AHSA1 Gene

Name	AHA1, activator of heat shock 90kDa protein ATPase homolog 1 (yeast)
Description	Enables ATPase activator activity; Hsp90 protein binding activity; and protein-folding chaperone binding activity. Involved in positive regulation of ATP-dependent activity. Located in cytosol. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Activator of Hsp90 ATPase 1 (Aha1, also known as AHSA1) is a pivotal cochaperone that directly binds to Hsp90 in order to stimulate its intrinsic, yet low, ATPase activity. Structural and biochemical studies indicate that Aha1 employs both its N‐ and C‐terminal domains to bridge the dimer interface of Hsp90, thereby modulating conformational rearrangements that control the “dwell time” of client proteins during their folding cycle."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functionally, Aha1 exerts a broad influence on proteostasis by accelerating the Hsp90 ATPase cycle in a manner that impacts the maturation and trafficking of diverse client proteins. For example, modulation of Aha1 levels has been shown to affect the folding efficiency of the cystic fibrosis transmembrane conductance regulator (CFTR) – where partial silencing of Aha1 improves the folding and trafficking of the misfolded ΔF508 mutant – as well as the accumulation and aggregation of the intrinsically disordered tau protein, which is implicated in neurodegenerative disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, phosphorylation‐dependent modulation of Hsp90 has been shown to promote recruitment of Aha1, integrating upstream signal transduction events with the chaperone’s conformational dynamics. This regulatory mechanism not only fine‐tunes the activation of kinase and non‐kinase clients but also influences other cellular processes such as alternative splicing, underscoring the broad impact of Aha1 on cell signaling and protein quality control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings position Aha1 as a central regulator of the Hsp90 chaperone machinery. Its ability to modulate ATPase activity and client protein folding renders it a potential therapeutic target for correcting misfolding disorders and mitigating toxic protein aggregation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiaodong Wang, John Venable, Paul LaPointe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2006.09.043"}], "href": "https://doi.org/10.1016/j.cell.2006.09.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17110338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17110338"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Barry Panaretou, Giuliano Siligardi, Philippe Meyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1097-2765(02)00785-2"}], "href": "https://doi.org/10.1016/s1097-2765(02"}, {"type": "t", "text": "00785-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12504007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12504007"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Atanas V Koulov, Paul LaPointe, Bingwen Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biological and structural basis for Aha1 regulation of Hsp90 ATPase activity in maintaining proteostasis in the human disease cystic fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e09-12-1017"}], "href": "https://doi.org/10.1091/mbc.e09-12-1017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20089831"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20089831"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Guido Veit, Kathryn Oliver, Pirjo M Apaja, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribosomal Stalk Protein Silencing Partially Corrects the ΔF508-CFTR Functional Expression Defect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pbio.1002462"}], "href": "https://doi.org/10.1371/journal.pbio.1002462"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27168400"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27168400"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lindsey B Shelton, Jeremy D Baker, Dali Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hsp90 activator Aha1 drives production of pathological tau aggregates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1707039114"}], "href": "https://doi.org/10.1073/pnas.1707039114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28827321"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28827321"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wanping Xu, Mehdi Mollapour, Chrisostomos Prodromou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynamic tyrosine phosphorylation modulates cycling of the HSP90-P50(CDC37)-AHA1 chaperone machine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2012.05.015"}], "href": "https://doi.org/10.1016/j.molcel.2012.05.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22727666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22727666"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wanping Xu, Kristin Beebe, Juan D Chavez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hsp90 middle domain phosphorylation initiates a complex conformational program to recruit the ATPase-stimulating cochaperone Aha1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-10463-y"}], "href": "https://doi.org/10.1038/s41467-019-10463-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31189925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31189925"}]}]}]}
Synonyms	hAha1, AHA1, C14ORF3
Proteins	AHSA1_HUMAN
NCBI Gene ID	10598
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AHSA1 has 8,004 functional associations with biological entities spanning 8 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) extracted from 111 datasets.

Click the + buttons to view associations for AHSA1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

AHSA1 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 AHSA1 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 AHSA1 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 AHSA1 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 AHSA1 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 AHSA1 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 AHSA1 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 AHSA1 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 AHSA1 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 AHSA1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of AHSA1 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 AHSA1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AHSA1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AHSA1 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 AHSA1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AHSA1 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 AHSA1 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 AHSA1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing AHSA1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing AHSA1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing AHSA1 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 AHSA1 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 AHSA1 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 AHSA1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AHSA1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AHSA1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AHSA1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of AHSA1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by AHSA1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with AHSA1 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 AHSA1 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 AHSA1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with AHSA1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at AHSA1 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 AHSA1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of AHSA1 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 AHSA1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of AHSA1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with AHSA1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing AHSA1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of AHSA1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.