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ALDH4A1 gene

aldehyde dehydrogenase 4 family member A1
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Normal Function

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 between proline and glutamate is important in maintaining a supply of the amino acids needed for protein production, and for energy transfer within the cell.

Health Conditions Related to Genetic Changes

Hyperprolinemia

Researchers have identified three mutations in the ALDH4A1 gene that eliminate the function of the pyrroline-5-carboxylate dehydrogenase enzyme, causing hyperprolinemia type II. Two of these mutations add or delete a DNA building block (nucleotide), which introduces a premature stop signal that results in an abnormally shortened enzyme. The third mutation results in the substitution of the amino acid leucine for the amino acid serine at position 352 (written as Ser352Leu or S352L) in the pyrroline-5-carboxylate dehydrogenase enzyme. Nonfunctional pyrroline-5-carboxylate dehydrogenase leads to elevated levels of proline and a buildup of the 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

  • AL4H1_HUMAN
  • aldehyde dehydrogenase 4 family, member A1
  • aldehyde dehydrogenase 4A1
  • ALDH4
  • mitochondrial delta-1-pyrroline 5-carboxylate dehydrogenase
  • P5C dehydrogenase
  • P5CD
  • P5CDh
  • P5CDhL
  • P5CDhS

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • 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
  • 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
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