Protein / target
Guanylate cyclase soluble subunit alpha-2
Protein at a glance
Biological role
Guanylate cyclase activity
Strongest disease association
hypertensive disorder
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
10 approved · 5 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Alpha subunit of soluble guanylate cyclase (sGC), a central enzyme in nitric oxide (NO) signaling. Functions as the main intracellular receptor for NO. Upon NO binding, catalyzes the conversion of GTP to cyclic GMP (cGMP) and thereby transducing NO signal into a ubiquitous intracellular second messenger
Subcellular location
Domains and Gene Ontology detail (10)Hide
Domains & features
Gene Ontology
- Ccytosol
- Cguanylate cyclase complex, soluble
- FGTP binding
- Fguanylate cyclase activity
- Fheme binding
- Pintracellular signal transduction
- Presponse to oxygen levels
- Psignal transduction
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Muscle contraction
- ·Smooth Muscle Contraction
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
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.
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
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.
Soluble guanylate cyclase activator
Appears in clinical studies involving pulmonary arterial hypertension, respiratory failure, pulmonary hypertension, Hypertension
Soluble guanylate cyclase positive allosteric modulator
Appears in clinical studies involving chronic thromboembolic pulmonary hypertension, pulmonary arterial hypertension, hypertensive disorder, pulmonary hypertension
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
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.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 207 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
cardiovascular disorder · angina pectoris · type 2 diabetes mellitus
chronic kidney disease · non-proliferative diabetic retinopathy · diabetes mellitus
hemorrhage · congestive heart failure · Hypertension
heart failure
angina pectoris · coronary artery disorder · cardiovascular disorder
neuropathic pain · peripheral arterial disease
hypertensive disorder · Hypertension · myocardial infarction
angina pectoris · coronary artery disorder · heart failure
pulmonary arterial hypertension · respiratory failure · pulmonary hypertension
Achalasia · sickle cell disease
Tractability
Clinical trials
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)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
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.
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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
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.
- CHMP positive opinion
CHMP positive opinion: Riociguat Accord (EMA)
- New publicationUnderstanding chronic inflammation: couplings between cytokines, ROS, NO, Ca<sub>i</sub> <sup>2+</sup>, HIF-1α, Nrf2 and autophagy.
- New publicationNeurological Manifestations Following Traumatic Brain Injury: Role of Behavioral, Neuroinflammation, Excitotoxicity, Nrf-2 and Nitric Oxide.
- New publicationSystemic and Cardiac Microvascular Dysfunction in Hypertension.
- New publicationThe Unexpected Role of the Endothelial Nitric Oxide Synthase at the Neurovascular Unit: Beyond the Regulation of Cerebral Blood Flow.
- New publicationCa<sup>2+</sup>-dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses.
- New publicationSeveral lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants.
- New publicationA multidisciplinary study on Clinostomum infections in Nile tilapia: micro-morphology, oxidative stress, immunology, and histopathology.
- New publicationNeuronal Nitric Oxide Synthase and Post-Translational Modifications in the Development of Central Nervous System Diseases: Implications and Regulation.
- New publicationModulation of the nitric oxide/cGMP pathway in cardiac contraction and relaxation: Potential role in heart failure treatment.
- New publicationVitamin D and Endothelial Function.
- New publicationNitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase.
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.