Reviewed May 2012
What is the official name of the TH gene?
The official name of this gene is “tyrosine hydroxylase.”
TH is the gene's official symbol. The TH gene is also known by other names, listed below.
What is the normal function of the TH gene?
The TH gene provides instructions for making the enzyme tyrosine hydroxylase, which is important for normal functioning of the nervous system. Tyrosine hydroxylase takes part in the first step of the pathway that produces a group of hormones called catecholamines. This enzyme helps convert the protein building block (amino acid) tyrosine to a catecholamine called dopamine. Dopamine is also known as a neurotransmitter because it transmits signals between nerve cells in the brain to help control physical movement and emotional behavior. Other catecholamines called norepinephrine and epinephrine are produced from dopamine. Norepinephrine and epinephrine are involved in the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature.
How are changes in the TH gene related to health conditions?
- dopa-responsive dystonia - caused by mutations in the TH gene
More than two dozen mutations in the TH gene have been found to cause dopa-responsive dystonia. This condition is characterized by a pattern of involuntary muscle contractions (dystonia), tremors, and other uncontrolled movements and usually responds to treatment with a medication called L-Dopa. Most TH gene mutations that cause this condition change single protein building blocks (amino acids) in the tyrosine hydroxylase enzyme, resulting in a decrease in functional enzyme. A reduction in normal tyrosine hydroxylase enzyme leads to a decrease in the production of dopamine, which causes the movement problems characteristic of dopa-responsive dystonia. The amount of functional enzyme that is produced is associated with the severity of the signs and symptoms. Less functional enzyme leads to more severe symptoms.
- tyrosine hydroxylase deficiency - caused by mutations in the TH gene
More than 20 mutations in the TH gene have been identified in people with tyrosine hydroxylase (TH) deficiency. These mutations result in reduced activity of the tyrosine hydroxylase enzyme. As a result, the body produces less dopamine, norepinephrine, and epinephrine. These catecholamines are necessary for normal nervous system function, and changes in their levels contribute to the abnormal movements, nervous system dysfunction, and other neurological problems seen in people with TH deficiency.
Dopa-responsive dystonia is sometimes considered a mild form of tyrosine hydroxylase deficiency. It is uncertain whether they are two separate disorders or part of the same disease spectrum.
- other disorders - associated with the TH gene
Certain common TH variations (polymorphisms) modify catecholamine production, which affects the risk of developing conditions associated with regulation of the autonomic nervous system. These TH gene polymorphisms affect the extent to which blood pressure increases with stress and may increase the risk of high blood pressure (hypertension).
One TH gene polymorphism has been associated with sudden infant death syndrome (SIDS). SIDS is a major cause of death in babies younger than 1 year. It is characterized by sudden and unexplained death, usually during sleep. The polymorphism, called allele *9.3, is the most common TH gene polymorphism among people of European descent and has been identified in a larger percentage of babies who die from SIDS than in other babies. This version of the gene may affect the regulation of breathing or awakening in infants.
Where is the TH gene located?
Cytogenetic Location: 11p15.5
Molecular Location on chromosome 11: base pairs 2,163,928 to 2,171,804
The TH gene is located on the short (p) arm of chromosome 11 at position 15.5.
More precisely, the TH gene is located from base pair 2,163,928 to base pair 2,171,804 on chromosome 11.
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 TH?
You and your healthcare professional may find the following resources about TH helpful.
Educational resources - Information pages
- Basic Neurochemistry (6th edition, 1999): Tyrosine hydroxylase is the rate-limiting enzyme for the biosynthesis of catecholamines (http://www.ncbi.nlm.nih.gov/books/NBK27988/)
- Neuroscience (second edition, 2001): Regulation of tyrosine hydroxylase by protein phosphorylation (image) (http://www.ncbi.nlm.nih.gov/books/NBK10990/figure/A576/)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1437)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for TH (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=7054%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- OMIM - Genetic disorder catalog (http://omim.org/entry/191290)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_TH.html)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=7054)
- HGNC Gene Symbol Report (http://www.genenames.org/data/hgnc_data.php?hgnc_id=11782)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7054)
What other names do people use for the TH gene or gene products?
