HHEX Gene

HGNC Family	Homeoboxes
Name	hematopoietically expressed homeobox
Description	This gene encodes a member of the homeobox family of transcription factors, many of which are involved in developmental processes. Expression in specific hematopoietic lineages suggests that this protein may play a role in hematopoietic differentiation. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The homeobox transcription factor HHEX has emerged as a key regulator in multiple biological contexts. In genome‐wide association studies of type 2 diabetes, noncoding variants near or within HHEX (for example, rs1111875 and rs7923837) have been robustly linked to increased disease risk, an effect that is largely attributed to impaired pancreatic β‐cell function, including reduced insulin secretion and defective proinsulin processing."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " \n Moreover, detailed functional analyses have shown that conserved noncoding elements in linkage disequilibrium with the risk SNPs operate as tissue‐specific enhancers, driving HHEX expression in endoderm and pancreatic tissues. These findings suggest that HHEX contributes not only to the proper specification of pancreatic lineages but also to the regulation of insulin secretion in mature β‐cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in diabetes, HHEX also functions in other developmental contexts. In studies of hematopoietic progenitors, forced expression of HHEX was sufficient to induce self‐renewal of thymocytes, thereby implicating HHEX in the early stages of T cell leukemogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, experiments in vertebrate embryos have demonstrated that Wnt antagonists up‐regulate Hex in the underlying endoderm, an essential step for non–cell‐autonomous heart induction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, HHEX acts as a pleiotropic transcriptional regulator whose altered expression or genetic variation can compromise pancreatic β‐cell development and insulin secretion, thereby contributing to type 2 diabetes susceptibility, while its broader roles in endodermal lineage specification and in the regulation of progenitor cell self‐renewal underscore its importance in both metabolic and developmental pathways.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Richa Saxena, Benjamin F Voight, Valeriya Lyssenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1142358"}], "href": "https://doi.org/10.1126/science.1142358"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17463246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17463246"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Robert Sladek, Ghislain Rocheleau, Johan Rung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study identifies novel risk loci for type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature05616"}], "href": "https://doi.org/10.1038/nature05616"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17293876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17293876"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shintaro Omori, Yasushi Tanaka, Atsushi Takahashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db07-0979"}], "href": "https://doi.org/10.2337/db07-0979"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18162508"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18162508"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anja Ragvin, Enrico Moro, David Fredman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0911591107"}], "href": "https://doi.org/10.1073/pnas.0911591107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20080751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20080751"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Matthew P McCormack, Lauren F Young, Sumitha Vasudevan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1182378"}], "href": "https://doi.org/10.1126/science.1182378"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20093438"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20093438"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ann C Foley, Mark Mercola "}, {"type": "b", "children": [{"type": "t", "text": "Heart induction by Wnt antagonists depends on the homeodomain transcription factor Hex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1279405"}], "href": "https://doi.org/10.1101/gad.1279405"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15687261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15687261"}]}]}]}
Synonyms	PRH, PRHX, HMPH, HEX, HOX11L-PEN
Proteins	HHEX_HUMAN
NCBI Gene ID	3087
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HHEX has 8,602 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 120 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

HHEX Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by HHEX gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HHEX 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 HHEX 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 HHEX 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 HHEX 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 HHEX 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 HHEX 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 HHEX 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 HHEX 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 HHEX 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 HHEX 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 HHEX gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HHEX 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 HHEX gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HHEX 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 HHEX 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 HHEX gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HHEX protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HHEX protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HHEX 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 HHEX 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 HHEX gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HHEX gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HHEX gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HHEX gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of HHEX 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 HHEX gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with HHEX 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 HHEX 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 HHEX 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 HHEX 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 HHEX gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HHEX 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 HHEX 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 HHEX gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HHEX 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 HHEX from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with HHEX gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with HHEX 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 HHEX gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.