FLAD1 (flavin adenine dinucleotide synthetase 1)

Gene

• Entrez ID: 80308
• Gene name: Flavin adenine dinucleotide synthetase 1
• Gene symbol: FLAD1
• Synonyms (NCBI Gene): FAD1, FADS, LSMFLAD, PP591
• Chromosome: 1
• Chromosome location: 1q21.3
• Summary: 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 20

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs142224458	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, coding sequence variant, genic downstream transcript variant
rs199979286	C>T	Pathogenic	Stop gained, coding sequence variant
rs876661309	CCT>-	Pathogenic	Coding sequence variant, inframe deletion, genic downstream transcript variant
rs876661310	->GC	Pathogenic	Coding sequence variant, frameshift variant
rs876661311	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs876661312	GCAGGGGGCATC>CA	Pathogenic	Coding sequence variant, frameshift variant
rs876661313	TTCT>-	Pathogenic	Coding sequence variant, frameshift variant
rs876661314	G>-	Pathogenic	Coding sequence variant, frameshift variant, 5 prime UTR variant
rs876661315	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1057518160	C>A	Pathogenic	Stop gained, coding sequence variant
rs1170313629	GTCCCCTACATGCCCAACGCTG>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1571488364	TGAGGGCAGC>-	Likely-pathogenic	Coding sequence variant, frameshift variant, genic downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT027748	hsa-miR-98-5p	Microarray	19088304
MIRT032427	hsa-let-7b-5p	Proteomics	18668040
MIRT032427	hsa-let-7b-5p	CLASH	23622248
MIRT044739	hsa-miR-320a	CLASH	23622248
MIRT037007	hsa-miR-877-3p	CLASH	23622248
MIRT736650	hsa-let-7b-3p	Microarray	32824926
MIRT998174	hsa-miR-1266	CLIP-seq
MIRT998175	hsa-miR-1286	CLIP-seq
MIRT998176	hsa-miR-1913	CLIP-seq
MIRT998177	hsa-miR-3182	CLIP-seq
MIRT998178	hsa-miR-324-3p	CLIP-seq
MIRT998179	hsa-miR-3664-3p	CLIP-seq
MIRT998180	hsa-miR-4270	CLIP-seq
MIRT998181	hsa-miR-4290	CLIP-seq
MIRT998182	hsa-miR-4441	CLIP-seq
MIRT998183	hsa-miR-4518	CLIP-seq
MIRT998184	hsa-miR-4722-5p	CLIP-seq
MIRT998185	hsa-miR-4727-5p	CLIP-seq
MIRT998186	hsa-miR-4729	CLIP-seq
MIRT998187	hsa-miR-7	CLIP-seq
MIRT2229834	hsa-miR-204	CLIP-seq
MIRT2229835	hsa-miR-211	CLIP-seq
MIRT2229836	hsa-miR-3938	CLIP-seq
MIRT2229837	hsa-miR-4755-5p	CLIP-seq
MIRT2229838	hsa-miR-623	CLIP-seq
MIRT2229839	hsa-miR-660	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003824	Function	Catalytic activity	IEA
GO:0003919	Function	FMN adenylyltransferase activity	IBA
GO:0003919	Function	FMN adenylyltransferase activity	IDA	20060505, 21951714, 38688286
GO:0003919	Function	FMN adenylyltransferase activity	IEA
GO:0003919	Function	FMN adenylyltransferase activity	TAS
GO:0005515	Function	Protein binding	IPI	25416956, 31515488, 32296183, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IDA	20060505
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005829	Component	Cytosol	IDA	20060505
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0006747	Process	FAD biosynthetic process	IBA
GO:0006747	Process	FAD biosynthetic process	IDA	20060505
GO:0006747	Process	FAD biosynthetic process	IEA
GO:0006771	Process	Riboflavin metabolic process	IEA
GO:0006771	Process	Riboflavin metabolic process	TAS
GO:0016740	Function	Transferase activity	IEA
GO:0016779	Function	Nucleotidyltransferase activity	IEA
GO:0042802	Function	Identical protein binding	IPI	16189514, 25416956, 31515488, 32296183
GO:0047884	Function	FAD diphosphatase activity	IDA	21951714, 38688286
GO:0072388	Process	Flavin adenine dinucleotide biosynthetic process	IEA

