GUCY1A1 (guanylate cyclase 1 soluble subunit alpha 1)

Gene

• Entrez ID: 2982
• Gene name: Guanylate cyclase 1 soluble subunit alpha 1
• Gene symbol: GUCY1A1
• Synonyms (NCBI Gene): GC-S-alpha-1, GC-SA3, GCS-alpha-3, GUC1A3, GUCA3, GUCSA3, GUCY1A3, MYMY6
• Chromosome: 4
• Chromosome location: 4q32.1
• Summary: 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 guanylat

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs373182378	C>T	Pathogenic	Coding sequence variant, stop gained
rs587777320	G>A,T	Pathogenic	Splice donor variant
rs587777321	C>T	Pathogenic	Stop gained, coding sequence variant
rs587777322	A>-	Pathogenic	Frameshift variant, coding sequence variant
rs587777928	->T	Pathogenic	Frameshift variant, coding sequence variant, 5 prime UTR variant
rs751701114	G>A	Pathogenic	Missense variant, coding sequence variant
rs781020381	GA>-	Pathogenic	Frameshift variant, coding sequence variant, 5 prime UTR variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004383	Function	Guanylate cyclase activity	IBA
GO:0004383	Function	Guanylate cyclase activity	IDA	23505436
GO:0004383	Function	Guanylate cyclase activity	IEA
GO:0004383	Function	Guanylate cyclase activity	TAS	9742212
GO:0005515	Function	Protein binding	IPI	23505436, 31514202, 33961781
GO:0005525	Function	GTP binding	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006182	Process	CGMP biosynthetic process	IBA
GO:0006182	Process	CGMP biosynthetic process	IDA	23505436
GO:0006182	Process	CGMP biosynthetic process	IEA
GO:0006182	Process	CGMP biosynthetic process	IEA
GO:0007263	Process	Nitric oxide mediated signal transduction	IEA
GO:0007263	Process	Nitric oxide mediated signal transduction	TAS	9742212
GO:0008015	Process	Blood circulation	TAS	9742212
GO:0008074	Component	Guanylate cyclase complex, soluble	IBA
GO:0008074	Component	Guanylate cyclase complex, soluble	IDA	23505436
GO:0008074	Component	Guanylate cyclase complex, soluble	IPI	23505436
GO:0008074	Component	Guanylate cyclase complex, soluble	TAS	1352257
GO:0008217	Process	Regulation of blood pressure	IEA
GO:0009190	Process	Cyclic nucleotide biosynthetic process	IEA
GO:0010750	Process	Positive regulation of nitric oxide mediated signal transduction	IEA
GO:0016829	Function	Lyase activity	IEA
GO:0016849	Function	Phosphorus-oxygen lyase activity	IEA
GO:0019934	Process	CGMP-mediated signaling	IBA
GO:0020037	Function	Heme binding	IEA
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0038023	Function	Signaling receptor activity	TAS	9742212
GO:0038060	Process	Nitric oxide-cGMP-mediated signaling	IDA	23505436
GO:0060087	Process	Relaxation of vascular associated smooth muscle	IEA
GO:0070482	Process	Response to oxygen levels	IBA
GO:0098925	Process	Retrograde trans-synaptic signaling by nitric oxide, modulating synaptic transmission	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0098982	Component	GABA-ergic synapse	IEA

Other IDs

• MIM: 139396
• HGNC: 4685
• e!Ensembl: ENSG00000164116

Protein

• UniProt ID: Q02108
• Protein name: Guanylate cyclase soluble subunit alpha-1 (GCS-alpha-1) (EC 4.6.1.2) (Guanylate cyclase soluble subunit alpha-3) (GCS-alpha-3) (Soluble guanylate cyclase large subunit)
• PDB: 3UVJ, 4NI2, 6JT0, 6JT1, 6JT2, 7D9R, 7D9S, 7D9T, 7D9U, 8HBE, 8HBF, 8HBH
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07700	HNOB	71 → 235	Haem-NO-binding	Domain
  PF07701	HNOBA	275 → 362	Heme NO binding associated	Domain
  PF07701	HNOBA	351 → 466	Heme NO binding associated	Domain
  PF00211	Guanylate_cyc	472 → 658	Adenylate and Guanylate cyclase catalytic domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Detected in brain cortex and lung (at protein level). {ECO:0000269|PubMed:1352257}.
• Sequence:

