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GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CRH
corticotropin releasing hormone
Chromosome 8 · 8q13.1
NCBI Gene: 1392Ensembl: ENSG00000147571.6HGNC: HGNC:2355UniProt: A0A0S2Z478
229PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
synaptic transmission, dopaminergicpositive regulation of corticotropin secretionprotein bindingfemale pregnancyautosomal dominant nocturnal frontal lobe epilepsysleep-related hypermotor epilepsyfamilial sleep-related hypermotor epilepsymalnutrition
✦AI Summary

CRH (corticotropin-releasing hormone) is a neuropeptide hormone that serves as the primary regulator of the hypothalamic-pituitary-adrenal (HPA) axis stress response system 1. As the main coordinator of adaptive responses to stressors, CRH stimulates corticotropin secretion from the anterior pituitary, ultimately triggering glucocorticoid release 1. Beyond its endocrine function, CRH acts as a neuromodulator, activating CRH receptors on hippocampal neurons to influence synaptic efficacy and cognition; however, pathological CRH levels contribute to neuronal death 2. CRH modulates multiple physiological systems: it inhibits appetite and reproductive function while activating thermogenesis and the dopaminergic reward system 1. CRH also exerts bidirectional sleep regulation through reciprocal interactions with growth hormone-releasing hormone 3. Locally, endometrial and placental CRH regulate embryo implantation and maternal immune tolerance through Fas ligand modulation 4. CRH receptors are involved in female reproductive axis regulation and trigger parturition 5. Dysregulated CRH signaling associates with vitiligo susceptibility through CRH-R1 polymorphisms 6 and contributes to obstetrical complications including preeclampsia and preterm delivery 5. CRH antagonists show therapeutic potential for melancholic depression and anxiety 1.

Sources cited
1
CRH coordinates stress system response, stimulates corticotropin secretion, modulates appetite/thermogenesis/reproductive function, and potential therapeutic targets in depression and anxiety
PMID: 12377295
2
CRH activates receptors on hippocampal neurons affecting synaptic efficacy and cognition; pathological levels contribute to neuronal death
PMID: 12220880
3
CRH has sleep-impairing role through reciprocal interaction with sleep-promoting GHRH
PMID: 12700062
4
Endometrial and placental CRH regulate embryo implantation and maternal immune tolerance via Fas ligand modulation
PMID: 15288181
5
CRH receptors regulate hypothalamic-pituitary-ovarian axis and parturition; abnormal signaling contributes to preeclampsia and preterm delivery
PMID: 28240193
6
CRH-R1 polymorphisms associate with vitiligo susceptibility
PMID: 35905107
Disease Associationsⓘ20
autosomal dominant nocturnal frontal lobe epilepsyOpen Targets
0.37Weak
sleep-related hypermotor epilepsyOpen Targets
0.37Weak
familial sleep-related hypermotor epilepsyOpen Targets
0.37Weak
malnutritionOpen Targets
0.22Weak
alcohol drinkingOpen Targets
0.20Weak
type 2 diabetes mellitusOpen Targets
0.18Weak
obesityOpen Targets
0.16Weak
Abnormality of the skeletal systemOpen Targets
0.15Weak
AnxietyOpen Targets
0.11Weak
metabolic syndromeOpen Targets
0.11Weak
irritable bowel syndromeOpen Targets
0.10Weak
post-traumatic stress disorderOpen Targets
0.10Weak
diabetes mellitusOpen Targets
0.10Suggestive
major depressive disorderOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
schizophreniaOpen Targets
0.09Suggestive
melanomaOpen Targets
0.09Suggestive
colitisOpen Targets
0.09Suggestive
Pallister-Hall syndromeOpen Targets
0.09Suggestive
Lewy body dementiaOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
OXTRProtein interaction100%CRHR2Protein interaction100%UCN3Protein interaction100%UCN2Protein interaction100%VIPProtein interaction99%GCGProtein interaction98%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
10%
Ovary
0%
Heart
0%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
CRHOXTRCRHR2UCN3UCN2VIPGCG
PROTEIN STRUCTURE
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PDB3EHU · 1.96 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.72LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.93 [0.51–1.72]
RankingsWhere CRH stands among ~20K protein-coding genes
  • #1,759of 20,598
    Most Researched229 · top 10%
  • #16,188of 17,882
    Most Constrained (LOEUF)1.72
Genes detectedCRH
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress.
PMID: 12377295
J Psychosom Res · 2002
1.00
2
Gene polymorphisms and serum levels of BDNF and CRH in vitiligo patients.
PMID: 35905107
PLoS One · 2022
0.90
3
Stressed-out, or in (utero)?
PMID: 12220880
Trends Neurosci · 2002
0.80
4
Neurotensin and CRH interactions augment human mast cell activation.
PMID: 23155429
PLoS One · 2012
0.76
5
Pharmacology of ovine and human CRH.
PMID: 2832286
Horm Metab Res Suppl · 1987
0.72