FLAD1

Chr 1AR

flavin adenine dinucleotide synthetase 1

Also known as: FAD1, FADS, LSMFLAD, PP591

NCBI Gene: 80308ENSG00000160688UniProt: Q8NFF5OMIM: 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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
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.
📋
ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 168 VUS of 389 total submissions
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

opentargets: TimeoutError: The operation was aborted due to timeout

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 OE0.33 (0.19–0.59)
0≤0.351.4
Missense OE0.91 (0.83–1.00)
0≤0.61.4
Synonymous OE0.81
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

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

DN
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.

ClinVar Variant Classifications

389 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic14
VUS168
Likely Benign141
Benign14
Conflicting10
29
Pathogenic
14
Likely Pathogenic
168
VUS
141
Likely Benign
14
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
1
11
0
29
Likely Pathogenic
9
3
2
0
14
VUS
2
159
7
0
168
Likely Benign
0
13
36
92
141
Benign
0
0
13
1
14
Conflicting
—10
Total281766993376

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FLAD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Detection of FLAD1 mutations and lipid storage myopathy in a 5-year-old boy: a case report study
Hosseini SA et al.·Ann Med Surg (Lond)
2023Case report
OGT and FLAD1 Genes Had Significant Prognostic Roles in Progressive Pathogenesis in Prostate Cancer
Kim SH et al.·World J Mens Health
2023
Significant Diagnostic and Prognostic Value of FLAD1 and Related MicroRNAs in Breast Cancer after a Pan-Cancer Analysis
Mei M et al.·Dis Markers
2021
An increased demand of FAD synthesis in Differentiated and Stem Pancreatic Cancer Cells is accomplished by modulating FLAD1 gene expression.
Nisco A et al.·FEBS J
2023
Infant with early onset bilateral facial and bulbar weakness: Successful treatment of riboflavin in multiple acyl-CoA dehydrogenase deficiency caused by biallelic nonsense FLAD1 variants.
Lee YJ et al.·Neuromuscul Disord
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients