CRH Gene

HGNC Family	Endogenous ligands
Name	corticotropin releasing hormone
Description	This gene encodes a member of the corticotropin-releasing factor family. The encoded preproprotein is proteolytically processed to generate the mature neuropeptide hormone. In response to stress, this hormone is secreted by the paraventricular nucleus (PVN) of the hypothalamus, binds to corticotropin releasing hormone receptors and stimulates the release of adrenocorticotropic hormone from the pituitary gland. Marked reduction in this protein has been observed in association with Alzheimer's disease. Autosomal recessive hypothalamic corticotropin deficiency has multiple and potentially fatal metabolic consequences including hypoglycemia and hepatitis. In addition to production in the hypothalamus, this protein is also synthesized in peripheral tissues, such as T lymphocytes, and is highly expressed in the placenta. In the placenta it is a marker that determines the length of gestation and the timing of parturition and delivery. A rapid increase in circulating levels of the hormone occurs at the onset of parturition, suggesting that, in addition to its metabolic functions, this protein may act as a trigger for parturition. [provided by RefSeq, Nov 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The corticotropin‐releasing hormone (CRH) system plays a pivotal role in integrating neuroendocrine, synaptic, and behavioral responses to stress. CRH is produced in key hypothalamic nuclei—most notably within the paraventricular nucleus—and serves as the principal trigger for activating the hypothalamic–pituitary–adrenal (HPA) axis, leading to adrenocorticotropic hormone (ACTH) release and subsequent glucocorticoid secretion (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition to its endocrine functions, CRH modulates central synaptic transmission: for instance, CRH receptor activation enhances N‐methyl‐D‐aspartate (NMDA) receptor–mediated currents in midbrain dopamine neurons and increases GABAergic neurotransmission in the central amygdala, thus influencing reward processing and the motivational aspects of substance use (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " Genetic and environmental influences also critically modulate CRH system function: polymorphisms in CRH receptor genes have been shown to alter HPA axis reactivity and confer differential vulnerability to depression, anxiety, and posttraumatic stress disorder (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": " Moreover, CRH expression is itself subject to regulation by peripheral signals and transcriptional modulators—such as adiponectin and MeCP2—that link energy homeostasis and neurodevelopmental status to stress responsiveness (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, recent work has demonstrated that CRH neurons are not only vital for the acute endocrine response to stress but also for orchestrating flexible, context‐dependent behavioral repertoires (for instance, in colonic motility and adaptive emotional responses), highlighting the region‐ and cell type–specific actions of CRH signaling (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yong Qi, Nobuhiko Takahashi, Stanley M Hileman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adiponectin acts in the brain to decrease body weight."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1029"}], "href": "https://doi.org/10.1038/nm1029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15077108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15077108"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "E B Binder, C B Nemeroff "}, {"type": "b", "children": [{"type": "t", "text": "The CRF system, stress, depression and anxiety-insights from human genetic studies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2009.141"}], "href": "https://doi.org/10.1038/mp.2009.141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20010888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20010888"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kirsty L Smith, Michael Patterson, Waljit S Dhillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuropeptide S stimulates the hypothalamo-pituitary-adrenal axis and inhibits food intake."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2005-1280"}], "href": "https://doi.org/10.1210/en.2005-1280"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16574794"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16574794"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mark A Ungless, Vineeta Singh, Tara L Crowder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Corticotropin-releasing factor requires CRF binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0896-6273(03)00461-6"}], "href": "https://doi.org/10.1016/s0896-6273(03"}, {"type": "t", "text": "00461-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12895416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12895416"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhiguo Nie, Paul Schweitzer, Amanda J Roberts, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1092550"}], "href": "https://doi.org/10.1126/science.1092550"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15001778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15001778"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Inge Sillaber, Gerhard Rammes, Stephan Zimmermann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhanced and delayed stress-induced alcohol drinking in mice lacking functional CRH1 receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1069836"}], "href": "https://doi.org/10.1126/science.1069836"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11988580"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11988580"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Rebekah G Bradley, Elisabeth B Binder, Michael P Epstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Influence of child abuse on adult depression: moderation by the corticotropin-releasing hormone receptor gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Gen Psychiatry (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/archgenpsychiatry.2007.26"}], "href": "https://doi.org/10.1001/archgenpsychiatry.2007.26"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18250257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18250257"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Christine Heim, Bekh Bradley, Tanja C Mletzko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of Childhood Trauma on Adult Depression and Neuroendocrine Function: Sex-Specific Moderation by CRH Receptor 1 Gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Behav Neurosci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/neuro.08.041.2009"}], "href": "https://doi.org/10.3389/neuro.08.041.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20161813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20161813"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Audrey R Tyrka, Lawrence H Price, Joel Gelernter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of childhood maltreatment with the corticotropin-releasing hormone receptor gene: effects on hypothalamic-pituitary-adrenal axis reactivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2009.05.012"}], "href": "https://doi.org/10.1016/j.biopsych.2009.05.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19596121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19596121"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Guilherme Polanczyk, Avshalom Caspi, Benjamin Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: replication and extension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Gen Psychiatry (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/archgenpsychiatry.2009.114"}], "href": "https://doi.org/10.1001/archgenpsychiatry.2009.114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19736354"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19736354"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sharyl L Fyffe, Jeff L Neul, Rodney C Samaco, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Hypothalamic CRH neurons orchestrate complex behaviours after stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms11937"}], "href": "https://doi.org/10.1038/ncomms11937"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27306314"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27306314"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Y Taché, V Martinez, L Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Pharmacol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjp.0705760"}], "href": "https://doi.org/10.1038/sj.bjp.0705760"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15100165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15100165"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Marloes J A G Henckens, Jan M Deussing, Alon Chen "}, {"type": "b", "children": [{"type": "t", "text": "Region-specific roles of the corticotropin-releasing factor-urocortin system in stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Neurosci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nrn.2016.94"}], "href": "https://doi.org/10.1038/nrn.2016.94"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27586075"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27586075"}]}]}]}
Synonyms	CRH1, CRF
Proteins	CRF_HUMAN
NCBI Gene ID	1392
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CRH has 8,211 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 113 datasets.

Click the + buttons to view associations for CRH from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CRH Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRH gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRH gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CRH gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CRH gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRH gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CRH gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CRH gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CRH gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CRH gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CRH gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CRH gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CRH gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CRH gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CRH gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CRH gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CRH gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CRH gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CRH protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CRH protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CRH protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CRH protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CRH gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CRH gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CRH gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CRH gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CRH gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CRH gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CRH gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CRH gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CRH gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CRH gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CRH protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CRH gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CRH gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CRH gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CRH from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CRH gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CRH gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CRH gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CRH gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.