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GUCY2C guanylate cyclase 2C [ Homo sapiens (human) ]

Gene ID: 2984, updated on 14-Nov-2024

Summary

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Official Symbol
GUCY2Cprovided by HGNC
Official Full Name
guanylate cyclase 2Cprovided by HGNC
Primary source
HGNC:HGNC:4688
See related
Ensembl:ENSG00000070019 MIM:601330; AllianceGenome:HGNC:4688
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
GCC; GC-C; HSER; STAR; DIAR6; GUC2C; MECIL; MUCIL
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. Mutations in this gene are associated with familial diarrhea (autosomal dominant) and meconium ileus (autosomal recessive). [provided by RefSeq, Nov 2016]
Expression
Biased expression in duodenum (RPKM 36.3), small intestine (RPKM 36.1) and 2 other tissues See more
Orthologs
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Genomic context

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See GUCY2C in Genome Data Viewer
Location:
12p12.3
Exon count:
27
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (14612632..14696599, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (14490079..14574057, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (14765566..14849533, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene phospholipase B domain containing 1 Neighboring gene uncharacterized LOC101928317 Neighboring gene RN7SK pseudogene 134 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:14719662-14719838 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:14720083-14720764 Neighboring gene PLBD1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6047 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6048 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6049 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4275 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6050 Neighboring gene GUCY2C antisense RNA 1 Neighboring gene MPRA-validated peak1579 silencer Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:14857936-14858468 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:14858469-14859000 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:14862728-14863259 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:14863260-14863792 Neighboring gene Sharpr-MPRA regulatory region 453 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6051 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:14881606-14881786 Neighboring gene uncharacterized LOC105369669 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:14922691-14923286 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:14923287-14923883 Neighboring gene H4 histone 16

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. A validated quantitative assay to detect occult micrometastases by reverse transcriptase-polymerase chain reaction of guanylyl cyclase C in patients with colorectal cancer. Schulz S, et al. Clin Cancer Res, 2006 Aug 1. PMID 16899600
  2. Meconium ileus in a Lebanese family secondary to mutations in the GUCY2C gene. Smith A, et al. Eur J Hum Genet, 2015 Jul. PMID 25370039, Free PMC Article
  3. Association between GUC2C and ADHD: evidence from both categorical and quantitative traits. Liu L, et al. Psychiatry Res, 2014 Dec 15. PMID 25064385
  4. Molecular testing for lymph node metastases as a determinant of colon cancer recurrence: results from a retrospective multicenter study. Sargent DJ, et al. Clin Cancer Res, 2014 Aug 15. PMID 24919572
  5. Meconium ileus caused by mutations in GUCY2C, encoding the CFTR-activating guanylate cyclase 2C. Romi H, et al. Am J Hum Genet, 2012 May 4. PMID 22521417, Free PMC Article

