BDH2 Gene

HGNC Family	Short chain dehydrogenase/reductase superfamily (SDR)
Name	3-hydroxybutyrate dehydrogenase, type 2
Description	Enables 3-hydroxybutyrate dehydrogenase activity and NAD binding activity. Involved in epithelial cell differentiation and fatty acid beta-oxidation. Located in cytosol. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BDH2 is a multifunctional cytosolic enzyme belonging to the short‐chain dehydrogenase/reductase family that plays diverse roles in cellular metabolism and homeostasis. In its canonical function, BDH2 catalyzes the NAD⁺‐dependent conversion of (R)‑3‐hydroxybutyrate to acetoacetate, thereby participating in cytosolic ketone body utilization—a role that is particularly relevant when alternative energy substrates are considered under ketogenic conditions, as shown in studies of neuronal and glioma cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, BDH2 is the rate‐limiting enzyme in the biosynthesis of a mammalian siderophore (2,5‐dihydroxybenzoic acid), which mediates intracellular iron trafficking and homeostasis. Through siderophore production, BDH2 helps to regulate both iron distribution and redox balance, with dysregulation leading to aberrant iron accumulation or depletion in various tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, BDH2 exhibits context‐dependent roles. In several solid tumors—including gastric cancer, hepatocellular carcinoma, and clear cell renal cell carcinoma—reduced BDH2 expression is associated with impaired apoptosis, enhanced proliferation, and poorer clinical outcomes; ectopic BDH2 expression in these settings can trigger mitochondrial apoptosis and autophagy via modulation of intracellular reactive oxygen species and signaling pathways such as Keap1/Nrf2 and PI3K/Akt, thereby acting as a tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " Conversely, in acute myeloid leukemia BDH2 displays an anti‐apoptotic effect and its higher expression portends a poor prognosis, while in pancreatic and esophageal cancers, BDH2 expression (often regulated via lncRNA-mediated pathways) promotes cell proliferation and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that BDH2 functions at the nexus of ketone metabolism, iron homeostasis, and cellular stress responses. Its dual roles in metabolic adaptation and regulation of intracellular iron not only influence normal physiological processes but also impact tumor progression and the cellular response to inflammation. As such, BDH2 represents a potential prognostic biomarker and therapeutic target in a range of diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gabriele D Maurer, Daniel P Brucker, Oliver Bähr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-11-315"}], "href": "https://doi.org/10.1186/1471-2407-11-315"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21791085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21791085"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kunde Guo, Petra Lukacik, Evangelos Papagrigoriou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of human DHRS6, an orphan short chain dehydrogenase/reductase enzyme: a novel, cytosolic type 2 R-beta-hydroxybutyrate dehydrogenase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M511346200"}], "href": "https://doi.org/10.1074/jbc.M511346200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16380372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16380372"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhuoming Liu, Alieta Ciocea, L Devireddy "}, {"type": "b", "children": [{"type": "t", "text": "Endogenous siderophore 2,5-dihydroxybenzoic acid deficiency promotes anemia and splenic iron overload in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00231-14"}], "href": "https://doi.org/10.1128/MCB.00231-14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24777603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24777603"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sudha Ananth, Jaya P Gnana-Prakasam, Yangzom D Bhutia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the cholesterol efflux transporters ABCA1 and ABCG1 in retina in hemochromatosis and by the endogenous siderophore 2,5-dihydroxybenzoic acid."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2014.01.010"}], "href": "https://doi.org/10.1016/j.bbadis.2014.01.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24462739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24462739"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Susu M Zughaier, Brandon B Stauffer, Nael A McCarty "}, {"type": "b", "children": [{"type": "t", "text": "Inflammation and ER stress downregulate BDH2 expression and dysregulate intracellular iron in macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2014/140728"}], "href": "https://doi.org/10.1155/2014/140728"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25762501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25762501"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jia-Zhou Liu, Yi-Lin Hu, Ying Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-020-01620-z"}], "href": "https://doi.org/10.1186/s13046-020-01620-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32605589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32605589"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wanmeng Cui, Wenqi Luo, Xiaohui Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Oncol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fonc.2019.01422"}], "href": "https://doi.org/10.3389/fonc.2019.01422"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31921677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31921677"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nan Aa, Jia-Hua Guo, Bei Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Compound danshen dripping pills normalize a reprogrammed metabolism of myocardial ischemia rats to interpret its time-dependent efficacy in clinic trials: a metabolomic study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metabolomics (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11306-019-1577-3"}], "href": "https://doi.org/10.1007/s11306-019-1577-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31541307"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31541307"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Wen-Chi Yang, Wan-Chi Tsai, Pai-Mei Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human BDH2, an anti-apoptosis factor, is a novel poor prognostic factor for de novo cytogenetically normal acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biomed Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1423-0127-20-58"}], "href": "https://doi.org/10.1186/1423-0127-20-58"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23941109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23941109"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Wenqiao Zang, Tao Wang, Yuanyuan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of long non-coding RNA TP73-AS1 inhibits cell proliferation and induces apoptosis in esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.6963"}], "href": "https://doi.org/10.18632/oncotarget.6963"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26799587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26799587"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xian-Ping Cui, Chuan-Xi Wang, Zhi-Yi Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA TP73-AS1 sponges miR-141-3p to promote the migration and invasion of pancreatic cancer cells through the up-regulation of BDH2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20181937"}], "href": "https://doi.org/10.1042/BSR20181937"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30643007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30643007"}]}]}]}
Synonyms	DHRS6, UNQ6308, PRO20933, SDR15C1, UCPA-OR
Proteins	BDH2_HUMAN
NCBI Gene ID	56898
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

BDH2 has 5,718 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 112 datasets.

Click the + buttons to view associations for BDH2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

BDH2 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 BDH2 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 BDH2 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 BDH2 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 BDH2 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 BDH2 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 BDH2 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 BDH2 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 BDH2 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 BDH2 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 BDH2 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 BDH2 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 BDH2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with BDH2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with BDH2 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 BDH2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of BDH2 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 BDH2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of BDH2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing BDH2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with BDH2 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 BDH2 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 BDH2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with BDH2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with BDH2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with BDH2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of BDH2 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 BDH2 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 BDH2 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 BDH2 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 BDH2 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 BDH2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with BDH2 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 BDH2 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 BDH2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of BDH2 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 BDH2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with BDH2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of BDH2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with BDH2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing BDH2 from the GeneSigDB Published Gene Signatures dataset.