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

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Moyamoya disease 1	Pathogenic	rs373182378, rs751701114	RCV000755172 RCV000755174
Moyamoya disease with early-onset achalasia	Likely pathogenic; Pathogenic	rs587777320, rs587777321, rs587777322, rs1347958848, rs373182378, rs751701114, rs1368733883	RCV001783406 RCV000114952 RCV000114953 RCV000114954 RCV003108001 RCV000677373 RCV000677374 RCV000677376
Myocardial infarction, susceptibility to, 1	Pathogenic	rs587777928	RCV000077777

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
GUCY1A1-related disorder	Benign	rs61736997	RCV003903413
See cases	Conflicting classifications of pathogenicity	rs781020381	RCV002252210
Thyroid cancer, nonmedullary, 1	Benign	rs2306554	RCV005921028

Associations from Text Mining
Disease Name	Relationship Type	References
Atherosclerosis	Inhibit	28487391
Atherosclerosis	Associate	31883534
Cardiovascular Diseases	Associate	31228190
Colonic Neoplasms	Associate	38179743
Coronary Artery Disease	Associate	28487391, 31228190, 31883534, 35192625
Coronary Disease	Associate	28982690
Esophageal Achalasia	Associate	24581742, 30001348
Infarction Anterior Cerebral Artery	Associate	31883534
Intracranial Arteriosclerosis	Associate	31883534
Moyamoya Disease	Associate	24581742, 30001348, 36941667
Neoplasms	Associate	36981021
Parkinson Disease	Associate	28586827
Pulmonary Arterial Hypertension	Associate	36941667
Stomach Neoplasms	Associate	36981021
Superior Mesenteric Artery Syndrome	Associate	36941667