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

Unknown
Disease term	Disease name	Evidence	References	Source
Myocardial infarction	Myocardial Infarction		26343387	ClinVar
Myocardial Infarction	Myocardial Infarction			GWAS
Uterine Fibroids	Uterine Fibroids			GWAS
Coronary Heart Disease	Coronary Heart Disease			GWAS
Psoriasis	Psoriasis			GWAS
Parkinson disease	Parkinson disease			GWAS

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