GUCY1A1: Guanylate Cyclase 1 Soluble Subunit Alpha 1
Key regulator of the nitric oxide (NO)-cGMP signaling pathway, involved in vascular smooth muscle relaxation and platelet aggregation.
Gene Information Card
| Symbol | GUCY1A1 |
|---|---|
| Full Name | Guanylate Cyclase 1 Soluble Subunit Alpha 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q32.1 |
| NCBI Gene ID | 2982 ncbi.nlm.nih.gov/gene/2982 |
| Ensembl ID | ENSG00000164118 |
| UniProt ID | Q02108 |
| OMIM ID | 139396 |
| HGNC ID | 4683 |
| Aliases | GC-SA3, GUC1A1, GUCSA3, alpha-1 subunit |
Description
The GUCY1A1 gene encodes the alpha-1 subunit of soluble guanylyl cyclase (sGC), a heterodimeric enzyme that catalyzes the conversion of GTP to cyclic GMP (cGMP) in response to nitric oxide (NO). This enzyme is a key mediator of the NO-cGMP signaling pathway, regulating vascular smooth muscle relaxation, platelet aggregation, and neurotransmission. Mutations and variants in GUCY1A1 are associated with essential hypertension, moyamoya disease, and other vascular disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Essential Hypertension | Impaired NO-sGC-cGMP signaling due to reduced sGC activity or expression | ClinVar, OMIM #139396 |
| Moyamoya Disease 5 (MYMY5) | Loss-of-function variants in GUCY1A1 disrupt vascular smooth muscle relaxation, leading to cerebrovascular occlusion | OMIM #614042, ClinVar |
| Pulmonary Hypertension | Dysregulation of sGC activity contributes to pulmonary vascular remodeling | NCBI Gene, literature |
| Coronary Artery Disease | Reduced cGMP production linked to endothelial dysfunction and atherosclerosis | ClinVar, GWAS studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Heart | 8.3 | Medium |
| Brain | 6.1 | Low |
| Liver | 4.7 | Low |
| Kidney | 9.2 | Medium |
| Skeletal Muscle | 3.8 | Low |
| Blood | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 15.0 | High expression |
| A549 (lung carcinoma) | 8.5 | Moderate expression |
| HEK293 (embryonic kidney) | 6.2 | Low expression |
| K562 (leukemia) | 2.3 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1471C>T (p.Arg491*) | Nonsense | <0.01% | Loss of function; associated with moyamoya disease |
| c.1123G>A (p.Gly375Arg) | Missense | <0.01% | Impaired heterodimerization with beta subunit |
| c.1790A>G (p.Tyr597Cys) | Missense | 0.02% | Reduced catalytic activity; linked to hypertension |
| c.204+1G>A | Splice donor | <0.01% | Splicing defect; loss of protein function |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site mutations that reduce or abolish sGC activity, leading to impaired NO-cGMP signaling and vascular dysfunction.
Gain of Function (GOF)
Not reported in GUCY1A1; gain-of-function mutations are rare and not documented in major databases.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly375Arg) that disrupt heterodimer formation with the beta subunit, acting in a dominant-negative manner to reduce overall sGC activity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Nitric oxide stimulates guanylate cyclase (Reactome: R-HSA-392154)
• cGMP signaling pathway (KEGG: hsa04722)
• Vascular smooth muscle contraction (KEGG: hsa04270)
• Platelet activation (KEGG: hsa04611)
Protein Summary
The GUCY1A1 protein (alpha-1 subunit) forms a heterodimer with the beta-1 subunit (GUCY1B1) to constitute the soluble guanylyl cyclase enzyme. It contains a heme-binding domain that senses nitric oxide (NO), leading to a conformational change that activates cGMP synthesis. The alpha-1 subunit is essential for catalytic activity and regulation of the NO-sGC-cGMP pathway. Post-translational modifications include phosphorylation and S-nitrosylation, which modulate enzyme activity. The protein is predominantly expressed in vascular smooth muscle, platelets, and brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GUCY1A1 Knockout HEK293 Cell Line | EDJ-KQ1854 | Human | 2982 | Details Get a Quote |
| GUCY1A1 Knockout HeLa Cell Line | EDJ-KQ53460 | Human | 2982 | Details Get a Quote |
| GUCY1A1 Knockout A-549 Cell Line | EDJ-KQ61932 | Human | 2982 | Details Get a Quote |
| GUCY1A1 Knockout HCT 116 Cell Line | EDJ-KQ70413 | Human | 2982 | Details Get a Quote |
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