ADCYAP1 Gene

HGNC Family	Endogenous ligands
Name	adenylate cyclase activating polypeptide 1 (pituitary)
Description	This gene encodes a secreted proprotein that is further processed into multiple mature peptides. These peptides stimulate adenylate cyclase and increase cyclic adenosine monophosphate (cAMP) levels, resulting in the transcriptional activation of target genes. The products of this gene are key mediators of neuroendocrine stress responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ADCYAP1, which encodes the neuropeptide pituitary adenylate cyclase–activating polypeptide (PACAP), is a multifunctional signaling molecule whose diverse actions span central and peripheral systems. PACAP plays a prominent role in modulating stress responses by regulating both hormonal and neuronal circuits. For instance, genetic and biomarker studies have linked alterations in PACAP signaling to abnormal fear physiology and post‐traumatic stress disorder (PTSD), particularly in females, underscoring its involvement in stress‐related psychopathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, PACAP expressed by specific hypothalamic neurons provides excitatory inputs to hunger‐regulating AgRP neurons, which in turn trigger food intake under conditions of caloric deficit"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", while in the sympathoadrenal system PACAP functions as an “emergency response” cotransmitter that sustains epinephrine biosynthesis during metabolic stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In models of cerebral ischemia, PACAP has been shown to promote neuroprotection by stimulating interleukin‐6 production and activating downstream signaling cascades including STAT3 and ERK, thereby reducing neuronal apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, genetic variants in ADCYAP1 have been associated with abnormal neurodevelopment and cognitive deficits, as evidenced by reduced hippocampal volume and impaired memory performance in schizophrenia"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while structural studies of PACAP bound to its receptor have begun to elucidate the molecular determinants of high affinity and receptor selectivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Animal models further demonstrate that PACAP deficiency alters stress‐induced neuronal activation—in brain regions such as the hypothalamus, amygdala, and brainstem—and is accompanied by changes in anxiety‐ and depression‐like behaviors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Consistent with these findings, PACAP is necessary for the full activation of the hypothalamic–pituitary–adrenal (HPA) axis during chronic stress, as its absence results in attenuated corticosterone secretion and reduced transcription of corticotropin‐releasing hormone (CRH)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, the robust cytoprotective actions of PACAP across neural and peripheral tissues are highlighted by studies showing that the absence of endogenous PACAP renders tissues more vulnerable to a spectrum of insults, including ischemic, autoimmune, and excitotoxic challenges"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and that PACAP signaling can modulate intracellular pathways—via effectors such as Epac—to influence neuronal excitability independently of protein kinase A."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ADCYAP1/PACAP is a key neuropeptide integrator whose actions in stress adaptation, metabolic regulation, neuroprotection, and synaptic modulation make it a promising target for therapeutic interventions in neuropsychiatric, metabolic, and neurodegenerative disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kerry J Ressler, Kristina B Mercer, Bekh Bradley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09856"}], "href": "https://doi.org/10.1038/nature09856"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21350482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21350482"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michael J Krashes, Bhavik P Shah, Joseph C Madara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature12956"}], "href": "https://doi.org/10.1038/nature12956"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24487620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24487620"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Carol Hamelink, Olga Tjurmina, Ruslan Damadzic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.012608999"}], "href": "https://doi.org/10.1073/pnas.012608999"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11756684"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11756684"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hirokazu Ohtaki, Tomoya Nakamachi, Kenji Dohi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0600375103"}], "href": "https://doi.org/10.1073/pnas.0600375103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16651528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16651528"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "R Hashimoto, H Hashimoto, N Shintani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4001982"}], "href": "https://doi.org/10.1038/sj.mp.4001982"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17387318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17387318"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chaohong Sun, Danying Song, Rachel A Davis-Taber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Solution structure and mutational analysis of pituitary adenylate cyclase-activating polypeptide binding to the extracellular domain of PAC1-RS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0611397104"}], "href": "https://doi.org/10.1073/pnas.0611397104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17470806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17470806"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "B Gaszner, V Kormos, T Kozicz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The behavioral phenotype of pituitary adenylate-cyclase activating polypeptide-deficient mice in anxiety and depression tests is accompanied by blunted c-Fos expression in the bed nucleus of the stria terminalis, central projecting Edinger-Westphal nucleus, ventral lateral septum, and dorsal raphe nucleus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroscience (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuroscience.2011.11.046"}], "href": "https://doi.org/10.1016/j.neuroscience.2011.11.046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22178610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22178610"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Michael L Lehmann, Tomris Mustafa, Adrian M Eiden, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PACAP-deficient mice show attenuated corticosterone secretion and fail to develop depressive behavior during chronic social defeat stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Psychoneuroendocrinology (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.psyneuen.2012.09.006"}], "href": "https://doi.org/10.1016/j.psyneuen.2012.09.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23062748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23062748"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "D Reglodi, P Kiss, K Szabadfi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PACAP is an endogenous protective factor-insights from PACAP-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Neurosci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12031-012-9762-0"}], "href": "https://doi.org/10.1007/s12031-012-9762-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22528455"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22528455"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jeanne Ster, Frédéric De Bock, Nathalie C Guérineau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exchange protein activated by cAMP (Epac) mediates cAMP activation of p38 MAPK and modulation of Ca2+-dependent K+ channels in cerebellar neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0611031104"}], "href": "https://doi.org/10.1073/pnas.0611031104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17284589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17284589"}]}]}]}
Synonyms	PACAP
Proteins	PACA_HUMAN
NCBI Gene ID	116
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ADCYAP1 has 7,053 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 108 datasets.

Click the + buttons to view associations for ADCYAP1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ADCYAP1 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 ADCYAP1 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 ADCYAP1 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 ADCYAP1 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 ADCYAP1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ADCYAP1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ADCYAP1 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 ADCYAP1 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 ADCYAP1 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 ADCYAP1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of ADCYAP1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ADCYAP1 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 ADCYAP1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ADCYAP1 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 ADCYAP1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ADCYAP1 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 ADCYAP1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ADCYAP1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ADCYAP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ADCYAP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ADCYAP1 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 ADCYAP1 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 ADCYAP1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ADCYAP1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ADCYAP1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ADCYAP1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ADCYAP1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ADCYAP1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ADCYAP1 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 ADCYAP1 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 ADCYAP1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ADCYAP1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ADCYAP1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ADCYAP1 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 ADCYAP1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ADCYAP1 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 ADCYAP1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ADCYAP1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ADCYAP1 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 ADCYAP1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ADCYAP1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.