FLAD1 Gene - Flavin Adenine Dinucleotide Synthetase 1
Essential for FAD biosynthesis and mitochondrial function
Gene Information Card
| Symbol | FLAD1 |
|---|---|
| Full Name | Flavin Adenine Dinucleotide Synthetase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 80308 ncbi.nlm.nih.gov/gene/80308 |
| Ensembl ID | ENSG00000160613 |
| UniProt ID | Q8NFF5 |
| OMIM ID | 610595 |
| HGNC ID | 24671 |
| Aliases | FAD1, PP591, FADS, FLAD1A, FLAD1B |
Description
FLAD1 (Flavin Adenine Dinucleotide Synthetase 1) encodes the enzyme FAD synthetase (EC 2.7.7.2), which catalyzes the final step in the biosynthesis of flavin adenine dinucleotide (FAD) from riboflavin (vitamin B2) and ATP. FAD is an essential cofactor for numerous flavoprotein enzymes involved in mitochondrial electron transport, fatty acid oxidation, and amino acid metabolism. Alternative splicing produces two isoforms: a mitochondrial isoform (FLAD1A) and a cytosolic isoform (FLAD1B). Mutations in FLAD1 cause a form of lipid storage myopathy and multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric aciduria type II.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lipid storage myopathy due to FLAD1 deficiency | Loss-of-function mutations impair FAD synthesis, reducing activity of mitochondrial flavoenzymes and disrupting fatty acid beta-oxidation | PMID: 26875511, ClinVar |
| Multiple acyl-CoA dehydrogenase deficiency (MADD) | Deficient FAD leads to impaired function of multiple acyl-CoA dehydrogenases, causing accumulation of fatty acids and amino acid metabolites | PMID: 26875511, OMIM #610595 |
| Riboflavin-responsive MADD | Some FLAD1 mutations respond to high-dose riboflavin supplementation, partially restoring FAD levels | PMID: 26875511 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | Medium |
| Heart | 10.8 | Medium |
| Liver | 8.2 | Medium |
| Kidney | 6.4 | Low |
| Brain | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 9.5 | Hepatocellular carcinoma cell line |
| K562 | 7.2 | Chronic myelogenous leukemia |
| A549 | 6.8 | Lung carcinoma |
| HeLa | 5.4 | Cervical adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.745C>T (p.Arg249*) | Nonsense | Rare | Loss of function; truncation of FAD synthetase |
| c.1124G>A (p.Arg375Gln) | Missense | Rare | Reduced catalytic activity; associated with MADD |
| c.1580A>G (p.Tyr527Cys) | Missense | Rare | Impaired FAD binding; lipid storage myopathy |
Mutation functional classification
Loss of Function (LOF)
Most FLAD1 mutations are loss-of-function, leading to reduced FAD synthetase activity and impaired flavoprotein function.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Riboflavin metabolism (KEGG: hsa00740)
• Metabolic pathways (KEGG: hsa01100)
• Mitochondrial flavoprotein electron transport
Protein Summary
FAD synthetase (FLAD1) is a 587-amino acid enzyme that catalyzes the adenylation of FMN to form FAD. The mitochondrial isoform (FLAD1A) localizes to the mitochondrial matrix, while the cytosolic isoform (FLAD1B) is found in the cytoplasm. The enzyme contains a PAPS reductase domain and a MoCo oxidoreductase-like domain. Deficiency leads to reduced FAD levels, impairing the function of flavin-dependent dehydrogenases in mitochondria, resulting in metabolic myopathy and multi-systemic disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FLAD1 Knockout HEK293 Cell Line | EDJ-KQ2418 | Human | 80308 | Details Get a Quote |
| FLAD1 Knockout A-549 Cell Line | EDJ-KQ24294 | Human | 80308 | Details Get a Quote |
| FLAD1 Knockout HCT 116 Cell Line | EDJ-KQ24295 | Human | 80308 | Details Get a Quote |
| FLAD1 Knockout HeLa Cell Line | EDJ-KQ24296 | Human | 80308 | Details Get a Quote |