See all (64) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Molecular insights into recognition of GUCY2C by T-cell engaging bispecific antibody anti-GUCY2CxCD3.
    Title: Molecular insights into recognition of GUCY2C by T-cell engaging bispecific antibody anti-GUCY2CxCD3.
  2. Structural insight into guanylyl cyclase receptor hijacking of the kinase-Hsp90 regulatory mechanism.
    Title: Structural insight into guanylyl cyclase receptor hijacking of the kinase-Hsp90 regulatory mechanism.
  3. Intestinal neuropod cell GUCY2C regulates visceral pain.
    Title: Intestinal neuropod cell GUCY2C regulates visceral pain.
  4. Meconium Ileus due to GUCY2C gene mutations in three unrelated South Indian families.
    Title: Meconium Ileus due to GUCY2C gene mutations in three unrelated South Indian families.
  5. Intestinal Guanylate Cyclase-C mRNA Expression in Duodenum and Colon of Children.
    Title: Intestinal Guanylate Cyclase-C mRNA Expression in Duodenum and Colon of Children.
  6. Metabolic Syndrome Mediates ROS-miR-193b-NFYA-Dependent Downregulation of Soluble Guanylate Cyclase and Contributes to Exercise-Induced Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction.
    Title: Metabolic Syndrome Mediates ROS-miR-193b-NFYA-Dependent Downregulation of Soluble Guanylate Cyclase and Contributes to Exercise-Induced Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction.
  7. Novel GUCY2C variant causing familial diarrhea in a Mennonite kindred and a potential therapeutic approach.
    Title: Novel GUCY2C variant causing familial diarrhea in a Mennonite kindred and a potential therapeutic approach.
  8. Mutational landscape of receptor guanylyl cyclase C: Functional analysis and disease-related mutations.
    Title: Mutational landscape of receptor guanylyl cyclase C: Functional analysis and disease-related mutations.
  9. Silencing the intestinal GUCY2C tumor suppressor axis requires APC loss of heterozygosity.
    Title: Silencing the intestinal GUCY2C tumor suppressor axis requires APC loss of heterozygosity.
  10. Study reveals two discrete neuronal circuits expressing GUCY2C originating in the ventral premammillary nucleus in the hypothalamus and in the ventral tegmental area and substantia nigra in midbrain, which separately project to other sites throughout the brain.
    Title: Two distinct GUCY2C circuits with PMV (hypothalamic) and SN/VTA (midbrain) origin.
Submit: New GeneRIF Correction See all GeneRIFs (49)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Congenital diarrhea 6
MedGen: C3553270 OMIM: 614616 GeneReviews: Not available
not available
Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency
MedGen: C4518781 OMIM: 614665 GeneReviews: Not available
not available

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated 2013-09-18)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated 2013-09-18)

ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables GTP binding IEA
Inferred from Electronic Annotation
more info
  
enables guanylate cyclase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables guanylate cyclase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables peptide receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables toxic substance binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in cGMP biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in intracellular signal transduction IEA
Inferred from Electronic Annotation
more info
  
involved_in receptor guanylyl cyclase signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of cell population proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in response to toxic substance IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in endoplasmic reticulum membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
guanylyl cyclase C
Names
STA receptor
heat-stable enterotoxin receptor
intestinal guanylate cyclase
NP_004954.2
XP_011518933.1
XP_054227852.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_052021.1 RefSeqGene

    Range
    4987..88954
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_004963.4 → NP_004954.2  guanylyl cyclase C precursor

    See identical proteins and their annotated locations for NP_004954.2

    Status: REVIEWED

    Source sequence(s)
    AC007545, AC010168, AW848739, M73489, S57551
    Consensus CDS
    CCDS8664.1
    UniProtKB/Swiss-Prot
    B2RMY6, P25092
    Related
    ENSP00000261170.3, ENST00000261170.5
    Conserved Domains (5) summary
    cd06369
    Location:35 → 415
    PBP1_GC_C_enterotoxin_receptor; Ligand-binding domain of the membrane guanylyl cyclase C
    smart00044
    Location:788 → 979
    CYCc; Adenylyl- / guanylyl cyclase, catalytic domain
    cd14044
    Location:480 → 750
    PK_GC-C; Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C
    pfam00211
    Location:815 → 1002
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07714
    Location:502 → 745
    Pkinase_Tyr; Protein tyrosine kinase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    14612632..14696599 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011520631.3 → XP_011518933.1  guanylyl cyclase C isoform X1

    Conserved Domains (5) summary
    smart00044
    Location:706 → 897
    CYCc; Adenylyl- / guanylyl cyclase, catalytic domain
    cd14044
    Location:398 → 668
    PK_GC-C; Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C
    pfam00211
    Location:733 → 920
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07714
    Location:420 → 663
    Pkinase_Tyr; Protein tyrosine kinase
    cl10011
    Location:1 → 333
    Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    14490079..14574057 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054371877.1 → XP_054227852.1  guanylyl cyclase C isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P25092.2 GenPept UniProtKB/Swiss-Prot:P25092

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