The ALDH4A1 gene provides instructions for producing the enzyme pyrroline-5-carboxylate dehydrogenase, which is found in tissues throughout the body. Within the cells of these tissues, this enzyme functions in energy-producing structures called mitochondria.
Pyrroline-5-carboxylate dehydrogenase starts the second step in the process that breaks down the protein building block (amino acid) proline. This step converts pyrroline-5-carboxylate, which is produced in the first step, to the amino acid glutamate.
The conversion of proline to glutamate (and the conversion of glutamate to proline, which is controlled by different enzymes) is important for maintaining a supply of amino acids needed for protein production, and for energy transfer within the cell.
Health Conditions Related to Genetic Changes
At least seven variants (also known as mutations) in the ALDH4A1 gene have been found to cause hyperprolinemia type II. Hyperprolinemia is an excess of proline in the blood. Type II is generally the most severe form of the disorder and is characterized by neurological problems such as seizures or intellectual disability.
ALDH4A1 gene variants reduce or eliminate the function of the pyrroline-5-carboxylate dehydrogenase enzyme. A lack of pyrroline-5-carboxylate dehydrogenase function leads to decreased breakdown of proline and elevated levels of proline and intermediate breakdown product pyrroline-5-carboxylate, causing the signs and symptoms of hyperprolinemia type II.More About This Health Condition
Other Names for This Gene
- aldehyde dehydrogenase 4 family, member A1
- aldehyde dehydrogenase 4A1
- mitochondrial delta-1-pyrroline 5-carboxylate dehydrogenase
- P5C dehydrogenase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Geraghty MT, Vaughn D, Nicholson AJ, Lin WW, Jimenez-Sanchez G, Obie C, Flynn MP, Valle D, Hu CA. Mutations in the Delta1-pyrroline 5-carboxylate dehydrogenase gene cause type II hyperprolinemia. Hum Mol Genet. 1998 Sep;7(9):1411-5. Citation on PubMed
- Hu CA, Lin WW, Valle D. Cloning, characterization, and expression of cDNAs encoding human delta 1-pyrroline-5-carboxylate dehydrogenase. J Biol Chem. 1996 Apr 19;271(16):9795-800. Citation on PubMed
- Inagaki E, Ohshima N, Takahashi H, Kuroishi C, Yokoyama S, Tahirov TH. Crystal structure of Thermus thermophilus Delta1-pyrroline-5-carboxylate dehydrogenase. J Mol Biol. 2006 Sep 22;362(3):490-501. Epub 2006 Jul 29. Citation on PubMed
- Sophos NA, Vasiliou V. Aldehyde dehydrogenase gene superfamily: the 2002 update. Chem Biol Interact. 2003 Feb 1;143-144:5-22. Citation on PubMed
- Tanner JJ. Structural Biology of Proline Catabolic Enzymes. Antioxid Redox Signal. 2019 Feb 1;30(4):650-673. doi: 10.1089/ars.2017.7374. Epub 2017 Nov 13. Review. Citation on PubMed
- Vasiliou V, Bairoch A, Tipton KF, Nebert DW. Eukaryotic aldehyde dehydrogenase (ALDH) genes: human polymorphisms, and recommended nomenclature based on divergent evolution and chromosomal mapping. Pharmacogenetics. 1999 Aug;9(4):421-34. Review. Citation on PubMed
- Vasiliou V, Pappa A. Polymorphisms of human aldehyde dehydrogenases. Consequences for drug metabolism and disease. Pharmacology. 2000 Sep;61(3):192-8. Review. Citation on PubMed
- Yoshida A, Rzhetsky A, Hsu LC, Chang C. Human aldehyde dehydrogenase gene family. Eur J Biochem. 1998 Feb 1;251(3):549-57. Review. Citation on PubMed