Protein / target
Guanylate cyclase soluble subunit alpha-2
Protein at a glance
Biological role
Guanylate cyclase
Strongest disease association
Hypertension
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Alpha subunit of soluble guanylate cyclase (sGC), a central enzyme in nitric oxide (NO) signaling.
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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.
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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.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
Broader indication categories (1)Hide
Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.
10 medicines meet Open Targets' target-level approved-medicine definition; the 3 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
Soluble guanylate cyclase activator
Indicated for Hypertension, Pulmonary, Respiratory Insufficiency, Respiratory Tract Diseases
Soluble guanylate cyclase positive allosteric modulator
Indicated for Familial Primary Pulmonary Hypertension, Hypertension, Hypertension, Pulmonary
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene GUCY1A2
Gene-level evidence surfaced through the gene GUCY1A2that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
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 per-type scores above show the calculation.
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Drug development
15 compounds recorded · 10 approved · 5 in clinical development
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Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Protein degraders — Emerging
View underlying tractability evidence (5)Hide
Raw Open Targets tractability assessment buckets, by modality.
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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- Supplemental approval
Supplemental approval: RIOCIGUAT (ANDA211135)
- Supplemental approval
Supplemental approval: RIOCIGUAT (NDA204819)
- CHMP positive opinion
CHMP positive opinion: Riociguat Accord (EMA)
- Supplemental approval
Supplemental approval: RIOCIGUAT (ANDA211135)
- Supplemental approval
Supplemental approval: RIOCIGUAT (NDA204819)
- 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.
- Safety communication
Drug Safety Update: Riociguat (Adempas): not for use in patients with pulmonary hypertension associated with idiopathic interstitial pneumonias
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.