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

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 (8 variants)
• Multiple acyl-CoA dehydrogenase deficiency (8 variants)
• Myopathy with abnormal lipid metabolism (6 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	65		66
missense		3	103	13	2	121
nonsense	2	1	1	1		5
start loss			2			2
frameshift	11	2	1			14
inframe indel	1		2			3
splice donor/acceptor (+/-2bp)		2				2
splice region				2		2
non coding	1		8	31	8	48
Total	15	8	118	110	10

Highest pathogenic variant AF is 0.0000197

Variants in FLAD1

This is a list of pathogenic ClinVar variants found in the FLAD1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-154983391-C-T		not specified	Likely benign (Aug 02, 2017)
1-154983399-TGA-T		not specified	Likely benign (Feb 01, 2018)
1-154983668-A-G		not specified	Likely benign (Mar 06, 2018)
1-154983727-G-C			Uncertain significance (Jul 17, 2022)
1-154983729-G-A			Uncertain significance (Jan 12, 2024)
1-154983730-G-A			Likely benign (Oct 30, 2023)
1-154983747-G-A		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
1-154983767-G-C			Uncertain significance (Dec 26, 2021)
1-154983772-G-A			Likely benign (Oct 05, 2023)
1-154983779-G-T		Inborn genetic diseases	Uncertain significance (Nov 11, 2024)
1-154983791-G-A			Uncertain significance (Oct 17, 2022)
1-154983806-C-G			Uncertain significance (Jun 11, 2022)
1-154983814-C-G			Likely benign (Aug 09, 2022)
1-154983816-C-T			Uncertain significance (Mar 18, 2022)
1-154983822-G-A		Inborn genetic diseases	Uncertain significance (May 23, 2023)
1-154983824-C-T			Uncertain significance (Nov 18, 2022)
1-154983830-T-C			Uncertain significance (Apr 27, 2021)
1-154983851-A-T			Uncertain significance (May 30, 2022)
1-154983883-C-G			Likely benign (Jun 06, 2023)
1-154983892-T-C			Likely benign (Nov 24, 2023)
1-154983897-A-G			Uncertain significance (Nov 25, 2024)
1-154983901-G-C			Likely benign (Sep 24, 2022)
1-154983903-C-CA			Uncertain significance (Jan 05, 2022)
1-154983910-C-T			Likely benign (Jul 06, 2022)
1-154983926-C-T			Likely benign (Nov 10, 2023)

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

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