BACE1 Gene

Name	beta-site APP-cleaving enzyme 1
Description	This gene encodes a member of the peptidase A1 family of aspartic proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protease. This transmembrane protease catalyzes the first step in the formation of amyloid beta peptide from amyloid precursor protein. Amyloid beta peptides are the main constituent of amyloid beta plaques, which accumulate in the brains of human Alzheimer's disease patients. [provided by RefSeq, Nov 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BACE1 is a transmembrane aspartyl protease that functions as the β‐secretase responsible for the initial cleavage of the amyloid precursor protein (APP), thereby initiating the amyloidogenic cascade that leads to the generation of neurotoxic amyloid‑β (Aβ) peptides implicated in Alzheimer’s disease (AD) pathogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In AD brains, BACE1 levels and activity are frequently elevated in regions undergoing amyloid deposition, suggesting that an increase in BACE1 expression may drive a pathogenic feed‑forward loop that exacerbates Aβ production."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " Moreover, regulatory mechanisms—such as stabilization by its natural antisense transcript (BACE1‑AS), modulation by inflammatory (e.g. NF‑κB) and oxidative stress signals, and control by kinases like GSK3β—further influence BACE1 gene transcription and protein stability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": " In addition to its canonical role in Aβ production, BACE1 performs important physiological functions; for instance, it cleaves type‑III neuregulin‑1 (NRG1) which is crucial for the proper myelination of peripheral nerves and for regulating myelin sheath thickness in both the central and peripheral nervous systems."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Pharmacological or gene‑based inhibition of BACE1 lowers cerebral Aβ levels and has been shown to rescue memory deficits in AD models"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "; however, these data also caution that targeting BACE1 must carefully account for its non‑amyloidogenic roles in neuronal development and myelination, as complete loss or excessive inhibition may lead to deleterious side effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lydia Alvarez-Erviti, Yiqi Seow, Haifang Yin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Biotechnol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nbt.1807"}], "href": "https://doi.org/10.1038/nbt.1807"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21423189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21423189"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Joanna L Jankowsky, Daniel J Fadale, Jeffrey Anderson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddh019"}], "href": "https://doi.org/10.1093/hmg/ddh019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14645205"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14645205"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Christopher J Phiel, Christina A Wilson, Virginia M-Y Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01640"}], "href": "https://doi.org/10.1038/nature01640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12761548"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12761548"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hiroaki Fukumoto, Bonnie S Cheung, Bradley T Hyman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Neurol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/archneur.59.9.1381"}], "href": "https://doi.org/10.1001/archneur.59.9.1381"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12223024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12223024"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jie Zhao, Yifan Fu, Marina Yasvoina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Beta-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: implications for Alzheimer's disease pathogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4396-06.2007"}], "href": "https://doi.org/10.1523/JNEUROSCI.4396-06.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17409228"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17409228"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chia-Hsiung Chen, Weihui Zhou, Shengchun Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased NF-κB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Neuropsychopharmacol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S1461145711000149"}], "href": "https://doi.org/10.1017/S1461145711000149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21329555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21329555"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mohammad Ali Faghihi, Farzaneh Modarresi, Ahmad M Khalil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1784"}], "href": "https://doi.org/10.1038/nm1784"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18587408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18587408"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Elena Tamagno, Paola Bardini, Alessandra Obbili, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oxidative stress increases expression and activity of BACE in NT2 neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/nbdi.2002.0515"}], "href": "https://doi.org/10.1006/nbdi.2002.0515"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12270690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12270690"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Philip T T Ly, Yili Wu, Haiyan Zou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of GSK3β-mediated BACE1 expression reduces Alzheimer-associated phenotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI64516"}], "href": "https://doi.org/10.1172/JCI64516"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23202730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23202730"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Michael Willem, Alistair N Garratt, Bozidar Novak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Control of peripheral nerve myelination by the beta-secretase BACE1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1132341"}], "href": "https://doi.org/10.1126/science.1132341"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16990514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16990514"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xiangyou Hu, Caitlin W Hicks, Wanxia He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bace1 modulates myelination in the central and peripheral nervous system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn1797"}], "href": "https://doi.org/10.1038/nn1797"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17099708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17099708"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Masuo Ohno, Evgeny A Sametsky, Linda H Younkin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0896-6273(03)00810-9"}], "href": "https://doi.org/10.1016/s0896-6273(03"}, {"type": "t", "text": "00810-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14715132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14715132"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Riqiang Yan, Robert Vassar "}, {"type": "b", "children": [{"type": "t", "text": "Targeting the β secretase BACE1 for Alzheimer's disease therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lancet Neurol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S1474-4422(13)70276-X"}], "href": "https://doi.org/10.1016/S1474-4422(13"}, {"type": "t", "text": "70276-X) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24556009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24556009"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Diana Dominguez, Jos Tournoy, Dieter Hartmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M505249200"}], "href": "https://doi.org/10.1074/jbc.M505249200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15987683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15987683"}]}]}]}
Synonyms	BACE, ASP2, HSPC104
Proteins	BACE1_HUMAN
NCBI Gene ID	23621
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

BACE1 has 9,581 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 131 datasets.

Click the + buttons to view associations for BACE1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

BACE1 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 BACE1 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 BACE1 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 BACE1 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 BACE1 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 BACE1 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 BACE1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving BACE1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of BACE1 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 BACE1 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 BACE1 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 BACE1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of BACE1 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 BACE1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with BACE1 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 BACE1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of BACE1 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 BACE1 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 BACE1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing BACE1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing BACE1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing BACE1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with BACE1 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 BACE1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing BACE1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of BACE1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with BACE1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with BACE1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with BACE1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with BACE1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by BACE1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with BACE1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with BACE1 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 BACE1 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 BACE1 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 BACE1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with BACE1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for BACE1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at BACE1 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 BACE1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of BACE1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.