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CRHR2 corticotropin releasing hormone receptor 2 [ Homo sapiens (human) ]

Gene ID: 1395, updated on 5-Mar-2024

Summary

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Official Symbol
CRHR2provided by HGNC
Official Full Name
corticotropin releasing hormone receptor 2provided by HGNC
Primary source
HGNC:HGNC:2358
See related
Ensembl:ENSG00000106113 MIM:602034; AllianceGenome:HGNC:2358
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
CRF2; CRFR2; CRF-RB; HM-CRF
Summary
The protein encoded by this gene belongs to the G-protein coupled receptor 2 family, and the subfamily of corticotropin releasing hormone receptor. This receptor shows high affinity for corticotropin releasing hormone (CRH), and also binds CRH-related peptides such as urocortin. CRH is synthesized in the hypothalamus, and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. Studies in mice suggest that this receptor maybe involved in mediating cardiovascular homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jan 2011]
Expression
Low expression observed in reference dataset See more
Orthologs
mouse all
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Genomic context

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See CRHR2 in Genome Data Viewer
Location:
7p14.3
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (30651942..30700103, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (30789546..30837766, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (30691558..30739719, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr7:30588305-30588806 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25815 Neighboring gene GARS1 divergent transcript Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:30633949-30634562 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:30634563-30635176 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:30635177-30635790 Neighboring gene glycyl-tRNA synthetase 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:30681423-30682118 Neighboring gene uncharacterized LOC124901609 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:30692507-30693496 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr7:30694345-30695544 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:30701754-30702296 Neighboring gene MPRA-validated peak6463 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18070 Neighboring gene uncharacterized LOC124901608 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:30727952-30728462 Neighboring gene uncharacterized LOC105375220 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:30747055-30747555 Neighboring gene uncharacterized LOC105375219 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:30766987-30767488 Neighboring gene INMT-MINDY4 readthrough (NMD candidate) Neighboring gene indolethylamine N-methyltransferase

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. Comorbidity of Novel CRHR2 Gene Variants in Type 2 Diabetes and Depression. Amin M, et al. Int J Mol Sci, 2022 Aug 29. PMID 36077219, Free PMC Article
  2. Association between genetic variant rs2267716 of CRHR2 gene with colorectal cancer. Ramírez-Guerrero AA, et al. J Investig Med, 2022 Apr. PMID 34969780
  3. Hypermethylation of Corticotropin Releasing Hormone Receptor-2 Gene in Ulcerative Colitis Associated Colorectal Cancer. Kobayashi M, et al. In Vivo, 2020 Jan-Feb. PMID 31882463, Free PMC Article
  4. Involvement of corticotropin-releasing factor and corticotropin-releasing factor 2 receptors in pathogenesis of ischemia/reperfusion-induced enteritis in rats. Takeuchi K, et al. J Physiol Pharmacol, 2016 Oct. PMID 28011950
  5. Corticotropin-Releasing Hormone Receptor 2 Gene Variants in Irritable Bowel Syndrome. Komuro H, et al. PLoS One, 2016. PMID 26808377, Free PMC Article

See all (116) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Novel corticotropin-releasing hormone receptor genes (CRHR1 and CRHR2) linkage to and association with polycystic ovary syndrome.
    Title: Novel corticotropin-releasing hormone receptor genes (CRHR1 and CRHR2) linkage to and association with polycystic ovary syndrome.
  2. Comorbidity of Novel CRHR2 Gene Variants in Type 2 Diabetes and Depression.
    Title: Comorbidity of Novel CRHR2 Gene Variants in Type 2 Diabetes and Depression.
  3. Defects in NLRP6, autophagy and goblet cell homeostasis are associated with reduced duodenal CRH receptor 2 expression in patients with functional dyspepsia.
    Title: Defects in NLRP6, autophagy and goblet cell homeostasis are associated with reduced duodenal CRH receptor 2 expression in patients with functional dyspepsia.
  4. Association between genetic variant rs2267716 of CRHR2 gene with colorectal cancer.
    Title: Association between genetic variant rs2267716 of CRHR2 gene with colorectal cancer.
  5. Different effects of chronic social defeat on social behavior and the brain CRF system in adult male C57 mice with different susceptibilities.
    Title: Different effects of chronic social defeat on social behavior and the brain CRF system in adult male C57 mice with different susceptibilities.
  6. Dysregulation of bladder corticotropin-releasing hormone receptor in the pathogenesis of human interstitial cystitis/bladder pain syndrome.
    Title: Dysregulation of bladder corticotropin-releasing hormone receptor in the pathogenesis of human interstitial cystitis/bladder pain syndrome.
  7. DNA methylation levels within CpG sites in NR3C1, CRH, CRHR1, and CRHR2 were associated with risk for major depressive disorder across adolescence and young adulthood.
    Title: DNA methylation of HPA-axis genes and the onset of major depressive disorder in adolescent girls: a prospective analysis.
  8. The activation of CRHR1 and CRHR2 remarkably reduced the conversion of microtubules-associated protein 1 light chain 3-B (LC3B) protein, LC3BI to LC3BII and hence repressed macroautophagy/autophagy, resulting in migration inhibition.
    Title: Activated CRH receptors inhibit autophagy by repressing conversion of LC3BI to LC3BII.
  9. Our results suggested that genetic variants of CRHR1 and CRHR2 genes in addition to physical negligence, and emotional and sexual abuse, contribute to increase risk of presented at least one suicide attempt
    Title: Effect of CRHR1 and CRHR2 gene polymorphisms and childhood trauma in suicide attempt.
  10. Detection of hypermethylation of CRHR2 may be promising for cancer screening in UC patients.
    Title: Hypermethylation of Corticotropin Releasing Hormone Receptor-2 Gene in Ulcerative Colitis Associated Colorectal Cancer.
Submit: New GeneRIF Correction See all GeneRIFs (73)

