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: 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 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]

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

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT440530	hsa-miR-412-3p	HITS-CLIP	24374217

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004383	Function	Guanylate cyclase activity	IDA	23505436
GO:0005515	Function	Protein binding	IPI	23505436
GO:0005525	Function	GTP binding	IEA
GO:0006182	Process	CGMP biosynthetic process	IDA	23505436
GO:0007263	Process	Nitric oxide mediated signal transduction	TAS	9742212
GO:0008015	Process	Blood circulation	TAS	9742212
GO:0008074	Component	Guanylate cyclase complex, soluble	IDA	23505436
GO:0008217	Process	Regulation of blood pressure	IEA
GO:0010750	Process	Positive regulation of nitric oxide mediated signal transduction	IEA
GO:0020037	Function	Heme binding	IEA
GO:0038023	Function	Signaling receptor activity	TAS	9742212
GO:0060087	Process	Relaxation of vascular associated smooth muscle	IEA
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
• 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

• 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
Disease name	Disease term	dbSNP ID	References
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	30104761, 22751097, 23202125, 29212778, 26343387, 28714975
Myocardial infarction	Myocardial Infarction	rs12316150, rs41303970, rs909253, rs7291467, rs2234693	26343387
Hypertension	Hypertensive disease	rs13306026	25249183, 18339647
Adenocarcinoma	Adenoid Cystic Carcinoma	rs121913530, rs886039394, rs121913474, rs-1	16762588
Moyamoya disease	Moyamoya disease 1	rs121434527, rs121434528, rs387906592, rs397514563, rs797045187, rs1555675538, rs1568149971, rs1599150380, rs-1, rs2079443410
Colonic neoplasms	Malignant tumor of colon, Colonic Neoplasms	rs267607789, rs774277300, rs781222233, rs1060502734, rs1060503333, rs1339238483	15059925
Moyamoya disease with achalasia	Moyamoya disease with early-onset achalasia	rs587777320, rs587777321, rs587777322, rs373182378, rs751701114, rs1368733883

Unknown
Disease name	Disease term	dbSNP ID	References
Achalasia	Esophageal Achalasia
Cardiovascular diseases	Cardiovascular Diseases		30595370
Coronary arteriosclerosis	Coronary Arteriosclerosis		22751097
Cutis marmorata	Cutis marmorata
Diabetic nephropathy	Diabetic Nephropathy		26305897
Dysphagia	Deglutition Disorders
Erectile dysfunction	Erectile dysfunction
High altitude pulmonary edema	High altitude pulmonary edema, High altitude pulmonary hypertension		25373139
Moyamoya disease with or without achalasia	MOYAMOYA DISEASE 6 WITH OR WITHOUT ACHALASIA		24581742, 26777256
Raynaud phenomenon	Raynaud Phenomenon
Salivary gland neoplasm	Salivary Gland Neoplasms		16762588
Malignant neoplasm of salivary gland	Malignant neoplasm of salivary gland		16762588
Stroke	Cerebrovascular accident