GUCY2C (guanylate cyclase 2C)

Gene

• Entrez ID: 2984
• Gene name: Guanylate cyclase 2C
• Gene symbol: GUCY2C
• Synonyms (NCBI Gene): DIAR6, GC-C, GCC, GUC2C, HSER, MECIL, MUCIL, STAR
• Chromosome: 12
• Chromosome location: 12p12.3
• Summary: This gene encodes a transmembrane protein that functions as a receptor for endogenous peptides guanylin and uroguanylin, and the heat-stable E. coli enterotoxin. The encoded protein activates the cystic fibrosis transmembrane conductance regulator. Mutati

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1038451	hsa-miR-3163	CLIP-seq
MIRT1038452	hsa-miR-3646	CLIP-seq
MIRT1038453	hsa-miR-3977	CLIP-seq
MIRT1038454	hsa-miR-4668-3p	CLIP-seq
MIRT1038455	hsa-miR-544	CLIP-seq
MIRT1038455	hsa-miR-544	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
CDX2	Unknown	11684084

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0001653	Function	Peptide receptor activity	IBA
GO:0004383	Function	Guanylate cyclase activity	IBA
GO:0004383	Function	Guanylate cyclase activity	IDA	11950846
GO:0004383	Function	Guanylate cyclase activity	IEA
GO:0004383	Function	Guanylate cyclase activity	TAS	1680854
GO:0004672	Function	Protein kinase activity	IEA
GO:0005515	Function	Protein binding	IPI	11950846
GO:0005524	Function	ATP binding	IEA
GO:0005525	Function	GTP binding	IEA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006182	Process	CGMP biosynthetic process	IBA
GO:0006182	Process	CGMP biosynthetic process	IEA
GO:0007168	Process	Receptor guanylyl cyclase signaling pathway	IBA
GO:0007168	Process	Receptor guanylyl cyclase signaling pathway	TAS	1680854
GO:0009190	Process	Cyclic nucleotide biosynthetic process	IEA
GO:0009636	Process	Response to toxic substance	IEA
GO:0015643	Function	Toxic substance binding	IEA
GO:0016020	Component	Membrane	IEA
GO:0016829	Function	Lyase activity	IEA
GO:0016849	Function	Phosphorus-oxygen lyase activity	IEA
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0042127	Process	Regulation of cell population proliferation	IEA

Other IDs

• MIM: 601330
• HGNC: 4688
• e!Ensembl: ENSG00000070019

Protein

• UniProt ID: P25092
• Protein name: Guanylyl cyclase C (GC-C) (EC 4.6.1.2) (Heat-stable enterotoxin receptor) (STA receptor) (hSTAR) (Intestinal guanylate cyclase)
• Protein function: Guanylyl cyclase that catalyzes synthesis of cyclic GMP (cGMP) from GTP (PubMed:11950846, PubMed:1718270, PubMed:22436048, PubMed:22521417, PubMed:23269669). Receptor for the E.coli heat-stable enterotoxin; E.coli enterotoxin markedly stimulates
• PDB: 8FX4, 8GHO, 8GHP
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07714	PK_Tyr_Ser-Thr	499 → 745	Protein tyrosine and serine/threonine kinase	Domain
  PF00211	Guanylate_cyc	815 → 1002	Adenylate and Guanylate cyclase catalytic domain	Domain

• Sequence:

  MKTLLLDLALWSLLFQPGWLSFSSQVSQNCHNGSYEISVLMMGNSAFAEPLKNLEDAVNE
  GLEIVRGRLQNAGLNVTVNATFMYSDGLIHNSGDCRSSTCEGLDLLRKISNAQRMGCVLI
  GPSCTYSTFQMYLDTELSYPMISAGSFGLSCDYKETLTRLMSPARKLMYFLVNFWKTNDL
  PFKTYSWSTSYVYKNGTETEDCFWYLNALEASVSYFSHELGFKVVLRQDKEFQDILMDHN
  RKSNVIIMCGGPEFLYKLKGDRAVAEDIVIILVDLFNDQYFEDNVTAPDYMKNVLVLTLS
  PGNSLLNSSFSRNLSPTKRDFALAYLNGILLFGHMLKIFLENGENITTPKFAHAFRNLTF
  EGYDGPVTLDDWGDVDSTMVLLYTSVDTKKYKVLLTYDTHVNKTYPVDMSPTFTWKNSKL
  PNDITGRGPQILMIAVFTLTGAVVLLLLVALLMLRKYRKDYELRQKKWSHIPPENIFPLE
  TNETNHVSLKIDDDKRRDTIQRLRQCKYDKKRVILKDLKHNDGNFTEKQKIELNKLLQID
  YYNLTKFYGTVKLDTMIFGVIEYCERGSLREVLNDTISYPDGTFMDWEFKISVLYDIAKG
  MSYLHSSKTEVHGRLKSTNCVVDSRMVVKITDFGCNSILPPKKDLWTAPEHLRQANISQK
  GDVYSYGIIAQEIILRKETFYTLSCRDRNEKIFRVENSNGMKPFRPDLFLETAEEKELEV
  YLLVKNCWEEDPEKRPDFKKIETTLAKIFGLFHDQKNESYMDTLIRRLQLYSRNLEHLVE
  ERTQLYKAERDRADRLNFMLLPRLVVKSLKEKGFVEPELYEEVTIYFSDIVGFTTICKYS
  TPMEVVDMLNDIYKSFDHIVDHHDVYKVETIGDAYMVASGLPKRNGNRHAIDIAKMALEI
  LSFMGTFELEHLPGLPIWIRIGVHSGPCAAGVVGIKMPRYCLFGDTVNTASRMESTGLPL
  RIHVSGSTIAILKRTECQFLYEVRGETYLKGRGNETTYWLTGMKDQKFNLPTPPTVENQQ
  RLQAEFSDMIANSLQKRQAAGIRSQKPRRVASYKKGTLEYLQLNTTDKESTYF

