Reviewed June 2012
What is the official name of the PITX2 gene?
The official name of this gene is “paired-like homeodomain 2.”
PITX2 is the gene's official symbol. The PITX2 gene is also known by other names, listed below.
What is the normal function of the PITX2 gene?
The PITX2 gene provides instructions for making a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this action, the PITX2 protein is called a transcription factor. The PITX2 gene is part of a family of homeobox genes, which act during early embryonic development to control the formation of many parts of the body.
The PITX2 protein plays a critical role in early development, particularly in the formation of structures in the front part of the eye (the anterior segment). These structures include the colored part of the eye (the iris), the central hole in the iris through which light enters the eye (the pupil), and the clear front covering of the eye (the cornea). Studies suggest that the PITX2 protein also has functions in the adult eye, such as helping cells respond to oxidative stress. Oxidative stress occurs when unstable molecules called free radicals accumulate to levels that can damage or kill cells.
The PITX2 protein is also involved in the normal development of other parts of the body, including the teeth, heart, and abdominal organs.
Does the PITX2 gene share characteristics with other genes?
The PITX2 gene belongs to a family of genes called homeobox (homeoboxes).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
How are changes in the PITX2 gene related to health conditions?
- Axenfeld-Rieger syndrome - caused by mutations in the PITX2 gene
More than 45 mutations in the PITX2 gene have been found to cause Axenfeld-Rieger syndrome type 1, a condition that affects the development of the anterior segment of the eye and other parts of the body. Most PITX2 gene mutations reduce the amount of functional PITX2 protein that is produced in cells. However, some genetic changes (such as a duplication of the PITX2 gene) increase the amount or function of the PITX2 protein. Having either too little or too much of this protein disrupts the regulation of other genes needed for normal development.
Eye development appears to be the most sensitive to changes in PITX2 protein activity, which is why abnormalities of the anterior segment of the eye are the predominant features of Axenfeld-Rieger syndrome. However, changes in the amount of PITX2 protein can also lead to distinctive facial features, tooth abnormalities, and problems with development of other parts of the body in people with this condition.
- other disorders - caused by mutations in the PITX2 gene
Mutations in the PITX2 gene have also been identified in rare cases of several other eye disorders. Like Axenfeld-Rieger syndrome, these conditions primarily involve the anterior segment of the eye. They include Peters anomaly, which is a developmental condition characterized by thinning and clouding of the cornea, and ring dermoid of the cornea, a condition associated with tumor-like growths on the cornea. Mutations in the PITX2 gene have also been found in a few people with iris hypoplasia or iridogoniodysgenesis type 2, conditions that cause underdevelopment of the iris. Iridogoniodysgenesis type 2 is also associated with an elevated risk of increased pressure in the eye (glaucoma).
Where is the PITX2 gene located?
Cytogenetic Location: 4q25
Molecular Location on chromosome 4: base pairs 111,538,578 to 111,563,278
The PITX2 gene is located on the long (q) arm of chromosome 4 at position 25.
More precisely, the PITX2 gene is located from base pair 111,538,578 to base pair 111,563,278 on chromosome 4.
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 PITX2?
You and your healthcare professional may find the following resources about PITX2 helpful.
Educational resources - Information pages
- Transcriptional Control of Neural Crest Development (2010): Pitx2 (http://www.ncbi.nlm.nih.gov/books/NBK53140/)
- University of Arizona: Cornea, Ring Dermoid (http://disorders.eyes.arizona.edu/handouts/cornea-ring-dermoid)
- University of Arizona: Iridogoniodysgenesis (http://disorders.eyes.arizona.edu/category/keywords/iridogoniodysgenesis)
- University of Arizona: Peters Anomaly (http://disorders.eyes.arizona.edu/handouts/peters-anomaly)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for PITX2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=5308%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=(PITX2%5BTIAB%5D)%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- IRIDOGONIODYSGENESIS, TYPE 2 (http://omim.org/entry/137600)
- PAIRED-LIKE HOMEODOMAIN TRANSCRIPTION FACTOR 2 (http://omim.org/entry/601542)
- PETERS ANOMALY (http://omim.org/entry/604229)
- RING DERMOID OF CORNEA (http://omim.org/entry/180550)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_PITX2.html)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/5308)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=5308)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=9005)
What other names do people use for the PITX2 gene or gene products?
- all1-responsive gene 1
- paired-like homeodomain transcription factor 2
- pituitary homeobox 2
- rieg bicoid-related homeobox transcription factor 1
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 PITX2?
free radicals ;
oxidative stress ;
transcription factor ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Berry FB, Lines MA, Oas JM, Footz T, Underhill DA, Gage PJ, Walter MA. Functional interactions between FOXC1 and PITX2 underlie the sensitivity to FOXC1 gene dose in Axenfeld-Rieger syndrome and anterior segment dysgenesis. Hum Mol Genet. 2006 Mar 15;15(6):905-19. Epub 2006 Jan 31. (http://www.ncbi.nlm.nih.gov/pubmed/16449236?dopt=Abstract)
- D'haene B, Meire F, Claerhout I, Kroes HY, Plomp A, Arens YH, de Ravel T, Casteels I, De Jaegere S, Hooghe S, Wuyts W, van den Ende J, Roulez F, Veenstra-Knol HE, Oldenburg RA, Giltay J, Verheij JB, de Faber JT, Menten B, De Paepe A, Kestelyn P, Leroy BP, De Baere E. Expanding the spectrum of FOXC1 and PITX2 mutations and copy number changes in patients with anterior segment malformations. Invest Ophthalmol Vis Sci. 2011 Jan 21;52(1):324-33. doi: 10.1167/iovs.10-5309. (http://www.ncbi.nlm.nih.gov/pubmed/20881294?dopt=Abstract)
- Doward W, Perveen R, Lloyd IC, Ridgway AE, Wilson L, Black GC. A mutation in the RIEG1 gene associated with Peters' anomaly. J Med Genet. 1999 Feb;36(2):152-5. (http://www.ncbi.nlm.nih.gov/pubmed/10051017?dopt=Abstract)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/5308)
- Footz T, Idrees F, Acharya M, Kozlowski K, Walter MA. Analysis of mutations of the PITX2 transcription factor found in patients with Axenfeld-Rieger syndrome. Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2599-606. doi: 10.1167/iovs.08-3251. Epub 2009 Feb 14. (http://www.ncbi.nlm.nih.gov/pubmed/19218601?dopt=Abstract)
- Pearce WG, Mielke BC, Kulak SC, Walter MA. Histopathology and molecular basis of iridogoniodysgenesis syndrome. Ophthalmic Genet. 1999 Jun;20(2):83-8. (http://www.ncbi.nlm.nih.gov/pubmed/10420192?dopt=Abstract)
- Strungaru MH, Dinu I, Walter MA. Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations. Invest Ophthalmol Vis Sci. 2007 Jan;48(1):228-37. (http://www.ncbi.nlm.nih.gov/pubmed/17197537?dopt=Abstract)
- Strungaru MH, Footz T, Liu Y, Berry FB, Belleau P, Semina EV, Raymond V, Walter MA. PITX2 is involved in stress response in cultured human trabecular meshwork cells through regulation of SLC13A3. Invest Ophthalmol Vis Sci. 2011 Sep 29;52(10):7625-33. doi: 10.1167/iovs.10-6967. (http://www.ncbi.nlm.nih.gov/pubmed/21873665?dopt=Abstract)
- Tümer Z, Bach-Holm D. Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. Eur J Hum Genet. 2009 Dec;17(12):1527-39. doi: 10.1038/ejhg.2009.93. Epub 2009 Jun 10. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19513095?dopt=Abstract)
- Xia K, Wu L, Liu X, Xi X, Liang D, Zheng D, Cai F, Pan Q, Long Z, Dai H, Hu Z, Tang B, Zhang Z, Xia J. Mutation in PITX2 is associated with ring dermoid of the cornea. J Med Genet. 2004 Dec;41(12):e129. (http://www.ncbi.nlm.nih.gov/pubmed/15591271?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.