LDHD Gene

Name	lactate dehydrogenase D
Description	The protein encoded by this gene belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family. The similar protein in yeast has both D-lactate and D-glycerate dehydrogenase activities. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LDHD encodes a mitochondrial‐localized D‐lactate dehydrogenase that plays a central role in cellular metabolism by catalyzing the oxidation of d‐lactate into pyruvate. Alterations in LDHD function can therefore affect redox balance and energy homeostasis. For example, in humans a mutation within the catalytic site of LDHD has been linked to increased blood d‐lactate levels, which in turn drives compensatory renal uric acid reabsorption leading to hyperuricemia and gout."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, in hematopoietic stem cells the expression of LDHD—as well as that of other lactate dehydrogenase isoforms—is reduced following Cited2 deletion, suggesting that LDHD contributes to the regulation of glycolytic metabolism and is important for maintaining proper redox balance in these cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer cells, LDHD transcripts appear very low relative to the predominantly expressed LDHA and LDHB isoforms. In triple‐negative breast cancer cells, for instance, LDHD comprises only a minor fraction of total lactate dehydrogenase transcripts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, altered expression of LDHD has been observed in several disease settings. In kidney proteomic studies of hyperhomocysteinemia, LDHD was among proteins found to be down‐regulated"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and changes in its expression also accompany responses to traditional herbal treatments in gastric cancer models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Whole‐exome sequencing in pediatric patients with mitochondrial disease has further identified variants in LDHD, underscoring its clinical relevance in metabolic disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In livestock, differential expression of LDHD in peripheral blood mononuclear cells correlates with variations in metabolic processes between breeds"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and in glioma, decreased LDHD expression is negatively associated with markers of aggressive tumor behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, cases of d‐lactate acidosis accompanied by neurological manifestations have implicated deficiencies in d‐lactate dehydrogenase activity—presumably due to pathogenic variants in LDHD—as a contributing factor to disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, LDHD is critical for the oxidation of d‐lactate in mitochondria, and its proper function is essential for maintaining cellular metabolic balance. Its dysregulation or mutation can contribute to metabolic disturbances such as d‐lactate accumulation leading to hyperuricemia and gout, influence the metabolic profiles of stem cells and cancer cells, and be involved in broader pathophysiological conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Max Drabkin, Yuval Yogev, Lior Zeller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hyperuricemia and gout caused by missense mutation in d-lactate dehydrogenase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI129057"}], "href": "https://doi.org/10.1172/JCI129057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31638601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31638601"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jinwei Du, Qiang Li, Fangqiang Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cited2 is required for the maintenance of glycolytic metabolism in adult hematopoietic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells Dev (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/scd.2013.0370"}], "href": "https://doi.org/10.1089/scd.2013.0370"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24083546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24083546"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nzinga Mack, Elizabeth A Mazzio, David Bauer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stable shRNA Silencing of Lactate Dehydrogenase A (LDHA) in Human MDA-MB-231 Breast Cancer Cells Fails to Alter Lactic Acid Production, Glycolytic Activity, ATP or Survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21873/anticanres.11435"}], "href": "https://doi.org/10.21873/anticanres.11435"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28314283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28314283"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Joanna Suszyńska-Zajczyk, Olga Utyro, Hieronim Jakubowski "}, {"type": "b", "children": [{"type": "t", "text": "Methionine-induced hyperhomocysteinemia and bleomycin hydrolase deficiency alter the expression of mouse kidney proteins involved in renal disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2014.05.010"}], "href": "https://doi.org/10.1016/j.ymgme.2014.05.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24913063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24913063"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Min Fu, Yanju Liu, Huanbo Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Coptis chinensis and dried ginger herb combination inhibits gastric tumor growth by interfering with glucose metabolism via LDHA and SLC2A1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Ethnopharmacol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jep.2021.114771"}], "href": "https://doi.org/10.1016/j.jep.2021.114771"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34737010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34737010"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mandy H Y Tsang, Anna K Y Kwong, Kate L S Chan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Delineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genomics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40246-020-00278-0"}], "href": "https://doi.org/10.1186/s40246-020-00278-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32907636"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32907636"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "A Karthikeyan, Shalu Kumari Pathak, Amit Kumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selection and validation of differentially expressed metabolic and immune genes in weaned Ghurrah versus crossbred piglets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Trop Anim Health Prod (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11250-020-02440-1"}], "href": "https://doi.org/10.1007/s11250-020-02440-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33211188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33211188"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xin Jin, Zhen-Qing Sun, Gui-Liang Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Higher Expression of CDCA2 Associated with Poor Prognosis in Glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dis Markers (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2022/2184867"}], "href": "https://doi.org/10.1155/2022/2184867"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35386230"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35386230"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Anna Ka-Yee Kwong, Sheila Suet-Na Wong, Richard J T Rodenburg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human d-lactate dehydrogenase deficiency by "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "LDHD"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " mutation in a patient with neurological manifestations and mitochondrial complex IV deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JIMD Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jmd2.12220"}], "href": "https://doi.org/10.1002/jmd2.12220"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34258137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34258137"}]}]}]}
Synonyms	DLD
Proteins	LDHD_HUMAN
NCBI Gene ID	197257
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LDHD has 7,787 functional associations with biological entities spanning 9 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, sequence feature) extracted from 113 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

LDHD 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 LDHD 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 LDHD 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 LDHD 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 LDHD 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 LDHD 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 LDHD gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LDHD gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of LDHD gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LDHD 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 LDHD gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with LDHD protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LDHD 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 LDHD gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LDHD 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 LDHD 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 LDHD gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of LDHD gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing LDHD protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LDHD protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LDHD protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing LDHD 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 LDHD 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 LDHD 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 LDHD gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LDHD gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with LDHD gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with LDHD gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of LDHD 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 LDHD gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with LDHD 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 LDHD 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 LDHD 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 LDHD gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LDHD 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 LDHD 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 LDHD gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of LDHD 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 LDHD from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with LDHD gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with LDHD gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.