Soluble guanylate cyclases are heterodimeric proteins that catalyze the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. The protein encoded by this gene is an alpha subunit of this complex and it interacts with a beta subunit to form the guanylate cyclase enzyme, which is activated by nitric oxide. Several transcript variants encoding a few different isoforms have been... See more...

Aliases for GUCY1A1 Gene

Aliases for GUCY1A1 Gene

  • Guanylate Cyclase 1 Soluble Subunit Alpha 1 2 3 5
  • Guanylate Cyclase Soluble Subunit Alpha-1 3 4
  • Soluble Guanylate Cyclase Large Subunit 3 4
  • Guanylate Cyclase 1, Soluble, Alpha 3 2 3
  • GCS-Alpha-3 3 4
  • EC 4 52
  • GUCY1A3 3 4
  • GUC1A3 3 4
  • GUCSA3 3 4
  • Guanylate Cyclase Soluble Subunit Alpha-3 4
  • Guanylate Cyclase 1 Soluble Subunit Alpha 2
  • GC-S-Alpha-1 3
  • GCS-Alpha-1 4
  • GC-SA3 3
  • GUCA3 3
  • MYMY6 3

External Ids for GUCY1A1 Gene

Previous HGNC Symbols for GUCY1A1 Gene

  • GUC1A3
  • GUCY1A3

Summaries for GUCY1A1 Gene

Entrez Gene Summary for GUCY1A1 Gene

  • Soluble guanylate cyclases are heterodimeric proteins that catalyze the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. The protein encoded by this gene is an alpha subunit of this complex and it interacts with a beta subunit to form the guanylate cyclase enzyme, which is activated by nitric oxide. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

GeneCards Summary for GUCY1A1 Gene

GUCY1A1 (Guanylate Cyclase 1 Soluble Subunit Alpha 1) is a Protein Coding gene. Diseases associated with GUCY1A1 include Moyamoya Disease 6 With Or Without Achalasia and Moyamoya Disease 1. Among its related pathways are Oxytocin signaling pathway and Sweet Taste Signaling. An important paralog of this gene is GUCY1A2.

Gene Wiki entry for GUCY1A1 Gene

Additional gene information for GUCY1A1 Gene

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GUCY1A1 Gene

Genomics for GUCY1A1 Gene

GeneHancer (GH) Regulatory Elements for GUCY1A1 Gene

Promoters and enhancers for GUCY1A1 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J155666 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 500.7 +1.4 1433 3.6 EP300 USF1 ZIC2 ZBTB26 TRIM22 POLR2A OSR2 ZBTB17 ZNF263 MXI1 GUCY1A1 HSALNG0038022
GH04J155665 Enhancer 0.4 Ensembl dbSUPER 500.7 -0.9 -867 0.6 EZH2 GUCY1A1 piR-61945-395
GH04J155614 Enhancer 0.6 Ensembl 15.6 -51.2 -51167 1.2 TRIM22 NBN BMI1 TBP NFATC3 TBX21 ATF7 SMAD1 TARDBP IKZF1 GUCY1A1 piR-61945-395 HSALNG0038032
GH04J155637 Enhancer 0.7 ENCODE 12.5 -27.6 -27639 3 ZNF384 ARNT MEF2B MAFK SMARCA5 IKZF1 NFATC3 HDGF TBX21 ZNF217 GUCY1A1 piR-61945-395
GH04J155706 Enhancer 0.6 Ensembl 11.9 +39.3 39332 0.6 ZSCAN5C TRIM28 OSR2 NR2F2 IKZF3 ZNF843 ZNF18 CTBP1 PKNOX1 FOXA1 GUCY1A1 GUCY1B1 lnc-ASIC5-2 HSALNG0038022
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GUCY1A1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GUCY1A1

Genomic Locations for GUCY1A1 Gene

Genomic Locations for GUCY1A1 Gene
70,495 bases
Plus strand
70,353 bases
Plus strand

Genomic View for GUCY1A1 Gene

Genes around GUCY1A1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GUCY1A1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GUCY1A1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GUCY1A1 Gene

