FLAD1

Chr 1AR

flavin adenine dinucleotide synthetase 1

ENSG00000160688 UniProt: Q8NFF5 OMIM: 610595

The enzyme catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD), an essential coenzyme for cellular metabolism, and also has FAD diphosphatase activity that breaks down FAD back to FMN. Mutations cause lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants, indicating its critical importance for normal cellular function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This enzyme has two activities: FAD diphosphatase activity and FAD synthase activity (PubMed:16643857, PubMed:21924249, PubMed:21951714, PubMed:23443125, PubMed:25135855, PubMed:26277395, PubMed:27259049, PubMed:31351152, PubMed:38688286). FAD diphosphatase acts on FAD and NADH to produce FMN and NMNH(2-), respectively (PubMed:26277395, PubMed:31351152, PubMed:38688286). FAD synthase catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme (PubMed:16643857, PubMed:21924249, PubMed:21951714, PubMed:23443125, PubMed:27259049, PubMed:38688286). In addition to its catalytic activities, the protein also facilitates the delivery of FAD to client apo-flavoproteins (PubMed:25954742). The balance between FAD synthesis and hydrolysis may be regulated by redox-sensing cysteine residues (PubMed:25135855, PubMed:26277395). At a much lower rate, FAD synthase catalyzes the reverse pyrophosphorolytic reaction (PubMed:21951714, PubMed:23443125, PubMed:25135855, PubMed:26277395). FAD synthase can also convert roseoflavin mononucleotide (RoFMN) to roseoflavin adenine dinucleotide (RoFAD); RoFMN is produced by riboflavin kinase when acting on the antibiotic roseoflavin (RoF) (PubMed:21924249). FAD synthase cannot convert 8-demethyl-8-amino-riboflavin mononucleotide (AFMN) to 8-demethyl-8-amino-riboflavin adenine dinucleotide (AFAD); AFMN is produced by riboflavin kinase when acting on the antibiotic 8-demethyl-8-amino-riboflavin (AF) (PubMed:21924249)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiencyMIM #255100

Clinical highlights

Gene-disease validity (ClinGen)

myopathy with abnormal lipid metabolism · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.59

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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