HAX1 Gene

Name	HCLS1 associated protein X-1
Description	The protein encoded by this gene is known to associate with hematopoietic cell-specific Lyn substrate 1, a substrate of Src family tyrosine kinases. It also interacts with the product of the polycystic kidney disease 2 gene, mutations in which are associated with autosomal-dominant polycystic kidney disease, and with the F-actin-binding protein, cortactin. It was earlier thought that this gene product is mainly localized in the mitochondria, however, recent studies indicate it to be localized in the cell body. Mutations in this gene result in autosomal recessive severe congenital neutropenia, also known as Kostmann disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HAX1 is a multifunctional protein that plays a central role in maintaining cellular homeostasis by regulating apoptosis, cytoskeletal dynamics, and intracellular signaling. Predominantly localized to the mitochondria, HAX1 preserves the inner mitochondrial membrane potential and inhibits the activation of caspases (including caspase‐9), thereby protecting myeloid, lymphoid, neuronal, and cardiac cells from programmed cell death."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Its ability to interact with mitochondrial proteases, such as Parl and HtrA2, further underpins its anti‐apoptotic functions, and binding to other mitochondrial proteins like PHB2 helps integrate HAX1 into complexes that regulate organelle integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the hematopoietic system, mutations in HAX1 have been causally linked to severe congenital neutropenia and are associated with neurodevelopmental abnormalities, emphasizing its critical role in granulopoiesis and neural function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its mitochondrial actions, HAX1 also influences cell motility and cytoskeletal organization. Its binding to Gα13 and supervillin modulates actin dynamics, thereby affecting cellular migration and contributing to the metastatic potential of tumor cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, HAX1 is implicated in the regulation of inflammatory signaling; for instance, in fibroblasts, it associates with pre–interleukin‐1α and the IL-1 receptor type II to facilitate nuclear translocation of the cytokine precursor, thereby modulating downstream proinflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Regulation of HAX1 levels is also critical for cellular responses under stress. In triple-negative breast cancer stem cells, downregulation of miR-223 leads to elevated HAX1 levels, which in turn confer resistance to apoptotic stimuli such as TRAIL through the mitochondria/ROS pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In the heart, HAX1 modulates calcium homeostasis and contractility through its interaction with key Ca2+-handling proteins such as phospholamban and SERCA2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, emerging evidence indicates that aberrant HAX1 regulation can contribute to oncogenesis. In mantle cell lymphoma, for example, phosphorylations mediated by protein kinase Cδ direct nuclear FBXO25 to promote HAX1 degradation, suggesting that stabilization of HAX1 may act in a proto‐oncogenic manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies highlight HAX1 as a central regulator of apoptosis, cellular signaling, and cytoskeletal organization. Its multifaceted functions are essential for normal hematopoiesis, neuronal survival, and cardiac function, while dysregulation of HAX1—through genetic mutations or altered upstream control—has broad implications in immunodeficiency, cancer metastasis, and inflammatory pathologies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christoph Klein, Magda Grudzien, Giridharan Appaswamy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1940"}], "href": "https://doi.org/10.1038/ng1940"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17187068"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17187068"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jyh-Rong Chao, Evan Parganas, Kelli Boyd, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06604"}], "href": "https://doi.org/10.1038/nature06604"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18288109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18288109"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuchi Han, Yee-Shiuan Chen, Zhilin Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of HAX-1 protects cardiac myocytes from apoptosis through caspase-9 inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.RES.0000237387.05259.a5"}], "href": "https://doi.org/10.1161/01.RES.0000237387.05259.a5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16857965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16857965"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Katsumi Kasashima, Eriko Ohta, Yasuo Kagawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial functions and estrogen receptor-dependent nuclear translocation of pleiotropic human prohibitin 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M605260200"}], "href": "https://doi.org/10.1074/jbc.M605260200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17008324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17008324"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Manuela Germeshausen, Magda Grudzien, Cornelia Zeidler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-11-120667"}], "href": "https://doi.org/10.1182/blood-2007-11-120667"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18337561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18337561"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "G Carlsson, I van't Hooft, M Melin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific HAX1 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Intern Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2796.2008.01982.x"}], "href": "https://doi.org/10.1111/j.1365-2796.2008.01982.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18513342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18513342"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Tatsuya Morishima, Ken-ichiro Watanabe, Akira Niwa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic correction of HAX1 in induced pluripotent stem cells from a patient with severe congenital neutropenia improves defective granulopoiesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Haematologica (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3324/haematol.2013.083873"}], "href": "https://doi.org/10.3324/haematol.2013.083873"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23975175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23975175"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "V Radhika, Djamila Onesime, Ji Hee Ha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Galpha13 stimulates cell migration through cortactin-interacting protein Hax-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M408836200"}], "href": "https://doi.org/10.1074/jbc.M408836200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15339924"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15339924"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Tara C Smith, Zhiyou Fang, Elizabeth J Luna "}, {"type": "b", "children": [{"type": "t", "text": "Novel interactors and a role for supervillin in early cytokinesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cytoskeleton (Hoboken) (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cm.20449"}], "href": "https://doi.org/10.1002/cm.20449"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20309963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20309963"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yasushi Kawaguchi, Emi Nishimagi, Akiko Tochimoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intracellular IL-1alpha-binding proteins contribute to biological functions of endogenous IL-1alpha in systemic sclerosis fibroblasts."}]}, {"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.0603545103"}], "href": "https://doi.org/10.1073/pnas.0603545103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16971486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16971486"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xu Sun, Yongqing Li, Meizhu Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-223 Increases the Sensitivity of Triple-Negative Breast Cancer Stem Cells to TRAIL-Induced Apoptosis by Targeting HAX-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0162754"}], "href": "https://doi.org/10.1371/journal.pone.0162754"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27618431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27618431"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Wen Zhao, Jason R Waggoner, Zhi-Guo Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The anti-apoptotic protein HAX-1 is a regulator of cardiac function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0906998106"}], "href": "https://doi.org/10.1073/pnas.0906998106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19920172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19920172"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Ursula Baumann, Vanesa Fernández-Sáiz, Martina Rudelius, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of the PRKCD-FBXO25-HAX-1 axis attenuates the apoptotic response and drives lymphomagenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.3740"}], "href": "https://doi.org/10.1038/nm.3740"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25419709"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25419709"}]}]}]}
Synonyms	HCLSBP1, SCN3, HS1BP1
Proteins	HAX1_HUMAN
NCBI Gene ID	10456
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HAX1 has 8,874 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 124 datasets.

Click the + buttons to view associations for HAX1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HAX1 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 HAX1 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 HAX1 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 HAX1 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 HAX1 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 HAX1 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 HAX1 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 HAX1 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 HAX1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of HAX1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HAX1 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 HAX1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HAX1 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HAX1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HAX1 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 HAX1 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 HAX1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with HAX1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HAX1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HAX1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HAX1 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 HAX1 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 HAX1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HAX1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HAX1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HAX1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of HAX1 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 HAX1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving HAX1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving HAX1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with HAX1 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 HAX1 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 HAX1 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 HAX1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HAX1 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 HAX1 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 HAX1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HAX1 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 HAX1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with HAX1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with HAX1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.