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

EBI GWAS Catalog

Description
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

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 G protein-coupled peptide receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables corticotrophin-releasing factor receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables corticotropin-releasing hormone receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables peptide hormone binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in adenylate cyclase-modulating G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cell surface receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to corticotropin-releasing hormone stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in long-term synaptic potentiation IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
is_active_in axon terminus IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in dendrite IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
corticotropin-releasing factor receptor 2
Names
CRH-R2

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_029169.1 RefSeqGene

    Range
    22648..53162
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001202475.1 → NP_001189404.1  corticotropin-releasing factor receptor 2 isoform 2 precursor

    See identical proteins and their annotated locations for NP_001189404.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains additional in-frame coding exons at the 5' end compared to variant 1, resulting in an isoform (2, also known as beta isoform) with a longer and distinct N-terminus compared to isoform 1. This receptor subtype was shown to mediate urocortin-induced MAPK activation in human myometrium (PMID:11117536).
    Source sequence(s)
    AC004976, AF011406, CN367944, DB308619, U34587
    Consensus CDS
    CCDS56478.1
    UniProtKB/Swiss-Prot
    Q13324
    Related
    ENSP00000340943.4, ENST00000348438.8
    Conserved Domains (2) summary
    smart00008
    Location:63 → 134
    HormR; Domain present in hormone receptors
    pfam00002
    Location:140 → 382
    7tm_2; 7 transmembrane receptor (Secretin family)

  2. NM_001202481.1 → NP_001189410.1  corticotropin-releasing factor receptor 2 isoform 3

    See identical proteins and their annotated locations for NP_001189410.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains additional exons at the 5' end compared to variant 1, resulting in a shorter isoform (3, also known as gamma isoform) with a distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC004976, AF011406, AF019381, CN367944, DB308619, U34587, Y10153
    Consensus CDS
    CCDS56477.1
    UniProtKB/Swiss-Prot
    Q13324
    Related
    ENSP00000344304.4, ENST00000341843.8
    Conserved Domains (2) summary
    smart00008
    Location:22 → 93
    HormR; Domain present in hormone receptors
    pfam00002
    Location:99 → 341
    7tm_2; 7 transmembrane receptor (Secretin family)

  3. NM_001202482.2 → NP_001189411.1  corticotropin-releasing factor receptor 2 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate in-frame acceptor splice site at one of the coding exons compared to variant 1, resulting in an isoform (4, also known as isoform desQ) 1 aa shorter than isoform 1.
    Source sequence(s)
    AC004976, AF011406, CN367944, DA808296, DB308619, EU012443, U34587
    UniProtKB/Swiss-Prot
    Q13324
    Conserved Domains (2) summary
    smart00008
    Location:36 → 107
    HormR; Domain present in hormone receptors
    pfam00002
    Location:112 → 354
    7tm_2; 7 transmembrane receptor (Secretin family)

  4. NM_001202483.2 → NP_001189412.1  corticotropin-releasing factor receptor 2 isoform 5

    See identical proteins and their annotated locations for NP_001189412.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) contains an additional exon at the penultimate position compared to variant 1, resulting in a frame-shift and a shorter isoform (5, also known as isoform D) with a distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC004976, AK313661, CN367944, DA808296, DB308619, EU012439, U34587
    Consensus CDS
    CCDS75576.1
    UniProtKB/Swiss-Prot
    Q13324
    Related
    ENSP00000426498.3, ENST00000506074.6
    Conserved Domains (2) summary
    smart00008
    Location:36 → 107
    HormR; Domain present in hormone receptors
    pfam00002
    Location:113 → 355
    7tm_2; 7 transmembrane receptor (Secretin family)

  5. NM_001883.5 → NP_001874.2  corticotropin-releasing factor receptor 2 isoform 1

    See identical proteins and their annotated locations for NP_001874.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript, and encodes isoform 1 (also known as alpha isoform).
    Source sequence(s)
    AC004976, AK313661, CN367944, DA808296, DB308619, U34587
    Consensus CDS
    CCDS5429.1
    UniProtKB/Swiss-Prot
    B2R967, B3SXS6, B3SXS7, B3SXS8, B3SXT0, F8WA81, O43461, Q13324, Q4QRJ4, Q99431
    UniProtKB/TrEMBL
    A0A090N7T4
    Related
    ENSP00000418722.1, ENST00000471646.6
    Conserved Domains (2) summary
    smart00008
    Location:36 → 107
    HormR; Domain present in hormone receptors
    cd15446
    Location:113 → 376
    7tmB1_CRF-R2; corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane G protein-coupled receptors

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

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    30651942..30700103 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047419893.1 → XP_047275849.1  corticotropin-releasing factor receptor 2 isoform X2

  2. XM_047419892.1 → XP_047275848.1  corticotropin-releasing factor receptor 2 isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    30789546..30837766 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054357267.1 → XP_054213242.1  corticotropin-releasing factor receptor 2 isoform X2

  2. XM_054357266.1 → XP_054213241.1  corticotropin-releasing factor receptor 2 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13324.2 GenPept UniProtKB/Swiss-Prot:Q13324

Gene LinkOut

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