  MFCTKLKDLKITGECPFSLLAPGQVPNESSEEAAGSSESCKATVPICQDIPEKNIQESLP
  QRKTSRSRVYLHTLAESICKLIFPEFERLNVALQRTLAKHKIKESRKSLEREDFEKTIAE
  QAVAAGVPVEVIKESLGEEVFKICYEEDENILGVVGGTLKDFLNSFSTLLKQSSHCQEAG
  KRGRLEDASILCLDKEDDFLHVYYFFPKRTTSLILPGIIKAAAHVLYETEVEVSLMPPCF
  HNDCSEFVNQPYLLYSVHMKSTKPSLSPSKPQSSLVIPTSLFCKTFPFHFMFDKDMTILQ
  FGNGIRRLMNRRDFQGKPNFEEYFEILTPKINQTFSGIMTMLNMQFVVRVRRWDNSVKKS
  SRVMDLKGQMIYIVESSAILFLGSPCVDRLEDFTGRGLYLSDIPIHNALRDVVLIGEQAR
  AQDGLKKRLGKLKATLEQAHQALEEEKKKTVDLLCSIFPCEVAQQLWQGQVVQAKKFSNV
  TMLFSDIVGFTAICSQCSPLQVITMLNALYTRFDQQCGELDVYKVETIGDAYCVAGGLHK
  ESDTHAVQIALMALKMMELSDEVMSPHGEPIKMRIGLHSGSVFAGVVGVKMPRYCLFGNN
  VTLANKFESCSVPRKINVSPTTYRLLKDCPGFVFTPRSREELPPNFPSEIPGICHFLDAY
  QQGTNSKPCFQKKDVEDGNANFLGKASGID

• Sequence length: 690

Pathways

KEGG:

Purine metabolism
Metabolic pathways
cGMP-PKG signaling pathway
Vascular smooth muscle contraction
Gap junction
Platelet activation
Circadian entrainment
Long-term depression
Oxytocin signaling pathway
Renin secretion
Salivary secretion

