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PRODH gene

proline dehydrogenase 1

Normal Function

The PRODH gene provides instructions for producing the enzyme proline dehydrogenase (also known as proline oxidase), which is found primarily in the brain, lung, and muscle. Within cells of these organs, this enzyme functions in energy-producing structures called mitochondria.

Proline dehydrogenase plays a role in the process of breaking down the protein building block (amino acid) proline. Specifically, the enzyme starts the reaction that converts proline to pyrroline-5-carboxylate. A subsequent step converts this intermediate product 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


More than 20 variants (also known as mutations) in the PRODH gene have been found to cause hyperprolinemia type I.  Hyperprolinemia is an excess of proline in the blood. Type I is generally characterized by a lack of symptoms, although some severely affected individual have neurological problems such as seizures or intellectual disability. PRODH gene variants change single amino acids in the enzyme and reduce the activity of the proline dehydrogenase enzyme, causing a decrease in its ability to break down proline. A decrease in proline breakdown results in a buildup of proline in the body, and leads to hyperprolinemia.

More About This Health Condition

Other disorders

Several studies have shown an association between variations in the PRODH gene and psychiatric disorders such as schizophrenia, while others have shown no significant association. Most of the variations in the PRODH gene result in the substitution of one amino acid for another in the proline dehydrogenase enzyme. The amino acid substitution reduces the enzyme's activity, resulting in decreased breakdown of proline and a buildup of proline in the body. Researchers believe that hyperprolinemia (described above) may affect the action of certain chemicals that transmit signals between nerve cells (neurons) in the brain (neurotransmitters), resulting in an increased risk of psychiatric disorders.

Other Names for This Gene

  • FLJ33744
  • HSPOX2
  • MGC148078
  • MGC148079
  • p53 induced protein
  • PIG6
  • PRODH1
  • PRODH2
  • proline dehydrogenase (oxidase) 1
  • proline dehydrogenase (proline oxidase )
  • proline oxidase 2
  • Proline oxidase, mitochondrial
  • SCZD4
  • TP53I6
  • tumor protein p53 inducible protein 6

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases


  • Bender HU, Almashanu S, Steel G, Hu CA, Lin WW, Willis A, Pulver A, Valle D. Functional consequences of PRODH missense mutations. Am J Hum Genet. 2005 Mar;76(3):409-20. doi: 10.1086/428142. Epub 2005 Jan 20. Citation on PubMed or Free article on PubMed Central
  • Campbell HD, Webb GC, Young IG. A human homologue of the Drosophila melanogaster sluggish-A (proline oxidase) gene maps to 22q11.2, and is a candidate gene for type-I hyperprolinaemia. Hum Genet. 1997 Nov;101(1):69-74. doi: 10.1007/s004390050589. Citation on PubMed
  • Goodman BK, Rutberg J, Lin WW, Pulver AE, Thomas GH. Hyperprolinaemia in patients with deletion (22)(q11.2) syndrome. J Inherit Metab Dis. 2000 Dec;23(8):847-8. doi: 10.1023/a:1026773005303. No abstract available. Citation on PubMed
  • Hoogendoorn B, Coleman SL, Guy CA, Smith SK, O'Donovan MC, Buckland PR. Functional analysis of polymorphisms in the promoter regions of genes on 22q11. Hum Mutat. 2004 Jul;24(1):35-42. doi: 10.1002/humu.20061. Citation on PubMed
  • Jacquet H, Berthelot J, Bonnemains C, Simard G, Saugier-Veber P, Raux G, Campion D, Bonneau D, Frebourg T. The severe form of type I hyperprolinaemia results from homozygous inactivation of the PRODH gene. J Med Genet. 2003 Jan;40(1):e7. doi: 10.1136/jmg.40.1.e7. No abstract available. Citation on PubMed or Free article on PubMed Central
  • Jacquet H, Demily C, Houy E, Hecketsweiler B, Bou J, Raux G, Lerond J, Allio G, Haouzir S, Tillaux A, Bellegou C, Fouldrin G, Delamillieure P, Menard JF, Dollfus S, D'Amato T, Petit M, Thibaut F, Frebourg T, Campion D. Hyperprolinemia is a risk factor for schizoaffective disorder. Mol Psychiatry. 2005 May;10(5):479-85. doi: 10.1038/ Citation on PubMed
  • Jacquet H, Rapoport JL, Hecketsweiler B, Bobb A, Thibaut F, Frebourg T, Campion D. Hyperprolinemia is not associated with childhood onset schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2006 Mar 5;141B(2):192. doi: 10.1002/ajmg.b.30263. Citation on PubMed
  • Jacquet H, Raux G, Thibaut F, Hecketsweiler B, Houy E, Demilly C, Haouzir S, Allio G, Fouldrin G, Drouin V, Bou J, Petit M, Campion D, Frebourg T. PRODH mutations and hyperprolinemia in a subset of schizophrenic patients. Hum Mol Genet. 2002 Sep 15;11(19):2243-9. doi: 10.1093/hmg/11.19.2243. Citation on PubMed
  • Li D, He L. Association study of the G-protein signaling 4 (RGS4) and proline dehydrogenase (PRODH) genes with schizophrenia: a meta-analysis. Eur J Hum Genet. 2006 Oct;14(10):1130-5. doi: 10.1038/sj.ejhg.5201680. Epub 2006 Jun 21. Citation on PubMed
  • Li T, Ma X, Sham PC, Sun X, Hu X, Wang Q, Meng H, Deng W, Liu X, Murray RM, Collier DA. Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population. Am J Med Genet B Neuropsychiatr Genet. 2004 Aug 15;129B(1):13-5. doi: 10.1002/ajmg.b.30049. Citation on PubMed
  • Raux G, Bumsel E, Hecketsweiler B, van Amelsvoort T, Zinkstok J, Manouvrier-Hanu S, Fantini C, Breviere GM, Di Rosa G, Pustorino G, Vogels A, Swillen A, Legallic S, Bou J, Opolczynski G, Drouin-Garraud V, Lemarchand M, Philip N, Gerard-Desplanches A, Carlier M, Philippe A, Nolen MC, Heron D, Sarda P, Lacombe D, Coizet C, Alembik Y, Layet V, Afenjar A, Hannequin D, Demily C, Petit M, Thibaut F, Frebourg T, Campion D. Involvement of hyperprolinemia in cognitive and psychiatric features of the 22q11 deletion syndrome. Hum Mol Genet. 2007 Jan 1;16(1):83-91. doi: 10.1093/hmg/ddl443. Epub 2006 Nov 29. 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. Citation on PubMed
  • Williams HJ, Williams N, Spurlock G, Norton N, Zammit S, Kirov G, Owen MJ, O'Donovan MC. Detailed analysis of PRODH and PsPRODH reveals no association with schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2003 Jul 1;120B(1):42-6. doi: 10.1002/ajmg.b.20049. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.