• Sequence length: 1073

Pathways

KEGG:

Purine metabolism
Metabolic pathways
Hormone signaling

Reactome:

Digestion
Intestinal infectious diseases

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
Abnormal biliary tract morphology	Pathogenic	rs1057519441	RCV000416478	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Asplenia	Pathogenic	rs1057519441	RCV000416478	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Congenital diarrhea 6	Likely pathogenic; Pathogenic	rs2497633967, rs587776871, rs1947002584	RCV004017208 RCV000023094 RCV001197421	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Duodenal atresia	Pathogenic	rs1057519441	RCV000416478	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Meconium ileus	Pathogenic; Likely pathogenic	rs587784573, rs587776905, rs730880325, rs1451730099	RCV000148340 RCV000024308 RCV000024309 RCV001254596	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Reduced number of intrahepatic bile ducts	Pathogenic	rs1057519441	RCV000416478	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC INFANTILE DIARRHEA DUE TO GUANYLATE CYCLASE 2C OVERACTIVITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital secretory diarrhea, chloride type	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL SECRETORY DIARRHEA, SODIUM TYPE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL SODIUM DIARRHEA	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIARRHEA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DYSENTERY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GUCY2C-related disorder	Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency	Uncertain significance; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	12163327, 15754294, 16618413		★☆☆☆☆ Found in Text Mining only
Adenocarcinoma	Adenocarcinoma	LHGDN	12163327		★☆☆☆☆ Found in Text Mining only
Adenomatous Polyposis Coli	Multiple polyposis syndrome	BEFREE	20592492		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	31654574		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	31654574		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	Pubtator	25994218	Associate	★☆☆☆☆ Found in Text Mining only
Attention Deficit Disorder	Attention Deficit Hyperactivity Disorder	BEFREE	25064385		★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	BEFREE	25064385, 30953414		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	27903079, 30642983, 31010434		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	18566015, 34632925, 34954189	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	25304930	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinoma Medullary	Medullary carcinoma	Pubtator	19800103	Associate	★☆☆☆☆ Found in Text Mining only
Colitis	Colitis	BEFREE	22384056, 25979109		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	19620276, 20186008, 20498026, 21533822, 23387497, 24919572, 31010434		★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic neoplasm	Pubtator	8962140	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	10610624, 11579116, 14648708, 15754294, 16049286, 16336939, 16899600, 18785805, 19224751, 19450179, 19620276, 19895223, 20021465, 20592492, 21307149, 21618511, 21901559, 22038530, 22731908, 23375388, 23387497, 24085786, 27104761, 27903079, 28341670, 28895923, 28914772, 29210639, 29301746, 30131940, 30189250, 30642983, 30716341, 31010434, 9641495		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	CTD_human_DG	17155897		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	10206298, 10531324, 12594332, 16049286, 19224751, 19800103, 19895223, 21275338, 21702043, 21887684, 21901559, 25304930, 28504051, 34954189, 8962140	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal Neoplasms	Colorectal Neoplasms	LHGDN	14581363, 16899600		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal Neoplasms	Colorectal Neoplasms	CTD_human_DG	17155897		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	18566015	Inhibit	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal Neoplasms	Colorectal Neoplasms	BEFREE	19450179, 9641495		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital absence of spleen	Asplenia	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Congenital secretory diarrhea, sodium type (disorder)	Congenital secretory diarrhea	BEFREE	25994218, 26358773		★☆☆☆☆ Found in Text Mining only
Congenital secretory diarrhea, sodium type (disorder)	Congenital secretory diarrhea	ORPHANET_DG	25994218		★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn Disease	BEFREE	22436048, 28902124		★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Cystic Fibrosis	BEFREE	22521417, 28978796		★☆☆☆☆ Found in Text Mining only
