FLAD1

Chr 1AR

flavin adenine dinucleotide synthetase 1

Also known as: FAD1, FADS, LSMFLAD, PP591

NCBI Gene: 80308 ENSG00000160688 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 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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.591 OMIM phenotype

Clinical Summary— FLAD1

🧬

Gene-Disease Validity (ClinGen)

myopathy with abnormal lipid metabolism · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.009

Z-score 3.07

OE 0.33 (0.19–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.58Z-score

OE missense 0.91 (0.83–1.00)

306 obs / 336.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.19–0.59)

0≤0.351.4

Missense OE?0.91 (0.83–1.00)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 8 / 24.4Missense obs/exp: 306 / 336.0Syn Z: 1.72

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveFLAD1-related riboflavin-responsive and non-responsive multiple acyl-CoA dehydrogenase and combined respiratory-chain deficiencyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6842th %ile

GOF

0.5758th %ile

LOF

0.3551th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.