FLAD1

flavin adenine dinucleotide synthetase 1

Basic information

Region (hg38): 1:154983338-154993111

Links

ENSG00000160688

∙ NCBI:80308 ∙ OMIM:610595 ∙ HGNC:24671 ∙ Uniprot:Q8NFF5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

myopathy with abnormal lipid metabolism (Moderate), mode of inheritance: AR
myopathy with abnormal lipid metabolism (Strong), mode of inheritance: AR
myopathy with abnormal lipid metabolism (Moderate), mode of inheritance: AR
myopathy with abnormal lipid metabolism (Definitive), mode of inheritance: AR
myopathy with abnormal lipid metabolism (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lipid storage myopathy due to FLAD1 deficiency	AR	Biochemical; Cardiovascular	Individuals have shown clinical improvement with dietary management (riboflavin); The condition has been described with cardiomyopathy, and awareness may allow prompt diagnosis and management (eg, with medical management and ICD)	Biochemical; Cardiovascular; Neurologic	25058219; 27259049

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FLAD1 gene.

not_provided (261 variants)
Inborn_genetic_diseases (70 variants)
Myopathy_with_abnormal_lipid_metabolism (16 variants)
FLAD1-related_disorder (10 variants)
Multiple_acyl-CoA_dehydrogenase_deficiency (10 variants)
not_specified (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FLAD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000025207.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	81 clinvar	1 clinvar	83
missense	1 clinvar	1 clinvar	147 clinvar	14 clinvar		163
nonsense	6 clinvar	1 clinvar	1 clinvar			8
start loss						0
frameshift	12 clinvar	3 clinvar	1 clinvar			16
splice donor/acceptor (+/-2bp)		4 clinvar				4
Total	19	9	150	95	1

Highest pathogenic variant AF is 0.000024163568

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FLAD1	protein_coding	protein_coding	ENST00000292180	7	9774

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00936	0.990	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.581	306	336	0.911	0.0000190	3728
Missense in Polyphen		92	103.66	0.88755		1144
Synonymous	1.72	111	137	0.812	0.00000702	1273
Loss of Function	3.07	8	24.4	0.328	0.00000131	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000416	0.000416
Ashkenazi Jewish	0.000202	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.0000544	0.0000544
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme. {ECO:0000269|PubMed:16643857, ECO:0000269|PubMed:27259049}.;
Disease: DISEASE: Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency (LSMFLAD) [MIM:255100]: An autosomal recessive, inborn error of metabolism characterized by variable mitochondrial dysfunction. Clinical features range from severe cardiac and respiratory insufficiency with onset in infancy and resulting in early death, to mild muscle weakness with onset in adulthood. Some patients show significant improvement with riboflavin treatment. Analysis of skeletal muscle show multiple mitochondrial respiratory chain deficiency and a lipid storage myopathy in most patients. {ECO:0000269|PubMed:27259049}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Riboflavin metabolism - Homo sapiens (human);Riboflavin Metabolism;Selenium Micronutrient Network;Folate Metabolism;Metabolism;Vitamin B2 (riboflavin) metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;flavin biosynthesis (Consensus)

Recessive Scores

pRec: 0.232

Intolerance Scores

loftool: 0.0672
rvis_EVS: -1.04
rvis_percentile_EVS: 7.71

Haploinsufficiency Scores

pHI: 0.114
hipred: N
hipred_score: 0.371
ghis: 0.639

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.999

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Flad1
Phenotype

Gene ontology

Biological process: FAD biosynthetic process;riboflavin metabolic process
Cellular component: mitochondrial matrix;cytosol;plasma membrane
Molecular function: FMN adenylyltransferase activity;protein binding;ATP binding