GUCY1A2: Guanylate Cyclase 1 Soluble Subunit Alpha 2
A key component of the nitric oxide (NO) signaling pathway, encoding the alpha-2 subunit of soluble guanylyl cyclase.
Gene Information Card
| Symbol | GUCY1A2 |
|---|---|
| Full Name | Guanylate Cyclase 1 Soluble Subunit Alpha 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 2977 ncbi.nlm.nih.gov/gene/2977 |
| Ensembl ID | ENSG00000152402 |
| UniProt ID | P33402 |
| OMIM ID | 139396 |
| HGNC ID | 4684 |
| Aliases | GC-SA2, GUC1A2, GUCA2, GUCY1A2 |
Description
GUCY1A2 encodes the alpha-2 subunit of soluble guanylyl cyclase (sGC), a heterodimeric enzyme that catalyzes the conversion of GTP to cyclic GMP (cGMP) upon activation by nitric oxide (NO). This subunit pairs with the beta-1 subunit (GUCY1B1) to form the functional NO receptor. sGC is a critical mediator of NO signaling in vascular smooth muscle, platelets, and neurons, regulating vasodilation, platelet aggregation, and neurotransmission.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypertension | Dysregulation of NO-sGC-cGMP pathway leads to impaired vasodilation and increased vascular tone. | OMIM #139396; NCBI Gene |
| Erectile Dysfunction | Reduced sGC activity impairs cGMP-mediated smooth muscle relaxation in corpus cavernosum. | OMIM #139396 |
| Pulmonary Hypertension | Altered sGC expression/activity contributes to pulmonary vascular remodeling. | NCBI Gene; UniProt P33402 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 2.4 | Not detected |
| Kidney | 4.7 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 18.3 | Neuroblastoma; high expression |
| HUVEC | 9.7 | Endothelial; moderate expression |
| A549 | 5.2 | Lung carcinoma; low expression |
| HEK293 | 3.1 | Embryonic kidney; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.172G>A (p.Gly58Arg) | Missense | <0.01% | Reduced sGC activity; associated with hypertension |
| c.1045C>T (p.Arg349Trp) | Missense | <0.01% | Impaired heme binding; loss of NO sensitivity |
| c.1472delC | Frameshift | <0.01% | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations that reduce or abolish sGC catalytic activity or heme binding, leading to impaired NO-cGMP signaling.
Gain of Function (GOF)
Not reported in literature or curated databases.
Dominant Negative (DN)
Not reported; sGC functions as a heterodimer, but dominant-negative effects have not been documented for GUCY1A2.
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)
Protein Summary
The GUCY1A2 protein (UniProt P33402) is a 762-amino acid alpha-2 subunit of soluble guanylyl cyclase. It contains a heme-binding domain and a catalytic domain. Upon NO binding to the heme moiety, the enzyme undergoes a conformational change that activates cGMP synthesis. The alpha-2/beta-1 heterodimer is the predominant form in human tissues. Post-translational modifications include phosphorylation, which modulates enzyme activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GUCY1A2 Knockout HEK293 Cell Line | EDJ-KQ1853 | Human | 2977 | Details Get a Quote |
| GUCY1A2 Knockout HeLa Cell Line | EDJ-KQ53456 | Human | 2977 | Details Get a Quote |
| GUCY1A2 Knockout A-549 Cell Line | EDJ-KQ61929 | Human | 2977 | Details Get a Quote |
| GUCY1A2 Knockout HCT 116 Cell Line | EDJ-KQ70410 | Human | 2977 | Details Get a Quote |
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