HOXD3 Gene

HGNC Family	Homeoboxes
Name	homeobox D3
Description	This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located at 2q31-2q37 chromosome regions. Deletions that removed the entire HOXD gene cluster or 5' end of this cluster have been associated with severe limb and genital abnormalities. The protein encoded by this gene may play a role in the regulation of cell adhesion processes. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HOXD3 is a homeobox transcription factor that plays multifaceted roles in promoting both endothelial and tumor cell behaviors. In endothelial cells, HOXD3 directly binds to the promoters of key integrin subunits (including α5β1 and αvβ3) and—in cooperation with cofactors such as PBX1—enhances cell migration and neovessel formation, thereby driving angiogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the context of tissue repair, gene transfer of HOXD3 into diabetic wounds increases angiogenesis and collagen deposition, ultimately accelerating wound closure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In several cancer settings, HOXD3 appears to function as a transcriptional activator that facilitates oncogenic processes. For instance, in colorectal carcinoma, downregulation of HOXD3 by the long noncoding RNA HOXD‑AS1 leads to repression of integrin β3 transcription and subsequent attenuation of MAPK/AKT signaling, highlighting its oncogenic potential when derepressed."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In lung squamous cell carcinoma, increased expression of HOXD3 is part of a broader upregulation of HOXD family members that serve as potential diagnostic markers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, in hepatocellular carcinoma, HOXD3 is directly targeted by the tumor‐suppressive microRNA miR‑203a; suppression of HOXD3 attenuates activation of the EGFR/AKT and ERK pathways, leading to cell cycle arrest and enhanced apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Finally, in prostate cancer, hypermethylation of the HOXD3 promoter is correlated with higher tumor grade and a reduced recurrence‐free survival, underscoring its potential prognostic value."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these studies indicate that HOXD3 functions as a pivotal regulator of angiogenesis, cell migration, and tumor progression by modulating integrin expression and key signaling pathways, and that its expression is tightly controlled by epigenetic and posttranscriptional mechanisms.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nancy J Boudreau, Judith A Varner "}, {"type": "b", "children": [{"type": "t", "text": "The homeobox transcription factor Hox D3 promotes integrin alpha5beta1 expression and function during angiogenesis."}]}, {"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.M305190200"}], "href": "https://doi.org/10.1074/jbc.M305190200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14610084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14610084"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "A Charboneau, L East, N Mulholland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pbx1 is required for Hox D3-mediated angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Angiogenesis (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10456-005-9016-7"}], "href": "https://doi.org/10.1007/s10456-005-9016-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16328158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16328158"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yongmei Chen, Bin Xu, Gemma Arderiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retroviral delivery of homeobox D3 gene induces cerebral angiogenesis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cereb Blood Flow Metab (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/01.WCB.0000141770.09022.AB"}], "href": "https://doi.org/10.1097/01.WCB.0000141770.09022.AB"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15545924"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15545924"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Min-Hui Yang, Li Zhao, Lan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear lncRNA HOXD-AS1 suppresses colorectal carcinoma growth and metastasis via inhibiting HOXD3-induced integrin β3 transcriptional activating and MAPK/AKT signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12943-019-0955-9"}], "href": "https://doi.org/10.1186/s12943-019-0955-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30823921"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30823921"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lianmin Bao, Yong Zhang, Jian Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variations of chromosome 2 gene expressions among patients with lung cancer or non-cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Toxicol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10565-016-9343-z"}], "href": "https://doi.org/10.1007/s10565-016-9343-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27301951"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27301951"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lumin Wang, Hongfei Sun, Xiaofei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EGR1 mediates miR-203a suppress the hepatocellular carcinoma cells progression by targeting HOXD3 through EGFR signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.9605"}], "href": "https://doi.org/10.18632/oncotarget.9605"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27244890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27244890"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lumin Wang, Dongdong Tong, Qingqing Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HOXD3 targeted by miR-203a suppresses cell metastasis and angiogenesis through VEGFR in human hepatocellular carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-20859-3"}], "href": "https://doi.org/10.1038/s41598-018-20859-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29402992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29402992"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ken J Kron, Liyang Liu, Vaijayanti V Pethe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA methylation of HOXD3 as a marker of prostate cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lab Invest (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/labinvest.2010.57"}], "href": "https://doi.org/10.1038/labinvest.2010.57"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20212450"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20212450"}]}]}]}
Synonyms	HOX4A, HOX-4.1
Proteins	HXD3_HUMAN
NCBI Gene ID	3232
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HOXD3 has 4,296 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 108 datasets.

Click the + buttons to view associations for HOXD3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HOXD3 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 HOXD3 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 HOXD3 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 HOXD3 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 HOXD3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HOXD3 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 HOXD3 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 HOXD3 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 HOXD3 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 HOXD3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HOXD3 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 HOXD3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HOXD3 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 HOXD3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HOXD3 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 HOXD3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of HOXD3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of HOXD3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HOXD3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HOXD3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HOXD3 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 HOXD3 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 HOXD3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HOXD3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HOXD3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HOXD3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by HOXD3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with HOXD3 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 HOXD3 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 HOXD3 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 HOXD3 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 HOXD3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HOXD3 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 HOXD3 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 HOXD3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HOXD3 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 HOXD3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with HOXD3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with HOXD3 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 HOXD3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with HOXD3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.