HIBADH Gene

Name	3-hydroxyisobutyrate dehydrogenase
Description	This gene encodes a mitochondrial 3-hydroxyisobutyrate dehydrogenase enzyme. The encoded protein plays a critical role in the catabolism of L-valine by catalyzing the oxidation of 3-hydroxyisobutyrate to methylmalonate semialdehyde. [provided by RefSeq, Nov 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n 3‐Hydroxyisobutyrate dehydrogenase (HIBADH) is a NAD⁺‐dependent enzyme that catalyzes the oxidation of L‐3‐hydroxyisobutyrate to methylmalonate semialdehyde as part of the valine catabolic pathway. In addition to its well‐established metabolic role, altered HIBADH activity has been implicated in human metabolic disorders such as 3‐hydroxyisobutyric aciduria, although studies report heterogeneous findings – with some patients exhibiting normal enzyme activity in fibroblasts and others showing pathogenic variants associated with the disorder."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In reproductive biology, proteomic analyses of human spermatozoa have demonstrated that HIBADH is specifically localized to the mid-piece – a mitochondria-rich region – and that its enzymatic activity correlates with sperm motility, suggesting its involvement in maintaining mitochondrial function and energy production in sperm."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Structural and mutational studies in various organisms have highlighted the critical importance of conserved cysteine residues (e.g., Cys‐210 in Mycobacterium tuberculosis and Cys‐215 in rat HIBADH) for the enzyme’s catalytic function and for maintaining proper conformation of substrate–entry loops."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, genomic analyses have revealed that the Hibadh gene lies within a conserved regulatory landscape; a highly conserved noncoding sequence located in one of its introns is associated with coordinated expression in distal limb and genital tissues, suggesting that beyond its metabolic function, HIBADH might be co‐regulated with genes critical for developmental processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jörn Oliver Sass, Melanie Walter, Julian P H Shield, et al. "}, {"type": "b", "children": [{"type": "t", "text": "3-Hydroxyisobutyrate aciduria and mutations in the ALDH6A1 gene coding for methylmalonate semialdehyde dehydrogenase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inherit Metab Dis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10545-011-9381-x"}], "href": "https://doi.org/10.1007/s10545-011-9381-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21863277"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21863277"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ference J Loupatty, Annemarie van der Steen, Lodewijk Ijlst, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical, biochemical, and molecular findings in three patients with 3-hydroxyisobutyric aciduria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2005.09.019"}], "href": "https://doi.org/10.1016/j.ymgme.2005.09.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16466957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16466957"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Florin Sasarman, Sacha Ferdinandusse, David S Sinasac, et al. "}, {"type": "b", "children": [{"type": "t", "text": "3-Hydroxyisobutyric acid dehydrogenase deficiency: Expanding the clinical spectrum and quantitation of D- and L-3-Hydroxyisobutyric acid by an LC-MS/MS method."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inherit Metab Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jimd.12486"}], "href": "https://doi.org/10.1002/jimd.12486"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35174513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35174513"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yung-Chieh Tasi, Hsin-Chih Albert Chao, Chia-Ling Chung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of 3-hydroxyisobutyrate dehydrogenase, HIBADH, as a sperm-motility marker."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-013-9954-8"}], "href": "https://doi.org/10.1007/s10815-013-9954-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23423614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23423614"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Amrita Singh, Nagendar Goud Badepally, Avadhesha Surolia "}, {"type": "b", "children": [{"type": "t", "text": "Role of a cysteine residue in substrate entry and catalysis in MtHIBADH: Analysis by chemical modifications and site-directed mutagenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "IUBMB Life (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/iub.2466"}], "href": "https://doi.org/10.1002/iub.2466"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33724683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33724683"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "J W Hawes, D W Crabb, R M Chan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chemical modification and site-directed mutagenesis studies of rat 3-hydroxyisobutyrate dehydrogenase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (1995)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi00013a012"}], "href": "https://doi.org/10.1021/bi00013a012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "7703236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/7703236"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jessica A Lehoczky, Melissa E Williams, Jeffrey W Innis "}, {"type": "b", "children": [{"type": "t", "text": "Conserved expression domains for genes upstream and within the HoxA and HoxD clusters suggests a long-range enhancer existed before cluster duplication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Evol Dev (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1525-142X.2004.04050.x"}], "href": "https://doi.org/10.1111/j.1525-142X.2004.04050.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15509224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15509224"}]}]}]}
Synonyms	NS5ATP1
Proteins	3HIDH_HUMAN
NCBI Gene ID	11112
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HIBADH has 6,142 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 126 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

HIBADH 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 HIBADH 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 HIBADH gene relative to other tissues from the Allen Brain Atlas Adult Human 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 HIBADH 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 HIBADH 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 HIBADH 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 HIBADH 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 HIBADH 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 HIBADH 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 HIBADH 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 HIBADH gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HIBADH protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HIBADH 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 HIBADH gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HIBADH 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 HIBADH gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HIBADH protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HIBADH protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing HIBADH 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 HIBADH 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 HIBADH 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 HIBADH 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 HIBADH gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HIBADH gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HIBADH gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HIBADH gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HIBADH gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of HIBADH 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 HIBADH 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 HIBADH 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 HIBADH 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 HIBADH 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 HIBADH gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HIBADH gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for HIBADH protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HIBADH 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 HIBADH gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HIBADH 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 HIBADH from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with HIBADH gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with HIBADH gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.