Normal Function
The ATRX gene provides instructions for making a protein that plays an essential role in normal development. Although the specific function of the ATRX protein is unknown, studies suggest that it helps regulate the activity (expression) of other genes through a process known as chromatin remodeling. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed.
The ATRX protein appears to regulate the expression of two genes, HBA1 and HBA2, that are necessary for the production of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen to cells throughout the body. Other genes regulated by the ATRX protein have not been identified.
Health Conditions Related to Genetic Changes
Alpha thalassemia X-linked intellectual disability syndrome
More than 125 mutations in the ATRX gene have been identified in people with alpha thalassemia X-linked intellectual disability syndrome. The most common mutations change single protein building blocks (amino acids) in the ATRX protein. Other mutations insert or delete genetic material in the ATRX gene or alter how the gene's instructions are used to make the protein.
Mutations may destabilize the ATRX protein or affect its interactions with other proteins. These changes prevent the ATRX protein from effectively regulating gene expression. Reduced activity of the HBA1 and HBA2 genes causes a blood disorder called alpha thalassemia. Abnormal expression of additional genes likely causes developmental delay, distinctive facial features, and the other signs and symptoms of alpha thalassemia X-linked intellectual disability syndrome.
More About This Health ConditionOther disorders
Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are not inherited, are called somatic mutations. Somatic mutations of the ATRX gene have been found in some people with blood and bone marrow disorders. In particular, researchers have found somatic ATRX gene mutations in some cases of myelodysplastic syndrome (MDS), which is a bone marrow disorder that usually occurs in older males.
Somatic ATRX gene mutations do not cause MDS; instead, they occur as the condition progresses. Like inherited mutations in the ATRX gene, somatic mutations reduce the activity of the HBA1 and HBA2 genes and cause alpha thalassemia. When alpha thalassemia occurs in people with MDS, the combination of disorders is often referred to as alpha thalassemia myelodysplastic syndrome (ATMDS).
Other Names for This Gene
- alpha thalassemia/mental retardation syndrome X-linked
- alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae)
- ATR2
- ATRX_HUMAN
- DNA dependent ATPase and helicase
- helicase 2, X-linked
- MGC2094
- MRXHF1
- RAD54
- RAD54L
- SFM1
- SHS
- transcriptional regulator ATRX
- X-linked nuclear protein
- XH2
- XNP
- Zinc finger helicase
- ZNF-HX
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Argentaro A, Yang JC, Chapman L, Kowalczyk MS, Gibbons RJ, Higgs DR, Neuhaus D, Rhodes D. Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX. Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11939-44. doi: 10.1073/pnas.0704057104. Epub 2007 Jul 3. Citation on PubMed or Free article on PubMed Central
- Badens C, Lacoste C, Philip N, Martini N, Courrier S, Giuliano F, Verloes A, Munnich A, Leheup B, Burglen L, Odent S, Van Esch H, Levy N. Mutations in PHD-like domain of the ATRX gene correlate with severe psychomotor impairment and severe urogenital abnormalities in patients with ATRX syndrome. Clin Genet. 2006 Jul;70(1):57-62. doi: 10.1111/j.1399-0004.2006.00641.x. Citation on PubMed
- Gibbons R. Alpha thalassaemia-mental retardation, X linked. Orphanet J Rare Dis. 2006 May 4;1:15. doi: 10.1186/1750-1172-1-15. Citation on PubMed or Free article on PubMed Central
- Gibbons RJ, Pellagatti A, Garrick D, Wood WG, Malik N, Ayyub H, Langford C, Boultwood J, Wainscoat JS, Higgs DR. Identification of acquired somatic mutations in the gene encoding chromatin-remodeling factor ATRX in the alpha-thalassemia myelodysplasia syndrome (ATMDS). Nat Genet. 2003 Aug;34(4):446-9. doi: 10.1038/ng1213. Citation on PubMed
- Gibbons RJ, Wada T, Fisher CA, Malik N, Mitson MJ, Steensma DP, Fryer A, Goudie DR, Krantz ID, Traeger-Synodinos J. Mutations in the chromatin-associated protein ATRX. Hum Mutat. 2008 Jun;29(6):796-802. doi: 10.1002/humu.20734. Citation on PubMed
- Steensma DP, Gibbons RJ, Higgs DR. Acquired alpha-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies. Blood. 2005 Jan 15;105(2):443-52. doi: 10.1182/blood-2004-07-2792. Epub 2004 Sep 9. Citation on PubMed
- Steensma DP, Higgs DR, Fisher CA, Gibbons RJ. Acquired somatic ATRX mutations in myelodysplastic syndrome associated with alpha thalassemia (ATMDS) convey a more severe hematologic phenotype than germline ATRX mutations. Blood. 2004 Mar 15;103(6):2019-26. doi: 10.1182/blood-2003-09-3360. Epub 2003 Oct 30. Citation on PubMed
- Xue Y, Gibbons R, Yan Z, Yang D, McDowell TL, Sechi S, Qin J, Zhou S, Higgs D, Wang W. The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies. Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10635-40. doi: 10.1073/pnas.1937626100. Epub 2003 Sep 2. Citation on PubMed or Free article on PubMed Central
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