Other IDs

• MIM: 610595
• HGNC: 24671
• e!Ensembl: ENSG00000160688

Protein

• UniProt ID: Q8NFF5
• Protein name: FAD synthase (EC 2.7.7.2) (FAD pyrophosphorylase) (FMN adenylyltransferase) (Flavin adenine dinucleotide synthase) [Includes: Molybdenum cofactor biosynthesis protein-like region; FAD synthase region]
• Protein function: Catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme.
• PDB: 8ROM, 8RON
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00994	MoCF_biosynth	114 → 276	Probable molybdopterin binding domain	Domain
  PF01507	PAPS_reduct	398 → 480	Phosphoadenosine phosphosulfate reductase family	Family
  PF01507	PAPS_reduct	463 → 555	Phosphoadenosine phosphosulfate reductase family	Family

• Sequence:

  MGWDLGTRLFQRQEQRSRLSRIWLEKTRVFLEGSTRTPALPHCLFWLLQVPSTQDPLFPG
  YGPQCPVDLAGPPCLRPLFGGLGGYWRALQRGREGRTMTSRASELSPGRSVTAGIIIVGD
  EILKGHTQDTNTFFLCRTLRSLGVQVCRVSVVPDEVATIAAEVTSFSNRFTHVLTAGGIG
  PTHDDVTFEAVAQAFGDELKPHPKLEAATKALGGEGWEKLSLVPSSARLHYGTDPCTGQP
  FRFPLVSVRNVYLFPGIPELLRRVLEGMKGLFQNPAVQFHSKELYVAADEASIAPILAEA
  QAHFGRRLGLGSYPDWGSNYYQVKLTLDSEEEGPLEECLAYLTARLPQGSLVPYMPNAVE
  QASEAVYKLAESGSSLGKKVAGALQTIETSLAQYSLTQLCVGFNGGKDCTALLHLFHAAV
  QRKLPDVPNPLQILYIRSISPFPELEQFLQDTIKRYNLQMLEAEGSMKQALGELQARHPQ
  LEAVLMGTRRTDPYSCSLCPFSPTDPGWPAFMRINPLLDWTYRDIWDFLRQLFVPYCILY
  DRGYTSLGSRENTVRNPALKCLSPGGHPTYRPAYLLENEEEERNSRT

• Sequence length: 587

Pathways

KEGG:

Riboflavin metabolism
Metabolic pathways
Biosynthesis of cofactors

Reactome:

Vitamin B2 (riboflavin) metabolism

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
FLAD1-related disorder	Likely pathogenic; Pathogenic	rs771466122	RCV003407734	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Multiple acyl-CoA dehydrogenase deficiency	Pathogenic; Likely pathogenic	rs876661314, rs876661313, rs876661315, rs876661312, rs876661310, rs876661311, rs876661309, rs771466122, rs199979286	RCV000223942 RCV000223949 RCV000223946 RCV000223945 RCV000223944 RCV000223939 RCV000223940 RCV000223948 RCV000986423	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Myopathy with abnormal lipid metabolism	Pathogenic; Likely pathogenic	rs1657723514, rs876661313, rs876661312, rs876661310, rs876661311, rs876661309, rs771466122, rs1057518160, rs199979286	RCV001542637 RCV000234837 RCV000234836 RCV000234839 RCV000234842 RCV000234840 RCV000234835 RCV001542550 RCV004689943	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Adrenocortical carcinoma, hereditary	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	-	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; -	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Asthma	Asthma	BEFREE	21933193, 26283408		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	BEFREE	31455761		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	34336008	Stimulate	★☆☆☆☆ Found in Text Mining only
Carbamoyl-Phosphate Synthase I Deficiency Disease	Carbamoyl Phosphate Synthase Deficiency	BEFREE	28433476		★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	37254652	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	18320251, 24853887, 25008580		★☆☆☆☆ Found in Text Mining only
Coronary Arteriosclerosis	Coronary Arteriosclerosis	BEFREE	18842780, 21040914, 23383292, 28237083, 29074585		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	18842780, 21040914, 23383292, 27004414, 28237083, 29074585		★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	18842780, 21040914, 23383292, 28237083, 29074585		★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	28552045		★☆☆☆☆ Found in Text Mining only
Dermatitis, Atopic	Dermatitis	BEFREE	26633493		★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	21733300		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	21733300		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	24985009, 27004414, 29032079, 29899246		★☆☆☆☆ Found in Text Mining only
Dyslipidemias	Dyslipidemias	BEFREE	29074585, 29858861		★☆☆☆☆ Found in Text Mining only
Eczema	Eczema	BEFREE	20948998, 21366865, 26633493		★☆☆☆☆ Found in Text Mining only
Familial Alzheimer Disease (FAD)	Alzheimer disease	BEFREE	27259049, 7723630, 8080245		★☆☆☆☆ Found in Text Mining only
Familial lichen amyloidosis	Lichen amyloidosis	BEFREE	27197070		★☆☆☆☆ Found in Text Mining only
Hypospadias	Hypospadias	BEFREE	30061063		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	27273350		★☆☆☆☆ Found in Text Mining only
Inborn Errors of Metabolism	Inborn Errors Of Metabolism	BEFREE	27259049		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory Bowel Disease	BEFREE	29549916		★☆☆☆☆ Found in Text Mining only
Ischemic stroke	Ischemic Stroke	BEFREE	25008580		★☆☆☆☆ Found in Text Mining only
LIPID STORAGE MYOPATHY DUE TO FLAVIN ADENINE DINUCLEOTIDE SYNTHETASE DEFICIENCY	Lipid Storage Myopathy	CLINGEN_DG	16643857, 20060505, 25058219, 27259049		★☆☆☆☆ Found in Text Mining only
LIPID STORAGE MYOPATHY DUE TO FLAVIN ADENINE DINUCLEOTIDE SYNTHETASE DEFICIENCY	Lipid Storage Myopathy	UNIPROT_DG	27259049		★☆☆☆☆ Found in Text Mining only
LIPID STORAGE MYOPATHY DUE TO FLAVIN ADENINE DINUCLEOTIDE SYNTHETASE DEFICIENCY	Lipid Storage Myopathy	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
LIPID STORAGE MYOPATHY DUE TO FLAVIN ADENINE DINUCLEOTIDE SYNTHETASE DEFICIENCY	Lipid Storage Myopathy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	BEFREE	28552045		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	27197070		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	29491470		★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	BEFREE	30680745		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	28552045		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	30982706, 31392824		★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome X	Metabolic Syndrome	BEFREE	21733300		★☆☆☆☆ Found in Text Mining only
Mild cognitive disorder	Cognitive disorder	BEFREE	27273350		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	25058219	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Respiratory Chain Deficiencies	Mitochondrial Respiratory Chain Deficiencies	BEFREE	27259049, 30061063, 31835305		★☆☆☆☆ Found in Text Mining only
Multiple Acyl Coenzyme A Dehydrogenase Deficiency	Multiple Acyl-CoA Dehydrogenase Deficiency	BEFREE	27259049, 29316637, 30061063, 30982706, 31392824		★☆☆☆☆ Found in Text Mining only
Multiple Acyl Coenzyme A Dehydrogenase Deficiency	Multiple Acyl-CoA Dehydrogenase Deficiency	CLINVAR_DG	27259049		★☆☆☆☆ Found in Text Mining only
Multiple acyl-CoA dehydrogenase deficiency, mild type	Multiple Acyl-CoA Dehydrogenase Deficiency	Orphanet			★☆☆☆☆ Found in Text Mining only
Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type	Multiple Acyl-CoA Dehydrogenase Deficiency	Orphanet			★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myopathy with Abnormal Lipid Metabolism	Myopathy With Abnormal Lipid Metabolism	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Neoplasms	Neoplasms	BEFREE	21242119		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	28598979, 29795460		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	37254652	Associate	★☆☆☆☆ Found in Text Mining only
Pena-Shokeir syndrome type I	Pena Shokeir syndrome	BEFREE	19645055		★☆☆☆☆ Found in Text Mining only
Penile hypospadias	Penile Hypospadias	BEFREE	30061063		★☆☆☆☆ Found in Text Mining only
PNEUMOTHORAX, PRIMARY SPONTANEOUS	Pneumothorax	BEFREE	19645055		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	BEFREE	26879377		★☆☆☆☆ Found in Text Mining only
Progressive supranuclear palsy	Progressive Supranuclear Palsy	BEFREE	19645055		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	27197070		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	29491470		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	32714079	Stimulate	★☆☆☆☆ Found in Text Mining only