GUCY2C

guanylate cyclase 2C, the group of Transmembrane guanylate cyclases

Basic information

Region (hg38): 12:14612632-14696599

Previous symbols: [ "GUC2C" ]

Links

ENSG00000070019 ∙ NCBI:2984 ∙ OMIM:601330 ∙ HGNC:4688 ∙ Uniprot:P25092 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency (Definitive), mode of inheritance: AR
• congenital diarrhea 6 (Definitive), mode of inheritance: AD
• congenital diarrhea 6 (Strong), mode of inheritance: AD
• congenital diarrhea 6 (Limited), mode of inheritance: AR
• congenital sodium diarrhea (Supportive), mode of inheritance: AD
• congenital diarrhea 6 (Supportive), mode of inheritance: AD
• intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency (Supportive), mode of inheritance: AR
• congenital diarrhea 6 (Strong), mode of inheritance: AD
• intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diarrhea 6; Meconium ileus	AD/AR	Gastrointestinal; Renal	In Diarrhea 6, individuals may present in infancy with relatively severe dehydration, metabolic acidosis, and electrolyte disturbances, and preventive measures and early treatment may be beneficial; Awareness of sequelae that may require surgical interventions (eg, small bowel obstruction) may allow prompt recognition and treatment; Individuals may be at increased risk of urolithiasis, and preventive measures and prompt treatment may be beneficial; In Meconium ileus, individuals may present in infancy with relatively severe dehydration, metabolic acidosis, and electrolyte disturbances, and preventive measures and early treatment may be beneficial	Gastrointestinal; Renal	4006357; 22436048; 22436048; 22521417
Individuals with Meconium ileus have been described with features of Diarrhea 6 (in terms of chronic diarrhea in infancy)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GUCY2C gene.

• not_provided (741 variants)
• Inborn_genetic_diseases (124 variants)
• GUCY2C-related_disorder (23 variants)
• Congenital_diarrhea_6 (21 variants)
• Intestinal_obstruction_in_the_newborn_due_to_guanylate_cyclase_2C_deficiency (15 variants)
• Meconium_ileus (12 variants)
• not_specified (5 variants)
• Abnormal_biliary_tract_morphology (1 variants)
• Duodenal_atresia (1 variants)
• Congenital_secretory_diarrhea,_chloride_type (1 variants)
• Asplenia (1 variants)
• Reduced_number_of_intrahepatic_bile_ducts (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GUCY2C gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004963.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	129	9	143
missense	7	3	398	16	2	426
nonsense		3	19			22
start loss						0
frameshift	1	3	21			25
splice donor/acceptor (+/-2bp)			12			12
Total	8	9	455	145	11

Highest pathogenic variant AF is 0.000013111708

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GUCY2C	protein_coding	protein_coding	ENST00000261170	27	83944

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.39e-30	0.00168	125583	0	165	125748	0.000656

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.25	500	585	0.855	0.0000308	7096
Missense in Polyphen		159	231.13	0.68793		2778
Synonymous	1.49	185	213	0.870	0.0000116	1964
Loss of Function	1.04	51	59.7	0.854	0.00000322	720

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00208	0.00208
Ashkenazi Jewish	0.00	0.00
East Asian	0.000495	0.000489
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000751	0.000739
Middle Eastern	0.000495	0.000489
South Asian	0.000627	0.000621
Other	0.000492	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for the E.coli heat-stable enterotoxin (E.coli enterotoxin markedly stimulates the accumulation of cGMP in mammalian cells expressing GC-C). Also activated by the endogenous peptides guanylin and uroguanylin.
• Disease: DISEASE: Diarrhea 6 (DIAR6) [MIM:614616]: A relatively mild, early-onset chronic diarrhea that may be associated with increased susceptibility to inflammatory bowel disease, small bowel obstruction, and esophagitis. {ECO:0000269|PubMed:22436048}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Meconium ileus (MECIL) [MIM:614665]: A condition characterized by a intestinal obstruction due to inspissated meconium in the distal ileum and cecum, which develops in utero and presents shortly after birth as a failure to pass meconium. Meconium ileus is a known clinical manifestation of cystic fibrosis. {ECO:0000269|PubMed:22521417}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Purine metabolism - Homo sapiens (human);Disease;Intestinal infectious diseases;Uptake and actions of bacterial toxins;Infectious disease;Purine metabolism;actions of nitric oxide in the heart;Purine nucleotides nucleosides metabolism;Digestion;Digestion and absorption (Consensus)

Recessive Scores

• pRec: 0.153

Intolerance Scores

• loftool: 0.374
• rvis_EVS: -1.1
• rvis_percentile_EVS: 6.89

Haploinsufficiency Scores

• pHI: 0.438
• hipred: N
• hipred_score: 0.441
• ghis: 0.432

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.873

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gucy2c
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; homeostasis/metabolism phenotype; immune system phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: cGMP biosynthetic process;protein phosphorylation;signal transduction;receptor guanylyl cyclase signaling pathway;digestion;response to toxic substance;intracellular signal transduction;regulation of cell population proliferation
• Cellular component: endoplasmic reticulum membrane;plasma membrane;integral component of membrane
• Molecular function: peptide receptor activity;guanylate cyclase activity;protein kinase activity;protein binding;ATP binding;GTP binding;toxic substance binding