Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

PAH

Reviewed January 2008

What is the official name of the PAH gene?

The official name of this gene is “phenylalanine hydroxylase.”

PAH is the gene's official symbol. The PAH gene is also known by other names, listed below.

What is the normal function of the PAH gene?

The PAH gene provides instructions for making an enzyme called phenylalanine hydroxylase. This enzyme is responsible for the first step in processing phenylalanine, which is a building block of proteins (an amino acid) obtained through the diet. Phenylalanine is found in all proteins and in some artificial sweeteners.

Phenylalanine hydroxylase is responsible for the conversion of phenylalanine to another amino acid, tyrosine. The enzyme works with a molecule called tetrahydrobiopterin (BH4) to carry out this chemical reaction. Tyrosine is used to make several types of hormones, certain chemicals that transmit signals in the brain (neurotransmitters), and a pigment called melanin, which gives hair and skin their color. Tyrosine can also be broken down into smaller molecules that are used to produce energy.

How are changes in the PAH gene related to health conditions?

phenylketonuria - caused by mutations in the PAH gene

More than 500 mutations in the PAH gene have been identified in people with phenylketonuria (PKU). Most of these mutations change single amino acids in phenylalanine hydroxylase. For example, the most common mutation in many populations replaces the amino acid arginine with the amino acid tryptophan at position 408 (written as Arg408Trp or R408W). Other PAH mutations delete small amounts of DNA from the gene or disrupt the way the gene's instructions are used to make phenylalanine hydroxylase.

PAH mutations reduce the activity of phenylalanine hydroxylase, preventing it from processing phenylalanine effectively. As a result, this amino acid can build up to toxic levels in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage.

Classic PKU, the most severe form of the disorder, occurs when phenylalanine hydroxylase activity is severely reduced or absent. People with untreated classic PKU have levels of phenylalanine high enough to cause severe brain damage and other serious medical problems. Mutations in the PAH gene that allow the enzyme to retain some activity result in milder versions of this condition, such as variant PKU or non-PKU hyperphenylalaninemia.

Where is the PAH gene located?

Cytogenetic Location: 12q22-q24.2

Molecular Location on chromosome 12: base pairs 103,232,103 to 103,311,380

The PAH gene is located on the long (q) arm of chromosome 12 between positions 22 and 24.2.

The PAH gene is located on the long (q) arm of chromosome 12 between positions 22 and 24.2.

More precisely, the PAH gene is located from base pair 103,232,103 to base pair 103,311,380 on chromosome 12.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about PAH?

You and your healthcare professional may find the following resources about PAH helpful.

  • Educational resources - Information pages
    Basic Neurochemistry (sixth edition, 1999): Phenylalanine Metabolism: Phenylketonuria (http://www.ncbi.nlm.nih.gov/books/NBK28101/)
  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1504/)

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for PAH (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=5053%5Bgeneid%5D)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((PAH%5BTI%5D)%20OR%20(phenylalanine%20hydroxylase%5BMAJR%5D)%20OR%20(phenylalanine%20hydroxylase%5BTI%5D))%20OR%20((phenylalanine%204-hydroxylase%5BTIAB%5D)%20OR%20(phenylalanine%204-monooxygenase%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/612349)

  • Research Resources - Tools for researchers

    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/5053)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=5053)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=8582)
    • PAHdb Phenylalanine Hydroxylase Locus Knowledgebase (http://www.pahdb.mcgill.ca/)

What other names do people use for the PAH gene or gene products?

  • L-Phenylalanine,tetrahydrobiopterin:oxygen oxidoreductase (4-hydroxylating)
  • PH4H_HUMAN
  • Phenylalaninase
  • Phenylalanine 4-Hydroxylase
  • Phenylalanine 4-Monooxygenase
  • PKU1

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding PAH?

acids ; amino acid ; cofactor ; DNA ; enzyme ; gene ; L-phenylalanine ; melanin ; molecule ; mutation ; neurotransmitters ; oxidoreductase ; oxygen ; phenylalanine ; pigment ; toxic ; tyrosine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Blau N, Erlandsen H. The metabolic and molecular bases of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. Mol Genet Metab. 2004 Jun;82(2):101-11. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15171997?dopt=Abstract)
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/5053)
  • Erlandsen H, Patch MG, Gamez A, Straub M, Stevens RC. Structural studies on phenylalanine hydroxylase and implications toward understanding and treating phenylketonuria. Pediatrics. 2003 Dec;112(6 Pt 2):1557-65. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14654665?dopt=Abstract)
  • Gene Review: Phenylalanine Hydroxylase Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK1504/)
  • Güttler F, Azen C, Guldberg P, Romstad A, Hanley WB, Levy HL, Matalon R, Rouse BM, Trefz F, de la Cruz F, Koch R. Impact of the phenylalanine hydroxylase gene on maternal phenylketonuria outcome. Pediatrics. 2003 Dec;112(6 Pt 2):1530-3. (http://www.ncbi.nlm.nih.gov/pubmed/14654659?dopt=Abstract)
  • Pey AL, Desviat LR, Gámez A, Ugarte M, Pérez B. Phenylketonuria: genotype-phenotype correlations based on expression analysis of structural and functional mutations in PAH. Hum Mutat. 2003 Apr;21(4):370-8. (http://www.ncbi.nlm.nih.gov/pubmed/12655546?dopt=Abstract)
  • Scriver CR. The PAH gene, phenylketonuria, and a paradigm shift. Hum Mutat. 2007 Sep;28(9):831-45. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17443661?dopt=Abstract)
  • Waters PJ. How PAH gene mutations cause hyper-phenylalaninemia and why mechanism matters: insights from in vitro expression. Hum Mutat. 2003 Apr;21(4):357-69. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12655545?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2008
Published: May 20, 2013