Proteins for GUCY1A1 Gene

  • Protein details for GUCY1A1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Guanylate cyclase soluble subunit alpha-1
    Protein Accession:
    Secondary Accessions:
    • D3DP19
    • D6RDW3
    • O43843
    • Q8TAH3

    Protein attributes for GUCY1A1 Gene

    690 amino acids
    Molecular mass:
    77452 Da
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
    Quaternary structure:
    • The active enzyme is formed by a heterodimer of an alpha and a beta subunit. Heterodimer with GUCY1B1 (PubMed:9742212, PubMed:23505436, PubMed:24669844).
    • There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms.
    • Sequence=CAA47145.1; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for GUCY1A1 Gene

    Alternative splice isoforms for GUCY1A1 Gene


neXtProt entry for GUCY1A1 Gene

Selected DME Specific Peptides for GUCY1A1 Gene


Post-translational modifications for GUCY1A1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for GUCY1A1 Gene

Gene Families for GUCY1A1 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for GUCY1A1 Gene

GenScript: Design optimal peptide antigens:
  • Soluble guanylate cyclase large subunit (GCYA3_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
  • Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
genes like me logo Genes that share domains with GUCY1A1: view

Function for GUCY1A1 Gene

Molecular function for GUCY1A1 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=GTP = 3',5'-cyclic GMP + diphosphate; Xref=Rhea:RHEA:13665, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:57746; EC=; Evidence={ECO:0000269 PubMed:23505436, ECO:0000269 PubMed:24669844, ECO:0000269 PubMed:9742212};.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by nitric oxide in the presence of magnesium or manganese ions.

Enzyme Numbers (IUBMB) for GUCY1A1 Gene

Phenotypes From GWAS Catalog for GUCY1A1 Gene

Gene Ontology (GO) - Molecular Function for GUCY1A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004383 guanylate cyclase activity TAS,IDA 23505436
GO:0005515 protein binding IPI 23505436
GO:0005525 GTP binding IEA --
GO:0016829 lyase activity IEA --
GO:0016849 phosphorus-oxygen lyase activity IEA --
genes like me logo Genes that share ontologies with GUCY1A1: view
genes like me logo Genes that share phenotypes with GUCY1A1: view

Human Phenotype Ontology for GUCY1A1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for GUCY1A1 Gene

MGI Knock Outs for GUCY1A1:

Animal Model Products

miRNA for GUCY1A1 Gene

miRTarBase miRNAs that target GUCY1A1

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for GUCY1A1 Gene

Localization for GUCY1A1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GUCY1A1 Gene


Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GUCY1A1 gene
Compartment Confidence
cytosol 5
nucleus 2
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GUCY1A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0008074 guanylate cyclase complex, soluble IDA 23505436
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0098978 glutamatergic synapse IEA --
genes like me logo Genes that share ontologies with GUCY1A1: view

Pathways & Interactions for GUCY1A1 Gene

PathCards logo

SuperPathways for GUCY1A1 Gene

SuperPathway Contained pathways
1 G-Beta Gamma Signaling
2 Oxytocin signaling pathway
3 Sweet Taste Signaling
4 cGMP-PKG signaling pathway
5 Circadian entrainment
genes like me logo Genes that share pathways with GUCY1A1: view

Pathways by source for GUCY1A1 Gene

2 GeneGo (Thomson Reuters) pathways for GUCY1A1 Gene
  • Apoptosis and survival_Anti-apoptotic action of nuclear ESR1 and ESR2
  • Development EDNRB signaling
10 Qiagen pathways for GUCY1A1 Gene
  • Cellular Effects of Sildenafil
  • CRHR Pathway
  • Dopamine-DARPP32 Feedback onto cAMP Pathway
  • eNOS Signaling
  • Intracellular Calcium Signaling

Gene Ontology (GO) - Biological Process for GUCY1A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006182 cGMP biosynthetic process IEA,IDA 23505436
GO:0007263 nitric oxide mediated signal transduction TAS 9742212
GO:0008015 blood circulation TAS 9742212
GO:0008217 regulation of blood pressure IEA --
GO:0009190 cyclic nucleotide biosynthetic process IEA --
genes like me logo Genes that share ontologies with GUCY1A1: view

