FLAD1 Gene

Name	flavin adenine dinucleotide synthetase 1
Description	This gene encodes the enzyme that catalyzes adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FLAD1 encodes the bifunctional enzyme FAD synthase (FADS), which catalyzes the final step in converting riboflavin into the redox cofactor flavin adenine dinucleotide (FAD). FAD is essential for the function of numerous flavoproteins that drive mitochondrial energy production and diverse metabolic processes. FLAD1‐derived FADS exists in multiple isoforms with distinct features; for example, one isoform contains a mitochondrial targeting sequence that directs it to mitochondria, whereas others remain cytosolic. Detailed biochemical investigations have demonstrated that the enzyme comprises two functional domains: a C‐terminal domain responsible for FAD synthesis (and, under certain conditions, catalyzing pyrophosphorolysis) and an N‐terminal molybdopterin‐binding–like domain that, in some cases, exhibits FAD hydrolytic activity. Together these domains ensure tight regulation of cellular FAD homeostasis (see, for example."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Pathogenic variants in FLAD1, including biallelic frameshift mutations in the N‐terminal domain and missense mutations within the catalytic FADS domain, have been linked to multiple acyl‐CoA dehydrogenation deficiency (MADD). This mitochondrial fatty acid oxidation disorder can manifest with a spectrum of clinical severity ranging from severe neonatal disease to milder, riboflavin‐responsive forms detectable by newborn screening. Such defects underscore the central role of FLAD1 in sustaining respiratory‐chain activity and overall cellular metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additionally, emerging studies indicate that FLAD1’s function extends beyond basic cofactor synthesis. Alterations in its activity have been associated with changes in cellular growth and regulatory pathways, including potential roles in cancer cell proliferation. Such findings highlight the broader impact of maintaining proper flavin homeostasis on cell physiology."}, {"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, the development of optimized recombinant expression and purification protocols for the various human FADS isoforms has provided essential tools for kinetic and molecular characterization. These advances contribute to a deeper understanding of FLAD1’s multifaceted roles in both FAD synthesis and regulation, and they may aid in the design of targeted therapies for related metabolic disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rikke K J Olsen, Eliška Koňaříková, Teresa A Giancaspero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2016.04.006"}], "href": "https://doi.org/10.1016/j.ajhg.2016.04.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27259049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27259049"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carmen Brizio, Michele Galluccio, Robin Wait, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2006.04.003"}], "href": "https://doi.org/10.1016/j.bbrc.2006.04.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16643857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16643857"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Teresa Anna Giancaspero, Michele Galluccio, Angelica Miccolis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human FAD synthase is a bi-functional enzyme with a FAD hydrolase activity in the molybdopterin binding domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2015.08.035"}], "href": "https://doi.org/10.1016/j.bbrc.2015.08.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26277395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26277395"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Piero Leone, Michele Galluccio, Carmen Brizio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The hidden side of the human FAD synthase 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Macromol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ijbiomac.2019.07.138"}], "href": "https://doi.org/10.1016/j.ijbiomac.2019.07.138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31351152"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31351152"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kai Muru, Karit Reinson, Kadi Künnapas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FLAD1-associated multiple acyl-CoA dehydrogenase deficiency identified by newborn screening."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomic Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mgg3.915"}], "href": "https://doi.org/10.1002/mgg3.915"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31392824"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31392824"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "B Ryder, M Tolomeo, Z Nochi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Novel Truncating FLAD1 Variant, Causing Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) in an 8-Year-Old Boy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JIMD Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/8904_2018_139"}], "href": "https://doi.org/10.1007/8904_2018_139"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30311138"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30311138"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kenji Yamada, Michinori Ito, Hironori Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Flavin adenine dinucleotide synthase deficiency due to FLAD1 mutation presenting as multiple acyl-CoA dehydrogenation deficiency-like disease: A case report."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Dev (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.braindev.2019.04.002"}], "href": "https://doi.org/10.1016/j.braindev.2019.04.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30982706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30982706"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Piero Leone, Maria Tolomeo, Maria Barile "}, {"type": "b", "children": [{"type": "t", "text": "Continuous and Discontinuous Approaches to Study FAD Synthesis and Degradation Catalyzed by Purified Recombinant FAD Synthase or Cellular Fractions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Methods Mol Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-1-0716-1286-6_7"}], "href": "https://doi.org/10.1007/978-1-0716-1286-6_7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33751431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33751431"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Ke Cheng, Jun-Seok Lee, Piliang Hao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tetrazole-Based Probes for Integrated Phenotypic Screening, Affinity-Based Proteome Profiling, and Sensitive Detection of a Cancer Biomarker."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Angew Chem Int Ed Engl (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/anie.201709584"}], "href": "https://doi.org/10.1002/anie.201709584"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28967196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28967196"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Enza Maria Torchetti, Carmen Brizio, Matilde Colella, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial localization of human FAD synthetase isoform 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mitochondrion (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mito.2009.12.149"}], "href": "https://doi.org/10.1016/j.mito.2009.12.149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20060505"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20060505"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Michele Galluccio, Cesare Indiveri "}, {"type": "b", "children": [{"type": "t", "text": "Heterologous Overexpression of Human FAD Synthase Isoforms 1 and 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Methods Mol Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-1-0716-1286-6_5"}], "href": "https://doi.org/10.1007/978-1-0716-1286-6_5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33751429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33751429"}]}]}]}
Synonyms	PP591, LSMFLAD
Proteins	FAD1_HUMAN
NCBI Gene ID	80308
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

FLAD1 has 5,654 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 118 datasets.

Click the + buttons to view associations for FLAD1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

FLAD1 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 FLAD1 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 FLAD1 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 FLAD1 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 FLAD1 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 FLAD1 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 FLAD1 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 FLAD1 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 FLAD1 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 FLAD1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of FLAD1 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 FLAD1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with FLAD1 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of FLAD1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of FLAD1 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 FLAD1 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 FLAD1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of FLAD1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing FLAD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing FLAD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing FLAD1 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 FLAD1 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 FLAD1 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 FLAD1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with FLAD1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with FLAD1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with FLAD1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of FLAD1 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 FLAD1 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 FLAD1 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 FLAD1 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 FLAD1 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 FLAD1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with FLAD1 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 FLAD1 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 FLAD1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of FLAD1 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 FLAD1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of FLAD1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with FLAD1 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 FLAD1 from the GeneSigDB Published Gene Signatures dataset.