HEXA Gene

Name	hexosaminidase A (alpha polypeptide)
Description	This gene encodes a member of the glycosyl hydrolase 20 family of proteins. The encoded preproprotein is proteolytically processed to generate the alpha subunit of the lysosomal enzyme beta-hexosaminidase. This enzyme, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene lead to an accumulation of GM2 ganglioside in neurons, the underlying cause of neurodegenerative disorders termed the GM2 gangliosidoses, including Tay-Sachs disease (GM2-gangliosidosis type I). Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The α‐subunit of β‐hexosaminidase A (HEXA) is a lysosomal enzyme that plays a critical role in the degradation of GM2 ganglioside, a major glycosphingolipid in neuronal membranes. In healthy cells, HEXA coordinates with its β‐subunit partner to catalyze the conversion of GM2 to GM3, thereby preventing the toxic accumulation of GM2 within lysosomes. Disruption of HEXA function – whether through mutations that impair proper folding, subunit assembly, trafficking, or by affecting its stability – results in reduced enzymatic activity and subsequent lysosomal storage of GM2, a hallmark of Tay–Sachs disease (1,2,3,4). Several mechanistic studies indicate that misfolded HEXA protein is cleared via endoplasmic reticulum‐associated degradation, and that its activity can be partially restored by modulating the cellular folding environment with temperature shifts or chemical chaperones (2,5). Furthermore, recent work has demonstrated that specific chaperones, including progranulin and engineered derivatives thereof, can bind directly to HEXA, enhancing its lysosomal delivery and activity, and effectively reducing GM2 storage (1,4). In addition, investigations into pseudodeficiency alleles suggest that certain sequence variants may lead to markedly decreased in vitro enzymatic activity while still retaining adequate in vivo function, underscoring the importance of accurate biochemical and genetic assessments in diagnosis (7). Collectively, these studies highlight HEXA’s indispensable role in lysosomal catabolism of gangliosides and illustrate how perturbations in its function give rise to neurodegenerative pathology."}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yuehong Chen, Jinlong Jian, Aubryanna Hettinghouse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Progranulin associates with hexosaminidase A and ameliorates GM2 ganglioside accumulation and lysosomal storage in Tay-Sachs disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Med (Berl) (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00109-018-1703-0"}], "href": "https://doi.org/10.1007/s00109-018-1703-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30341570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30341570"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Devin Dersh, Yuichiro Iwamoto, Yair Argon "}, {"type": "b", "children": [{"type": "t", "text": "Tay-Sachs disease mutations in HEXA target the α chain of hexosaminidase A to endoplasmic reticulum-associated degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E16-01-0012"}], "href": "https://doi.org/10.1091/mbc.E16-01-0012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27682588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27682588"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Volkan Seyrantepe, Pablo Lema, Aurore Caqueret, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mice doubly-deficient in lysosomal hexosaminidase A and neuraminidase 4 show epileptic crises and rapid neuronal loss."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1001118"}], "href": "https://doi.org/10.1371/journal.pgen.1001118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20862357"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20862357"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Valeriya V Solovyeva, Alisa A Shaimardanova, Daria S Chulpanova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "New Approaches to Tay-Sachs Disease Therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Physiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fphys.2018.01663"}], "href": "https://doi.org/10.3389/fphys.2018.01663"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30524313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30524313"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kozo Matsushita, Tadahiro Numakawa, Haruki Odaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Presynaptic Dysfunction in Neurons Derived from Tay-Sachs iPSCs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroscience (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuroscience.2019.06.026"}], "href": "https://doi.org/10.1016/j.neuroscience.2019.06.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31283907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31283907"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Valeria Bertani, Simona Prioni, Rosanna Di Lecce, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A pathogenic HEXA missense variant in wild boars with Tay-Sachs disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2021.05.001"}], "href": "https://doi.org/10.1016/j.ymgme.2021.05.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34119419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34119419"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "N V Olkhovych, N G Gorovenko "}, {"type": "b", "children": [{"type": "t", "text": "Determination of frequencies of alleles, associated with the pseudodeficiency of lysosomal hydrolases, in population of Ukraine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ukr Biochem J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15407/ubj88.05.096"}], "href": "https://doi.org/10.15407/ubj88.05.096"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29235819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29235819"}]}]}]}
Synonyms	TSD
Proteins	HEXA_HUMAN
NCBI Gene ID	3073
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HEXA has 7,613 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 128 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

HEXA 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 HEXA 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 HEXA 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 HEXA 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 HEXA 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 HEXA 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 HEXA 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 HEXA 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 HEXA 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 HEXA 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 HEXA 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 HEXA gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HEXA protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HEXA 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 HEXA gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HEXA 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 HEXA 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 HEXA gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with HEXA gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing HEXA protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of HEXA gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HEXA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HEXA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HEXA 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 HEXA 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 HEXA gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HEXA gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HEXA gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HEXA gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of HEXA 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 HEXA gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving HEXA gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving HEXA gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HEXA 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 HEXA 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 HEXA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HEXA 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 HEXA 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 HEXA gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HEXA 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 HEXA from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.