No data available for SIGNOR curated interactions for GUCY1A1 Gene

Drugs & Compounds for GUCY1A1 Gene

(14) Drugs for GUCY1A1 Gene - From: ApexBio, DGIdb, HMDB, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Riociguat Approved Pharma Soluble guanylate cyclase (sGC) stimulator 48
Magnesium Approved, Experimental, Investigational Pharma 0
Phosphoric acid Approved Pharma 0
Manganese Approved Nutra 51
Cyclic GMP Experimental Pharma 0

(1) Additional Compounds for GUCY1A1 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • [(ho)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • PYROphosphATE

(5) Tocris Compounds for GUCY1A1 Gene

Compound Action Cas Number
A 350619 hydrochloride Soluble guanylyl cyclase (sGC) activator 1217201-17-6
BAY 41-2272 Soluble guanylyl cyclase (sGC) activator 256376-24-6
BPIPP Non-competitive GC inhibitor. Also AC inhibitor 325746-94-9
CFM 1571 hydrochloride Soluble guanylyl cyclase (sGC) activator 1215548-30-3
YC 1 Soluble guanylyl cyclase (sGC) activator; induces G1 cell cycle arrest 170632-47-0

(8) ApexBio Compounds for GUCY1A1 Gene

Compound Action Cas Number
A 350619 hydrochloride Activator of soluble guanylyl cyclase (sGC) 1217201-17-6
BAY 41-2272 Activator of soluble guanylyl cyclase (sGC) 256376-24-6
BPIPP 325746-94-9
CFM 1571 hydrochloride sGC activator 1215548-30-3
Cinaciguat Soluble guanylate cyclase (sGC) activators 329773-35-5
Guanylin (human) 183200-12-6
NS 2028 204326-43-2
Riociguat Soluble guanylate cyclase (sGC) stimulator 625115-55-1
genes like me logo Genes that share compounds with GUCY1A1: view

Drug Products

Transcripts for GUCY1A1 Gene

mRNA/cDNA for GUCY1A1 Gene

18 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for GUCY1A1 Gene

No ASD Table

Relevant External Links for GUCY1A1 Gene

GeneLoc Exon Structure for

Expression for GUCY1A1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GUCY1A1

mRNA Expression by UniProt/SwissProt for GUCY1A1 Gene:

Tissue specificity: Detected in brain cortex and lung (at protein level).

Evidence on tissue expression from TISSUES for GUCY1A1 Gene

  • Nervous system(4.9)
  • Kidney(4.4)
  • Eye(2.2)
  • Heart(2)
  • Lung(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for GUCY1A1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • digestive
  • reproductive
Head and neck:
  • head
  • mouth
  • pharynx
  • esophagus
  • stomach
  • penis

No data available for mRNA expression in normal human tissues , mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for GUCY1A1 Gene

Orthologs for GUCY1A1 Gene

This gene was present in the common ancestor of animals.

Orthologs for GUCY1A1 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia GUCY1A3 31 30
  • 99.66 (n)
(Canis familiaris)
Mammalia GUCY1A3 31 30
  • 89.61 (n)
(Ornithorhynchus anatinus)
Mammalia GUCY1A3 31
  • 88 (a)
(Monodelphis domestica)
Mammalia GUCY1A3 31
  • 87 (a)
(Bos Taurus)
Mammalia GUCY1A1 31
  • 86 (a)
GUCY1A3 30
  • 83.19 (n)
(Mus musculus)
Mammalia Gucy1a3 31 30
  • 84.2 (n)
Gucy1a1 17
(Rattus norvegicus)
Mammalia Gucy1a3 30
  • 84.18 (n)
(Gallus gallus)
Aves GUCY1A3 31 30
  • 78.29 (n)
(Anolis carolinensis)
Reptilia GUCY1A3 31
  • 83 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia gucy1a3 30
  • 72.93 (n)
(Danio rerio)
Actinopterygii gucy1a3 31 30
  • 54.78 (n)
Dr.12554 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.6530 30
fruit fly
(Drosophila melanogaster)
Insecta Gycalpha99B 31
  • 35 (a)
(Caenorhabditis elegans)
Secernentea gcy-29 31
  • 13 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 43 (a)
Species where no ortholog for GUCY1A1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GUCY1A1 Gene