- tyrosine 3-monooxygenase
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 TH?
amino acid ;
autonomic nervous system ;
nervous system ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Furukawa Y, Kish SJ, Fahn S. Dopa-responsive dystonia due to mild tyrosine hydroxylase deficiency. Ann Neurol. 2004 Jan;55(1):147-8. (http://www.ncbi.nlm.nih.gov/pubmed/14705130?dopt=Abstract)
- Gene Review: Tyrosine Hydroxylase Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK1437)
- Hoffmann GF, Assmann B, Bräutigam C, Dionisi-Vici C, Häussler M, de Klerk JB, Naumann M, Steenbergen-Spanjers GC, Strassburg HM, Wevers RA. Tyrosine hydroxylase deficiency causes progressive encephalopathy and dopa-nonresponsive dystonia. Ann Neurol. 2003;54 Suppl 6:S56-65. (http://www.ncbi.nlm.nih.gov/pubmed/12891655?dopt=Abstract)
- Hunt SC. Tyrosine hydroxylase: another piece of the genetics of hypertension puzzle. Circulation. 2007 Aug 28;116(9):970-2. (http://www.ncbi.nlm.nih.gov/pubmed/17724269?dopt=Abstract)
- Klintschar M, Reichenpfader B, Saternus KS. A functional polymorphism in the tyrosine hydroxylase gene indicates a role of noradrenalinergic signaling in sudden infant death syndrome. J Pediatr. 2008 Aug;153(2):190-3. doi: 10.1016/j.jpeds.2008.02.032. Epub 2008 Apr 3. (http://www.ncbi.nlm.nih.gov/pubmed/18534229?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7054)
- Pearl PL, Capp PK, Novotny EJ, Gibson KM. Inherited disorders of neurotransmitters in children and adults. Clin Biochem. 2005 Dec;38(12):1051-8. Epub 2005 Nov 18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16298354?dopt=Abstract)
- Pearl PL, Taylor JL, Trzcinski S, Sokohl A. The pediatric neurotransmitter disorders. J Child Neurol. 2007 May;22(5):606-16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17690069?dopt=Abstract)
- Rao F, Zhang L, Wessel J, Zhang K, Wen G, Kennedy BP, Rana BK, Das M, Rodriguez-Flores JL, Smith DW, Cadman PE, Salem RM, Mahata SK, Schork NJ, Taupenot L, Ziegler MG, O'Connor DT. Adrenergic polymorphism and the human stress response. Ann N Y Acad Sci. 2008 Dec;1148:282-96. doi: 10.1196/annals.1410.085. (http://www.ncbi.nlm.nih.gov/pubmed/19120120?dopt=Abstract)
- Rao F, Zhang L, Wessel J, Zhang K, Wen G, Kennedy BP, Rana BK, Das M, Rodriguez-Flores JL, Smith DW, Cadman PE, Salem RM, Mahata SK, Schork NJ, Taupenot L, Ziegler MG, O'Connor DT. Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis: discovery of common human genetic variants governing transcription, autonomic activity, and blood pressure in vivo. Circulation. 2007 Aug 28;116(9):993-1006. Epub 2007 Aug 13. (http://www.ncbi.nlm.nih.gov/pubmed/17698732?dopt=Abstract)
- Schiller A, Wevers RA, Steenbergen GC, Blau N, Jung HH. Long-term course of L-dopa-responsive dystonia caused by tyrosine hydroxylase deficiency. Neurology. 2004 Oct 26;63(8):1524-6. (http://www.ncbi.nlm.nih.gov/pubmed/15505183?dopt=Abstract)
- OMIM: TYROSINE HYDROXYLASE (http://omim.org/entry/191290)
- Verbeek MM, Steenbergen-Spanjers GC, Willemsen MA, Hol FA, Smeitink J, Seeger J, Grattan-Smith P, Ryan MM, Hoffmann GF, Donati MA, Blau N, Wevers RA. Mutations in the cyclic adenosine monophosphate response element of the tyrosine hydroxylase gene. Ann Neurol. 2007 Oct;62(4):422-6. (http://www.ncbi.nlm.nih.gov/pubmed/17696123?dopt=Abstract)
- Yeung WL, Wong VC, Chan KY, Hui J, Fung CW, Yau E, Ko CH, Lam CW, Mak CM, Siu S, Low L. Expanding phenotype and clinical analysis of tyrosine hydroxylase deficiency. J Child Neurol. 2011 Feb;26(2):179-87. doi: 10.1177/0883073810377014. Epub 2010 Sep 7. Erratum in: J Child Neurol. 2012 Jun;27(6):829-31. (http://www.ncbi.nlm.nih.gov/pubmed/20823027?dopt=Abstract)
- Zhang L, Rao F, Wessel J, Kennedy BP, Rana BK, Taupenot L, Lillie EO, Cockburn M, Schork NJ, Ziegler MG, O'Connor DT. Functional allelic heterogeneity and pleiotropy of a repeat polymorphism in tyrosine hydroxylase: prediction of catecholamines and response to stress in twins. Physiol Genomics. 2004 Nov 17;19(3):277-91. Epub 2004 Sep 14. (http://www.ncbi.nlm.nih.gov/pubmed/15367723?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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.