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

    Gene ID: 2984, updated on 27-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
    mouse all
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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
    • 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
    		Compare labs
    Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency
    MedGen: C4518781 OMIM: 614665 GeneReviews: Not available
    		Compare labs

    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

    Gene LinkOut

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