Table 2 Genes variants associated with late-onset riboflavin-responsive phenotypes
From: New insights into the nutritional genomics of adult-onset riboflavin-responsive diseases
Gene name/Id | Protein | Gene Ontogeny Classification/tissue gene expression | Physiological functions | Clinical Features associated with genetic variants responding to riboflavin supplementation | Variants involved in late onset and riboflavin responsive symptoms | OMIM Phenotype | Riboflavin supplementation | References |
|---|---|---|---|---|---|---|---|---|
Riboflavin transporters | ||||||||
SLC52A1/55065 | hRFT1 | Membrane transporter/ Placenta and intestine | Riboflavin membrane transport | Transient neonatal riboflavin deficiency/maternal deficiency Transient MADD Phenotype | rs346822, rs2304445, rs141935493 | 615,026 | 50 or 100 mg/day | |
SLC52A2/79581 | hRFT3 | Membrane transporter/ brain and most other tissues | Riboflavin membrane transport | Riboflavin deficency Brown-Vialetto-Van Laere Syndrome (BVVLS) | rs117500243, rs397514538, rs377740960, | 614,707 | 50 mg/kg/day in paediatric patients and 1500 mg/day in adult patients | |
SLC52A3/113278 | hRFT2 | Membrane transporter/ testis/ intestine | Riboflavin membrane transport | Riboflavin deficency Brown-Vialetto-Van Laere Syndrome (BVVLS) Fazio-Londe syndrome Late onset | rs267606, rs140360713, rs1439187603, rs1431398048 | 211,530 | 10–25 mg⁄kg⁄day or 200 mg/day | |
SLC25A32/81034 | MFTC | Ubiquitous | FAD and folate mitochondrial transport | Recurrent exercise intolerance | rs147014855 rs142329098 rs1249586962 | 616,839 | 10-30mg/day | [31] |
FAD synthesis | ||||||||
FLAD1/80308 | FAD synthase | Converting FMN into FAD/ Ubiquitous expression | FAD biosynthesis | lipid storage myopathy and multiple-respiratory-chain deficiency elevation of multiple acylcarnitines, increased urinary organic acids | rs876661310, rs876661311, rs771466122, rs876661309 | 255,100 | 100mg/day | [36] |
Flavin dependent enzymes | ||||||||
ETFDH/2110 ETFA/2108 ETFB/2109 | Electron transfer flavoprotein-ubiquinone oxidoreductase | Accepts electrons from ETF and reduces ubiquinone | Transport of electrons mitochondrial respiratory chain | MADD (type III) Exercise intolerance, myalgia, chronic fatigue, metabolic acidosis | rs121964954, rs887871605, rs762928354, rs887871, rs121964955, rs369912835, rs147219158, rs760234838, rs780768015 | 231,680 | 100 -300mg/day | |
MTHFR/4524 | Methylenetetrahydrofolate reductase | Reductase in one-carbon-metabolism/ ubiquitous | Converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate | Associated with increased incident hypertension and increased circulating homocysteine | rs1801133 | 236,250 | 16 mg/day | |
ACAD9/28976 | Acyl-CoA dehydrogenase 9 | Mitochondrial/ubiquitously expressed | Assembly of the mitochondrial CI, Fatty Acid Beta-Oxidation | Growth retardation, Exercise intolerance | rs762521317 rs1057518752 rs779610933, rs863224844, rs149753643, rs777282696, rs1553732136 | 611,126 | 40mg/day | |