DHDDS Gene

Name	dehydrodolichyl diphosphate synthase
Description	The protein encoded by this gene catalyzes cis-prenyl chain elongation to produce the polyprenyl backbone of dolichol, a glycosyl carrier lipid required for the biosynthesis of several classes of glycoproteins. Mutations in this gene are associated with retinitis pigmentosa type 59. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Dehydrodolichol diphosphate synthase (DHDDS) is a highly conserved enzyme that plays a pivotal role in dolichol biosynthesis—the production of a long‐chain polyisoprenoid essential for assembling dolichol‐linked oligosaccharides required for global N‐linked glycosylation. DHDDS catalyzes the successive condensation of isopentenyl diphosphate with farnesyl diphosphate, thereby supplying the dolichol needed for efficient protein glycosylation. In the retina, proper N‐glycosylation is critical for photoreceptor function; mutations in DHDDS—such as the recurrent Lys42Glu variant—compromise glycoprotein modification (including that of rhodopsin) and are causally linked to autosomal recessive retinitis pigmentosa, where altered dolichol chain length and reduced catalytic efficiency seem to destabilize photoreceptor disc membranes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Beyond retinal disease, DHDDS mutations—whether missense, splice‐site, or de novo variants—have been associated with broader multisystem disorders that include congenital disorders of glycosylation and neurodevelopmental syndromes marked by epilepsy, myoclonus, and ataxia, underscoring its vital role in neuronal as well as systemic metabolism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " Structural and functional investigations have revealed that DHDDS acts as the catalytic subunit within a heterotetrameric human cis‐prenyltransferase complex—assembled through interactions (notably with the Nogo‐B receptor, NgBR)—which is critical for dolichol production and thus for proper protein N‐glycosylation. Moreover, recent work has implicated altered expression of DHDDS in cancer biology; for example, circular RNA forms derived from the DHDDS locus have been shown to regulate oncogenic pathways in triple‐negative breast cancer by modulating microRNA activity and influencing tumor cell proliferation and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these studies highlight the centrality of DHDDS in lipid intermediate metabolism and protein glycosylation, with dysfunction contributing to a broad spectrum of human diseases ranging from inherited retinal dystrophies and neurodevelopmental disorders to oncogenic processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stephan Züchner, Julia Dallman, Rong Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.01.001"}], "href": "https://doi.org/10.1016/j.ajhg.2011.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21295283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21295283"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lina Zelinger, Eyal Banin, Alexey Obolensky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A missense mutation in DHDDS, encoding dehydrodolichyl diphosphate synthase, is associated with autosomal-recessive retinitis pigmentosa in Ashkenazi Jews."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.01.002"}], "href": "https://doi.org/10.1016/j.ajhg.2011.01.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21295282"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21295282"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rong Wen, Byron L Lam, Ziqiang Guan "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant dolichol chain lengths as biomarkers for retinitis pigmentosa caused by impaired dolichol biosynthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M043232"}], "href": "https://doi.org/10.1194/jlr.M043232"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24078709"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24078709"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "S Sabry, S Vuillaumier-Barrot, E Mintet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A case of fatal Type I congenital disorders of glycosylation (CDG I) associated with low dehydrodolichol diphosphate synthase (DHDDS) activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Orphanet J Rare Dis (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13023-016-0468-1"}], "href": "https://doi.org/10.1186/s13023-016-0468-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27343064"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27343064"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Byron L Lam, Stephan L Züchner, Julia Dallman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation K42E in dehydrodolichol diphosphate synthase (DHDDS) causes recessive retinitis pigmentosa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Exp Med Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-1-4614-3209-8_21"}], "href": "https://doi.org/10.1007/978-1-4614-3209-8_21"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24664694"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24664694"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Serena Galosi, Ban H Edani, Simone Martinelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "De novo DHDDS variants cause a neurodevelopmental and neurodegenerative disorder with myoclonus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awab299"}], "href": "https://doi.org/10.1093/brain/awab299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34382076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34382076"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Suping Cui, Yong Zhang, Li Xing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA dehydrodolichyl diphosphate synthase facilitated triple-negative breast cancer progression via miR-362-3p/DDX5 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Environ Toxicol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/tox.23500"}], "href": "https://doi.org/10.1002/tox.23500"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35343646"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35343646"}]}]}]}
Synonyms	DEDSM, HDS, RP59, CIT
Proteins	DHDDS_HUMAN
NCBI Gene ID	79947
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DHDDS has 8,437 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 125 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

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