Diarrhea	Diarrhea	Pubtator	22436048, 25994218, 34797252	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diarrhea 3 Secretory Sodium Congenital	Congenital secretory diarrhea	Pubtator	25994218, 26358773, 34797252	Associate	★☆☆☆☆ Found in Text Mining only
Duodenal atresia	Duodenal Atresia	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
EPILEPSY, PYRIDOXINE-DEPENDENT	Epilepsy	BEFREE	30189250		★☆☆☆☆ Found in Text Mining only
Esophagitis	Esotropia	Pubtator	22436048	Associate	★☆☆☆☆ Found in Text Mining only
Functional Gastrointestinal Disorders	Functional Gastrointestinal Disorders	BEFREE	29563144		★☆☆☆☆ Found in Text Mining only
Gastric Adenocarcinoma	Gastric Cancer	BEFREE	12163327		★☆☆☆☆ Found in Text Mining only
Gastrointestinal carcinoma	Gastrointestinal carcinoma	BEFREE	28494535		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Diseases	Gastrointestinal Diseases	BEFREE	24085786, 31611814		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Neoplasms	Gastrointestinal neoplasm	Pubtator	29261789, 36738333	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	30572911	Associate	★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	BEFREE	29615399		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory Bowel Disease	BEFREE	22384056, 25979109, 26835907, 28902124, 30353760		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory bowel disease	Pubtator	25994218, 32084423	Associate	★☆☆☆☆ Found in Text Mining only
Intestinal Neoplasms	Intestinal Neoplasms	BEFREE	19737566, 20592492, 22384056, 29210639		★☆☆☆☆ Found in Text Mining only
Intestinal Obstruction	Intestinal Obstruction	BEFREE	30782244		★☆☆☆☆ Found in Text Mining only
Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency	Intestinal Obstruction	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Irritable Bowel Syndrome	Irritable Bowel Syndrome	BEFREE	22069671, 29563144, 29784661, 29797376		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	19224751, 19800103	Associate	★☆☆☆☆ Found in Text Mining only
Malignant Carcinoid Syndrome	Carcinoid tumor of intestine	BEFREE	17687268		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of gastrointestinal tract	Malignant gastrointestinal tract tumors	BEFREE	29261789		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	29370189		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	19906106		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	15754294, 16899600, 19620276, 22038530, 22384056, 23375388, 25304930, 27765652, 28396341, 28494535, 28914772, 28916678, 29301746, 29615399, 30642983, 31010434		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	19620276, 20186008, 20498026, 21533822, 23387497, 24919572, 31010434		★☆☆☆☆ Found in Text Mining only
Meconium ileus	Meconium ileus	GENOMICS_ENGLAND_DG	22436048		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Meconium ileus	Meconium ileus	BEFREE	22521417, 25370039, 31079856		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Meconium ileus	Meconium ileus	UNIPROT_DG	22521417		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Meconium ileus	Meconium ileus	ORPHANET_DG	22521417		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Meconium ileus	Meconium ileus	CLINVAR_DG	25370039		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Meconium ileus	Meconium ileus	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Meconium ileus	Meconium ileus	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Metastatic melanoma	Metastatic Melanoma	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Microcolon	Microcolon	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	10610624, 12163327, 15754294, 16618413, 19737566, 20021465, 20592492, 21887684, 22731908, 23375388, 24085786, 25304930, 27104761, 28162021, 28418917, 28895923, 29370189, 30371057, 30716341		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	23375388, 28847213, 29112082		★☆☆☆☆ Found in Text Mining only
POPLITEAL PTERYGIUM SYNDROME, LETHAL TYPE	Bartsocas-Papas syndrome	BEFREE	29784661		★☆☆☆☆ Found in Text Mining only
Scleroderma Systemic	Systemic sclerosis	Pubtator	23237063	Associate	★☆☆☆☆ Found in Text Mining only
Secondary malignant neoplasm of colon and/or rectum	Colorectal Neoplasms	BEFREE	10711442, 11579116, 18785805, 21887684, 27903079, 28341670, 29615399, 9641495		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	19906106		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	21455338	Stimulate	★☆☆☆☆ Found in Text Mining only
Trichohepatoenteric Syndrome	Trichohepatoenteric syndrome	Pubtator	22436048	Associate	★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	25979109		★☆☆☆☆ Found in Text Mining only