DHPS Gene

Name	deoxyhypusine synthase
Description	This gene encodes a protein that is required for the formation of hypusine, a unique amino acid formed by the posttranslational modification of only one protein, eukaryotic translation initiation factor 5A. The encoded protein catalyzes the first step in hypusine formation by transferring the butylamine moiety of spermidine to a specific lysine residue of the eukaryotic translation initiation factor 5A precursor, forming an intermediate deoxyhypusine residue. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Deoxyhypusine synthase (DHPS) is a highly conserved enzyme that catalyzes the first and rate‐limiting step in the post‐translational formation of hypusine—a unique amino acid exclusively found on eukaryotic initiation factor 5A (eIF5A). By transferring the 4‑aminobutyl moiety from spermidine to a specific lysine residue on the eIF5A precursor, DHPS initiates a modification that is essential for eIF5A’s activity in facilitating translation elongation, resolving ribosomal stalling, and maintaining efficient protein synthesis under both homeostatic and stress conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Genetic studies in mice have underscored its fundamental role in development, as complete loss of DHPS results in early embryonic lethality while even partial reduction affects early cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its core function in translation, DHPS activity is increasingly linked to a spectrum of physiological and pathological processes. In cancer models, for instance, pharmacologic inhibition of DHPS using agents such as N1‐guanyl‑1,7‑diaminatoheptane (GC7) results in reduced eIF5A hypusination, which correlates with impaired tumor cell motility, invasion, and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, by modulating translational responses during cellular stress, DHPS plays a role in regulating stress granule dynamics and endoplasmic reticulum stress signaling; such mechanisms have implications in inflammatory responses and in the protection of β cells from cytokine‑ and ER‑stress–induced dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, DHPS is central not only to the hypusine activation of eIF5A and the regulation of translation elongation but also to broader biological processes including embryonic development, stress responses, and cancer progression. Its pivotal role in these pathways makes DHPS a promising target for therapeutic interventions aimed at blocking aberrant cell proliferation, tumor metastasis, and adverse immune or metabolic responses.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kazuhiro Nishimura, Seung Bum Lee, Jong Hwan Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Essential role of eIF5A-1 and deoxyhypusine synthase in mouse embryonic development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Amino Acids (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00726-011-0986-z"}], "href": "https://doi.org/10.1007/s00726-011-0986-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21850436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21850436"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Timothy C Umland, Edith C Wolff, Myung Hee Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A new crystal structure of deoxyhypusine synthase reveals the configuration of the active enzyme and of an enzyme.NAD.inhibitor ternary complex."}]}, {"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.M404095200"}], "href": "https://doi.org/10.1074/jbc.M404095200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15100216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15100216"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jong-Hwan Park, Edith C Wolff, J E Folk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reversal of the deoxyhypusine synthesis reaction. Generation of spermidine or homospermidine from deoxyhypusine by deoxyhypusine synthase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M304247200"}], "href": "https://doi.org/10.1074/jbc.M304247200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12788913"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12788913"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mythily Ganapathi, Leah R Padgett, Kentaro Yamada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recessive Rare Variants in Deoxyhypusine Synthase, an Enzyme Involved in the Synthesis of Hypusine, Are Associated with a Neurodevelopmental Disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2018.12.017"}], "href": "https://doi.org/10.1016/j.ajhg.2018.12.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30661771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30661771"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "T Muramatsu, K-I Kozaki, S Imoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The hypusine cascade promotes cancer progression and metastasis through the regulation of RhoA in squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2016.71"}], "href": "https://doi.org/10.1038/onc.2016.71"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27041563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27041563"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Esther M Levasseur, Kentaro Yamada, Annie R Piñeros, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.aax0715"}], "href": "https://doi.org/10.1126/scisignal.aax0715"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31796630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31796630"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Reiesha D Robbins, Sarah A Tersey, Takeshi Ogihara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of deoxyhypusine synthase enhances islet {beta} cell function and survival in the setting of endoplasmic reticulum stress and type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.170142"}], "href": "https://doi.org/10.1074/jbc.M110.170142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20956533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20956533"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Andrew T Templin, Bernhard Maier, Yurika Nishiki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deoxyhypusine synthase haploinsufficiency attenuates acute cytokine signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.10.7.15206"}], "href": "https://doi.org/10.4161/cc.10.7.15206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21389784"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21389784"}]}]}]}
Synonyms	DHS, MIG13, DS
Proteins	DHYS_HUMAN
NCBI Gene ID	1725
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DHPS has 6,224 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 119 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

DHPS 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 DHPS 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 DHPS 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 DHPS 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 DHPS 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 DHPS 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 DHPS 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 DHPS 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 DHPS 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 DHPS 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 DHPS 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 DHPS gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DHPS 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 DHPS gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DHPS protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DHPS 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 DHPS gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DHPS 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 DHPS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with DHPS gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of DHPS gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing DHPS 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 DHPS gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DHPS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DHPS 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 DHPS 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 DHPS 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 DHPS 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 DHPS gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DHPS gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DHPS gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DHPS gene/protein from the curated CTD Gene-Disease Associations dataset.
	DGIdb Drug Targets 2026	interacting drugs for DHPS protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DHPS 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 DHPS 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 DHPS 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 DHPS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DHPS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for DHPS protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at DHPS 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 DHPS gene from the ENCODE Transcription Factor Binding Site Profiles dataset.