ACSF3 gene
acyl-CoA synthetase family member 3
The ACSF3 gene provides instructions for making an enzyme involved in the formation (synthesis) of fatty acids, which are building blocks used to make fats (lipids). The ACSF3 enzyme performs a chemical reaction that converts malonic acid to malonyl-CoA, which is the first step of fatty acid synthesis. Based on this activity, the enzyme is classified as a malonyl-CoA synthetase. The ACSF3 enzyme also converts methylmalonic acid to methylmalonyl-CoA, making it a methylmalonyl-CoA synthetase as well.
Fatty acid synthesis occurs through two pathways, one of which takes place in cellular structures called mitochondria. Mitochondria convert the energy from food into a form that cells can use, and fatty acid synthesis in these structures is thought to be important for their proper functioning. The ACSF3 enzyme is found only in mitochondria and is involved in mitochondrial fatty acid synthesis.
Related Information
About a dozen mutations in the ACSF3 gene have been found in people with combined malonic and methylmalonic aciduria (CMAMMA), a condition characterized by elevated levels of chemicals known as malonic acid and methylmalonic acid in the body. This condition can cause development and growth problems beginning in childhood or neurological problems beginning in adulthood.
Most ACSF3 gene mutations involved in CMAMMA change single protein building blocks (amino acids) in the ACSF3 enzyme. The altered enzyme likely has little or no function. Because the enzyme cannot convert malonic and methylmalonic acids, they build up in the body. Damage to organs and tissues caused by accumulation of malonic and methylmalonic acids may be responsible for the signs and symptoms of CMAMMA, although the mechanisms are unclear.
Related Information
Cytogenetic Location: 16q24.3, which is the long (q) arm of chromosome 16 at position 24.3
Molecular Location: base pairs 89,093,847 to 89,160,556 on chromosome 16 (Homo sapiens Updated Annotation Release 109.20200228, GRCh38.p13) (NCBI)
Related Information
- ACSF3_HUMAN
- acyl-CoA synthetase family member 3, mitochondrial
- acyl-CoA synthetase family member 3, mitochondrial precursor
Related Information
- OMIM: ACYL-CoA SYNTHETASE FAMILY, MEMBER 3
- Alfares A, Nunez LD, Al-Thihli K, Mitchell J, Melançon S, Anastasio N, Ha KC, Majewski J, Rosenblatt DS, Braverman N. Combined malonic and methylmalonic aciduria: exome sequencing reveals mutations in the ACSF3 gene in patients with a non-classic phenotype. J Med Genet. 2011 Sep;48(9):602-5. doi: 10.1136/jmedgenet-2011-100230. Epub 2011 Jul 23.
- Sloan JL, Johnston JJ, Manoli I, Chandler RJ, Krause C, Carrillo-Carrasco N, Chandrasekaran SD, Sysol JR, O'Brien K, Hauser NS, Sapp JC, Dorward HM, Huizing M; NIH Intramural Sequencing Center Group, Barshop BA, Berry SA, James PM, Champaigne NL, de Lonlay P, Valayannopoulos V, Geschwind MD, Gavrilov DK, Nyhan WL, Biesecker LG, Venditti CP. Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria. Nat Genet. 2011 Aug 14;43(9):883-6. doi: 10.1038/ng.908.
- Watkins PA, Maiguel D, Jia Z, Pevsner J. Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome. J Lipid Res. 2007 Dec;48(12):2736-50. Epub 2007 Aug 30.
- Witkowski A, Thweatt J, Smith S. Mammalian ACSF3 protein is a malonyl-CoA synthetase that supplies the chain extender units for mitochondrial fatty acid synthesis. J Biol Chem. 2011 Sep 30;286(39):33729-36. doi: 10.1074/jbc.M111.291591. Epub 2011 Aug 16.