure

NITRIC OXIDEApproval

pulmonary arterial hypertension · respiratory failure · pulmonary hypertension

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · Database UbiquitinationPR · Small Molecule Binder

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Show remaining trials (24)

COMPLETED · via Nitric Oxide · NCT00987207

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

angina pectorisWell supported
0.87
agreement 0.770.97
Clinical60%Genetic40%

Open Targets aggregate 0.68 · 2 independent evidence families

hypertensive disorderWell supported
0.87
agreement 0.760.97
Clinical55%Genetic45%Literature1%

Open Targets aggregate 0.65 · 3 independent evidence families

coronary artery disorderWell supported
0.80
agreement 0.690.91
Clinical78%Genetic22%Literature1%

Open Targets aggregate 0.64 · 3 independent evidence families

heart failureWell supported
0.77
agreement 0.660.87
Clinical81%Genetic19%

Open Targets aggregate 0.61 · 2 independent evidence families

myocardial infarctionWell supported
0.75
agreement 0.650.86
Clinical74%Genetic25%Literature1%

Open Targets aggregate 0.59 · 3 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

33

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. CHMP positive opinion2026-07-20

    CHMP positive opinion: Riociguat Accord (EMA)

    ema · regulatory · ema · via riociguat

  2. New publication2025-04-08
    Understanding chronic inflammation: couplings between cytokines, ROS, NO, Ca<sub>i</sub> <sup>2+</sup>, HIF-1α, Nrf2 and autophagy.

    Frontiers in immunology · 2025 · 37 citations · Europe PMC · via Nitric Oxide

  3. New publication2025-01-01
    Neurological Manifestations Following Traumatic Brain Injury: Role of Behavioral, Neuroinflammation, Excitotoxicity, Nrf-2 and Nitric Oxide.

    CNS & neurological disorders drug targets · 2025 · 5 citations · Europe PMC · via Nitric Oxide

  4. New publication2024-12-11
    Systemic and Cardiac Microvascular Dysfunction in Hypertension.

    International journal of molecular sciences · 2024 · 34 citations · Europe PMC · via Nitric Oxide

  5. New publication2024-08-21
    The Unexpected Role of the Endothelial Nitric Oxide Synthase at the Neurovascular Unit: Beyond the Regulation of Cerebral Blood Flow.

    International journal of molecular sciences · 2024 · 12 citations · Europe PMC · via Nitric Oxide

  6. New publication2024-07-25
    Ca<sup>2+</sup>-dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses.

    Cell reports · 2024 · 6 citations · Europe PMC · via Nitric Oxide

  7. New publication2024-03-14
    Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants.

    Archives of toxicology · 2024 · 563 citations · Europe PMC · via Nitric Oxide

  8. New publication2024-02-20
    A multidisciplinary study on Clinostomum infections in Nile tilapia: micro-morphology, oxidative stress, immunology, and histopathology.

    BMC veterinary research · 2024 · 12 citations · Europe PMC · via Nitric Oxide

  9. New publication2023-09-19
    Neuronal Nitric Oxide Synthase and Post-Translational Modifications in the Development of Central Nervous System Diseases: Implications and Regulation.

    Molecules (Basel, Switzerland) · 2023 · 12 citations · Europe PMC · via Nitric Oxide

  10. New publication2023-09-16
    Modulation of the nitric oxide/cGMP pathway in cardiac contraction and relaxation: Potential role in heart failure treatment.

    Pharmacological research · 2023 · 24 citations · Europe PMC · via Nitric Oxide

  11. New publication2020-02-22
    Vitamin D and Endothelial Function.

    Nutrients · 2020 · 216 citations · Europe PMC · via Nitric Oxide

  12. New publication2020-02-04
    Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase.

    Nature communications · 2020 · 369 citations · Europe PMC · via Nitric Oxide

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.