DHTKD1 Gene

Name	dehydrogenase E1 and transketolase domain containing 1
Description	This gene encodes a component of a mitochondrial 2-oxoglutarate-dehydrogenase-complex-like protein involved in the degradation pathways of several amino acids, including lysine. Mutations in this gene are associated with 2-aminoadipic 2-oxoadipic aciduria and Charcot-Marie-Tooth Disease Type 2Q. [provided by RefSeq, May 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DHTKD1 encodes the E1 subunit of the mitochondrial 2‐oxoadipate dehydrogenase complex, a key enzyme in the oxidative decarboxylation of 2‐oxoadipate—a pivotal step in lysine and tryptophan catabolism. In doing so, DHTKD1 regulates the levels of metabolic intermediates such as 2‐aminoadipate, with alterations shown to influence glucose homeostasis and diabetes risk."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mutations in DHTKD1 can disrupt its enzymatic activity—impairing the conversion of 2-oxoadipate to glutaryl‐CoA—and cause metabolic disorders such as 2‐aminoadipic/2‐oxoadipic aciduria. Notably, defective DHTKD1 has also been linked to neurological conditions including Charcot–Marie–Tooth disease type 2Q. In these cases the mutations not only hinder lysine degradation but also compromise mitochondrial energy production and biogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural analyses have further revealed that DHTKD1 is specifically tuned to accommodate a longer dicarboxylic substrate compared with its paralog 2‐oxoglutarate dehydrogenase, and that disease‐associated missense mutations can perturb either substrate accommodation or its interaction with complex partners. These insights provide a mechanistic basis for the enzyme’s dual role in intermediary metabolism and mitochondrial maintenance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, DHTKD1 is critical both for the regulation of lysine catabolism and for sustaining mitochondrial energy production. Disruption of its function—whether by genetic mutation or altered expression—links metabolic dysregulation with neurodegenerative phenotypes, thereby establishing DHTKD1 as a pivotal node in the interplay between metabolism and neurological function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yibo Wu, Evan G Williams, Sébastien Dubuis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.07.039"}], "href": "https://doi.org/10.1016/j.cell.2014.07.039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25215496"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25215496"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wang-Yang Xu, Yan Shen, Houbao Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "2-Aminoadipic acid protects against obesity and diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Endocrinol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/JOE-19-0157"}], "href": "https://doi.org/10.1530/JOE-19-0157"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31454789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31454789"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Katharina Danhauser, Sven W Sauer, Tobias B Haack, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.10.006"}], "href": "https://doi.org/10.1016/j.ajhg.2012.10.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23141293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23141293"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Wang-Yang Xu, Ming-Min Gu, Lian-Hua Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A nonsense mutation in DHTKD1 causes Charcot-Marie-Tooth disease type 2 in a large Chinese pedigree."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.09.018"}], "href": "https://doi.org/10.1016/j.ajhg.2012.09.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23141294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23141294"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wangyang Xu, Houbao Zhu, Mingmin Gu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DHTKD1 is essential for mitochondrial biogenesis and function maintenance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2013.08.047"}], "href": "https://doi.org/10.1016/j.febslet.2013.08.047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24076469"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24076469"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jacob Hagen, Heleen te Brinke, Ronald J A Wanders, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic basis of alpha-aminoadipic and alpha-ketoadipic aciduria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inherit Metab Dis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10545-015-9841-9"}], "href": "https://doi.org/10.1007/s10545-015-9841-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25860818"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25860818"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Dulce M Castro-Coyotl, Israel E Crisanto-López, Rosa M Hernández-Camacho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Atypical presentation of Charcot-Marie-Tooth disease type 2Q by mutations on DHTKD1 and NTRK2 genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bol Med Hosp Infant Mex (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.24875/BMHIM.21000016"}], "href": "https://doi.org/10.24875/BMHIM.21000016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34571524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34571524"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "João Leandro, Susmita Khamrui, Hui Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition and Crystal Structure of the Human DHTKD1-Thiamin Diphosphate Complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "ACS Chem Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acschembio.0c00114"}], "href": "https://doi.org/10.1021/acschembio.0c00114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32633484"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32633484"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "João Leandro, Tetyana Dodatko, Jan Aten, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DHTKD1 and OGDH display substrate overlap in cultured cells and form a hybrid 2-oxo acid dehydrogenase complex in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddaa037"}], "href": "https://doi.org/10.1093/hmg/ddaa037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32160276"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32160276"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Artem V Artiukhov, Aneta Grabarska, Ewelina Gumbarewicz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synthetic analogues of 2-oxo acids discriminate metabolic contribution of the 2-oxoglutarate and 2-oxoadipate dehydrogenases in mammalian cells and tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-58701-4"}], "href": "https://doi.org/10.1038/s41598-020-58701-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32024885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32024885"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Chun-Jie Luan, Wenting Guo, Lei Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CMT2Q-causing mutation in the Dhtkd1 gene lead to sensory defects, mitochondrial accumulation and altered metabolism in a knock-in mouse model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40478-020-00901-0"}], "href": "https://doi.org/10.1186/s40478-020-00901-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32169121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32169121"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Frank Jordan, Natalia Nemeria, Gary Gerfen "}, {"type": "b", "children": [{"type": "t", "text": "Human 2-Oxoglutarate Dehydrogenase and 2-Oxoadipate Dehydrogenase Both Generate Superoxide/H"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": "O"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " in a Side Reaction and Each Could Contribute to Oxidative Stress in Mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11064-019-02765-w"}], "href": "https://doi.org/10.1007/s11064-019-02765-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30847859"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30847859"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Gustavo A Bezerra, William R Foster, Henry J Bailey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "IUCrJ (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1107/S205225252000696X"}], "href": "https://doi.org/10.1107/S205225252000696X"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32695416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32695416"}]}]}]}
Synonyms	CMT2Q, AMOXAD
Proteins	DHTK1_HUMAN
NCBI Gene ID	55526
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DHTKD1 has 6,328 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 123 datasets.

Click the + buttons to view associations for DHTKD1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DHTKD1 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 DHTKD1 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 DHTKD1 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 DHTKD1 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 DHTKD1 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 DHTKD1 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 DHTKD1 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 DHTKD1 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 DHTKD1 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 DHTKD1 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 DHTKD1 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 DHTKD1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DHTKD1 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 DHTKD1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DHTKD1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DHTKD1 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 DHTKD1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DHTKD1 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 DHTKD1 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 DHTKD1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with DHTKD1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing DHTKD1 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 DHTKD1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DHTKD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DHTKD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing DHTKD1 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 DHTKD1 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 DHTKD1 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 DHTKD1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DHTKD1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DHTKD1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DHTKD1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DHTKD1 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 DHTKD1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving DHTKD1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving DHTKD1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DHTKD1 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 DHTKD1 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 DHTKD1 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 DHTKD1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DHTKD1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.