Gene Tree for GUCY1A1 (if available)
Gene Tree for GUCY1A1 (if available)
Evolutionary constrained regions (ECRs) for GUCY1A1: view image

Paralogs for GUCY1A1 Gene

genes like me logo Genes that share paralogs with GUCY1A1: view

Variants for GUCY1A1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GUCY1A1 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
711123 Likely Benign: not provided 155,710,987(+) G/A SYNONYMOUS_VARIANT
715600 Benign: not provided 155,696,940(+) G/A MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT
721688 Likely Benign: not provided 155,710,555(+) G/A SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT
727091 Likely Benign: not provided 155,696,879(+) G/A SYNONYMOUS_VARIANT,INTRON_VARIANT
732167 Likely Benign: not provided 155,722,184(+) A/G SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for GUCY1A1 Gene

Structural Variations from Database of Genomic Variants (DGV) for GUCY1A1 Gene

Variant ID Type Subtype PubMed ID
esv23465 CNV loss 19812545
esv2421932 CNV deletion 20811451
esv2514554 CNV deletion 19546169
esv2674234 CNV deletion 23128226
esv275314 CNV loss 21479260
esv2759290 CNV loss 17122850
esv2760878 CNV loss 21179565
esv3602765 CNV loss 21293372
esv3602766 CNV loss 21293372
esv3894054 CNV loss 25118596
nsv1022201 CNV loss 25217958
nsv1073383 CNV deletion 25765185
nsv1130925 CNV deletion 24896259
nsv1150507 CNV deletion 26484159
nsv437445 CNV loss 16327808
nsv442925 CNV loss 18776908
nsv4563 CNV insertion 18451855
nsv509940 OTHER sequence alteration 20534489
nsv514260 CNV loss 21397061
nsv519870 CNV loss 19592680

Variation tolerance for GUCY1A1 Gene

Residual Variation Intolerance Score: 25.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.05; 50.50% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GUCY1A1 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GUCY1A1 Gene

Disorders for GUCY1A1 Gene

MalaCards: The human disease database

(6) MalaCards diseases for GUCY1A1 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
moyamoya disease 6 with or without achalasia
  • mymy6
moyamoya disease 1
  • mymy1
myocardial infarction
  • myocardial infarction, susceptibility to
  • achalasia of cardia
  • infantile hemiplegia
- elite association - COSMIC cancer census association via MalaCards


  • Moyamoya disease 6 with or without achalasia (MYMY6) [MIM:615750]: A form of Moyamoya disease, a progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults. MYMY6 is characterized by severe cerebral angiopathy and onset of severe achalasia in infancy or early childhood. {ECO:0000269 PubMed:24581742}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for GUCY1A1

genes like me logo Genes that share disorders with GUCY1A1: view

No data available for Genatlas for GUCY1A1 Gene

Publications for GUCY1A1 Gene

  1. Molecular cloning of the cDNAs coding for the two subunits of soluble guanylyl cyclase from human brain. (PMID: 1352257) Giuili G … Guellaën G (FEBS letters 1992) 2 3 4 54
  2. Loss of α1β1 soluble guanylate cyclase, the major nitric oxide receptor, leads to moyamoya and achalasia. (PMID: 24581742) Hervé D … Tournier-Lasserve E (American journal of human genetics 2014) 3 4 54
  3. Crystal structures of the catalytic domain of human soluble guanylate cyclase. (PMID: 23505436) Allerston CK … Gileadi O (PloS one 2013) 3 4 54
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 54
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 54

Products for GUCY1A1 Gene

Sources for GUCY1A1 Gene