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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
FLAD1
flavin adenine dinucleotide synthetase 1
Chromosome 1 Β· 1q21.3
NCBI Gene: 80308Ensembl: ENSG00000160688.20HGNC: HGNC:24671UniProt: Q8NFF5
66PubMed Papers
21Diseases
0Drugs
30Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitochondrial matrixcytosolFMN adenylyltransferase activityidentical protein bindingmyopathy with abnormal lipid metabolismmultiple acyl-CoA dehydrogenase deficiency, severe neonatal typemultiple acyl-CoA dehydrogenase deficiency, mild typemultiple acyl-CoA dehydrogenase deficiency
✦AI Summary

FLAD1 encodes flavin adenine dinucleotide synthetase 1, an enzyme essential for riboflavin metabolism and FAD homeostasis. The protein exhibits dual enzymatic activities: FAD synthase activity that catalyzes the adenylation of flavin mononucleotide (FMN) to form FAD coenzyme, and FAD diphosphatase activity that hydrolyzes FAD to FMN 1. Beyond its catalytic functions, FLAD1 facilitates the delivery of FAD to client apo-flavoproteins and its enzymatic balance may be regulated by redox-sensing cysteine residues 1. The enzyme is crucial for cellular bioenergetics, redox homeostasis, DNA repair, and chr1 remodeling through its role in flavocoenzyme biosynthesis 1. Biallelic FLAD1 mutations cause FAD synthase deficiency, leading to lipid storage myopathy with multiple acyl-CoA dehydrogenation deficiency (MADD), which responds to riboflavin supplementation 21. FLAD1 expression is increased in various cancers, including breast cancer and hepatocellular carcinoma, where it promotes tumor progression through metabolic reprogramming 34. In triple-negative breast cancer, FLAD1 amplification enhances FAD-dependent lysine demethylase 1 activity, promoting lipid biosynthesis pathways crucial for cancer progression 3.

Sources cited
1
FLAD1 exhibits FAD synthase and diphosphatase activities, facilitates FAD delivery to flavoproteins, and its deficiency causes lipid storage myopathy
PMID: 30680745
2
FLAD1 mutations cause riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency with lipid storage myopathy
PMID: 38228875
3
FLAD1 copy number amplification promotes triple-negative breast cancer progression through FAD-dependent metabolic reprogramming
PMID: 39890808
4
FLAD1 is overexpressed in various cancers, particularly breast cancer, with diagnostic and prognostic significance
PMID: 34336008
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
myopathy with abnormal lipid metabolismOpen Targets
0.77Strong
multiple acyl-CoA dehydrogenase deficiency, mild typeOpen Targets
0.64Moderate
multiple acyl-CoA dehydrogenase deficiency, severe neonatal typeOpen Targets
0.64Moderate
multiple acyl-CoA dehydrogenase deficiencyOpen Targets
0.53Moderate
glutaric aciduriaOpen Targets
0.52Moderate
neurodegenerative diseaseOpen Targets
0.50Moderate
osteoarthritisOpen Targets
0.24Weak
genetic disorderOpen Targets
0.19Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
cancerOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.07Suggestive
asthmaOpen Targets
0.04Suggestive
type 2 diabetes mellitusOpen Targets
0.04Suggestive
metabolic syndromeOpen Targets
0.03Suggestive
atopic eczemaOpen Targets
0.03Suggestive
Alzheimer diseaseOpen Targets
0.03Suggestive
Abnormality of limbsOpen Targets
0.02Suggestive
Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiencyUniProt
Pathogenic Variants30
NM_025207.5(FLAD1):c.1588C>T (p.Arg530Cys)Pathogenic
Multiple acyl-CoA dehydrogenase deficiency|Myopathy with abnormal lipid metabolism|not provided|FLAD1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 530
NM_025207.5(FLAD1):c.745C>T (p.Arg249Ter)Pathogenic
Multiple acyl-CoA dehydrogenase deficiency|not provided|Myopathy with abnormal lipid metabolism
β˜…β˜…β˜†β˜†2025β†’ Residue 249
NM_025207.5(FLAD1):c.408C>A (p.Cys136Ter)Pathogenic
not provided|Myopathy with abnormal lipid metabolism
β˜…β˜…β˜†β˜†2025β†’ Residue 136
NM_025207.5(FLAD1):c.442C>T (p.Arg148Ter)Pathogenic
Myopathy with abnormal lipid metabolism
β˜…β˜…β˜†β˜†2023β†’ Residue 148
NM_025207.5(FLAD1):c.401_404del (p.Phe134fs)Pathogenic
Myopathy with abnormal lipid metabolism|Multiple acyl-CoA dehydrogenase deficiency
β˜…β˜…β˜†β˜†2016β†’ Residue 134
NM_025207.5(FLAD1):c.1090G>T (p.Glu364Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 364
NM_025207.5(FLAD1):c.390dup (p.Asn131fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 131
NM_025207.5(FLAD1):c.1475del (p.Asp492fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 492
NM_025207.5(FLAD1):c.1364+1_1364+3delLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_025207.5(FLAD1):c.1375C>T (p.Gln459Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 459
NM_025207.5(FLAD1):c.1266-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_025207.5(FLAD1):c.373-3C>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_025207.5(FLAD1):c.1555-1G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_025207.5(FLAD1):c.811del (p.Leu271fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 271
NM_025207.5(FLAD1):c.1117+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_025207.5(FLAD1):c.987_988insC (p.Glu330fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 330
NM_025207.5(FLAD1):c.1339C>T (p.Gln447Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 447
NM_025207.5(FLAD1):c.796del (p.Glu266fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 266
NM_025207.5(FLAD1):c.708C>A (p.Cys236Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 236
NM_025207.5(FLAD1):c.1054_1075del (p.Val352fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 352
View on ClinVar β†—
Related Genes
H2AZ1Protein interaction100%EEF1A1Protein interaction99%SDHAProtein interaction92%ENPP3Protein interaction91%ACP5Protein interaction90%ENPP1Protein interaction90%
Tissue Expression6 tissues
Liver
100%
Lung
72%
Heart
64%
Brain
59%
Ovary
52%
Bone Marrow
45%
Gene Interaction Network
Click a node to explore
FLAD1H2AZ1EEF1A1SDHAENPP3ACP5ENPP1
PROTEIN STRUCTURE
Preparing viewer…
PDB8ROM Β· 1.69 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.81LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.61 [0.47–0.81]
RankingsWhere FLAD1 stands among ~20K protein-coding genes
  • #7,066of 20,598
    Most Researched66
  • #1,811of 5,498
    Most Pathogenic Variants30
  • #6,784of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedFLAD1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
1.00
2
Involvement of muscle satellite cell dysfunction in neuromuscular disorders: Expanding the portfolio of satellite cell-opathies.
PMID: 35302338
Eur J Transl Myol Β· 2022
0.90
3
Copy number amplification of FLAD1 promotes the progression of triple-negative breast cancer through lipid metabolism.
PMID: 39890808
Nat Commun Β· 2025
0.80
4
A comparative study on riboflavin responsive multiple acyl-CoA dehydrogenation deficiency due to variants in FLAD1 and ETFDH gene.
PMID: 38228875
J Hum Genet Β· 2024
0.70
5
Disorders of riboflavin metabolism.
PMID: 30680745
J Inherit Metab Dis Β· 2019
0.60