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

Summary

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

Location:: 12p12.3

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (14612632..14696599, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (14490079..14574057, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (14765566..14849533, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
Intestinal neuropod cell GUCY2C regulates visceral pain.
Title: Intestinal neuropod cell GUCY2C regulates visceral pain.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-M73489 (e-PCR)
- UniSTS:34330

G41308 (e-PCR)
- UniSTS:4952

D12S1832 (e-PCR)
- UniSTS:20368

D12S1894 (e-PCR)
- UniSTS:32174

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 adenylate cyclase activity	IBA Inferred from Biological aspect of Ancestor 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

EC 4.6.1.2

XP_011518933.1

EC 4.6.1.2

XP_054227852.1

EC 4.6.1.2

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

NG_052021.1 RefSeqGene

Range

4987..88954

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

14612632..14696599 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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