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Moyamoya disease 1	Pathogenic	rs373182378, rs751701114	RCV000755172 RCV000755174	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Moyamoya disease with early-onset achalasia	Likely pathogenic; Pathogenic	rs587777320, rs587777321, rs587777322, rs1347958848, rs373182378, rs751701114, rs1368733883	RCV001783406 RCV000114952 RCV000114953 RCV000114954 RCV003108001 RCV000677373 RCV000677374 RCV000677376	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Myocardial infarction, susceptibility to, 1	Pathogenic	rs587777928	RCV000077777	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CARCINOMA, ADENOID CYSTIC	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOVASCULAR DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC ISCHEMIC HEART DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLONIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERIOSCLEROSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	CTD, GWAS catalog CTD, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ATHEROSCLEROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY HEART DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC NEPHROPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ESSENTIAL HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GUCY1A1-related disorder	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	CTD, GWAS catalog CTD, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSIVE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOYAMOYA DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOYAMOYA DISEASE 6 WITH ACHALASIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOYAMOYA DISEASE 6 WITH OR WITHOUT ACHALASIA	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOYAMOYA DISEASE WITH EARLY ONSET ACHALASIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL ISCHEMIA	—	Disgenet, GWAS catalog Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSON DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSORIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PULMONARY EDEMA OF MOUNTAINEERS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SALIVARY GLAND NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THROMBOSIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UTERINE FIBROID	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenoid Cystic Carcinoma	Adenocarcinoma	CTD_human_DG	16762588		★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	27315776, 27342234		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	27315776, 27342234		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	Pubtator	28487391	Inhibit	★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	Pubtator	31883534	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	GWASCAT_DG	30595370		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	31228190		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular disease	Pubtator	31228190	Associate	★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	31228190		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic Neoplasms	CTD_human_DG	15059925		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colonic Neoplasms	Colonic neoplasm	Pubtator	38179743	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Arteriosclerosis	Coronary Arteriosclerosis	CTD_human_DG	22751097		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Arteriosclerosis	Coronary Arteriosclerosis	BEFREE	27315776, 27342234, 30768153, 31228190		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease	Coronary artery disease	CTD_human_DG	22751097		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease	Coronary artery disease	GWASDB_DG	23202125		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease	Coronary artery disease	GWASCAT_DG	26343387, 28714975, 29212778, 30104761		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease	Coronary artery disease	BEFREE	27315776, 27342234, 29601927, 30768153, 31228190		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease	Coronary artery disease	Pubtator	28487391, 31228190, 31883534, 35192625	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Disease	Coronary artery disease	Pubtator	28982690	Associate	★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	27315776, 27342234, 30768153, 31228190		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cutis marmorata	Cutis marmorata	HPO_DG			★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathy	Diabetic Nephropathy	GWASCAT_DG	26305897		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Erectile dysfunction	Erectile Dysfunction	HPO_DG			★☆☆☆☆ Found in Text Mining only
Esophageal Achalasia	Esophageal achalasia	Pubtator	24581742, 30001348	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal Achalasia	Achalasia	BEFREE	26777256, 30001348		★☆☆☆☆ Found in Text Mining only
Esophageal Achalasia	Achalasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	15201957		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	LHGDN	15201957		★☆☆☆☆ Found in Text Mining only
High altitude pulmonary edema	High Altitude Pulmonary Edema	CTD_human_DG	25373139		★☆☆☆☆ Found in Text Mining only
High altitude pulmonary hypertension	High altitude pulmonary edema	CTD_human_DG	25373139		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	CTD_human_DG	18339647		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	GWASCAT_DG	25249183		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	BEFREE	25373139, 26777256, 28465505		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant neoplasm of salivary gland	Malignant neoplasm of salivary gland	CTD_human_DG	16762588		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	CTD_human_DG	15059925		★☆☆☆☆ Found in Text Mining only
Moyamoya Disease	Moyamoya Disease	BEFREE	24581742, 26777256, 27128593, 30001348		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Moyamoya Disease	Moyamoya disease	Pubtator	24581742, 30001348, 36941667	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Moyamoya disease 1	Moyamoya disease	BEFREE	26777256, 27128593		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Moyamoya disease 1	Moyamoya disease	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MOYAMOYA DISEASE 6 WITH OR WITHOUT ACHALASIA	MOYAMOYA DISEASE WITH OR WITHOUT ACHALASIA	ORPHANET_DG	24581742		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOYAMOYA DISEASE 6 WITH OR WITHOUT ACHALASIA	MOYAMOYA DISEASE WITH OR WITHOUT ACHALASIA	GENOMICS_ENGLAND_DG	26777256		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOYAMOYA DISEASE 6 WITH OR WITHOUT ACHALASIA	MOYAMOYA DISEASE WITH OR WITHOUT ACHALASIA	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOYAMOYA DISEASE 6 WITH OR WITHOUT ACHALASIA	MOYAMOYA DISEASE WITH OR WITHOUT ACHALASIA	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Moyamoya disease with early-onset achalasia	Moyamoya Disease With Achalasia	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Myocardial Infarction	Myocardial Infarction	GWASCAT_DG	26343387		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myocardial Infarction	Myocardial Infarction	BEFREE	27315776, 31228190		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinson Disease	Parkinson disease	Pubtator	28586827	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pulmonary Arterial Hypertension	Pulmonary arterial hypertension	Pubtator	36941667	Associate	★☆☆☆☆ Found in Text Mining only
Raynaud Phenomenon	Raynaud Phenomenon	HPO_DG			★☆☆☆☆ Found in Text Mining only
Salivary Gland Neoplasms	Salivary gland neoplasm	CTD_human_DG	16762588		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Stomach Neoplasms	Stomach neoplasms	Pubtator	36981021	Associate	★☆☆☆☆ Found in Text Mining only