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URL of this page: https://medlineplus.gov/genetics/gene/atrx/

ATRX gene

ATRX chromatin remodeler

Normal Function

The ATRX gene provides instructions for making a protein that plays an essential role in normal development. The ATRX protein helps control the activity (expression) of other genes, repair DNA damage, and maintain the ends of chromosomes (telomeres). 

The ATRX protein helps regulate the expression of genes and maintains the stability of chromosomes through a process known as chromatin remodeling. Chromatin is made up of DNA and the proteins that package 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.

Two of the genes that the ATRX protein appears to regulate are HBA1 and HBA2. These genes are necessary to produce hemoglobin, which is the protein in red blood cells that carries oxygen to cells throughout the body.

Health Conditions Related to Genetic Changes

Alpha thalassemia X-linked intellectual disability syndrome

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the ATRX gene have been identified in people with alpha thalassemia X-linked intellectual disability syndrome. This condition affects intellectual functioning, red blood cells, and other body systems. 

The most common pathogenic variants that cause alpha thalassemia X-linked intellectual disability syndrome lead to the substitution of one protein building block (amino acid) for another in the ATRX protein. Other pathogenic variants insert or delete genetic material in the ATRX gene or alter how the gene's instructions are used to make the protein.

Pathogenic variants disrupt the normal function of the ATRX protein. As a result, the protein cannot effectively regulate gene expression. Reduced activity of the HBA1 and HBA2 genes causes a blood disorder called alpha thalassemia. Abnormal activity of other genes likely causes intellectual disabilities, distinctive facial features, and the other signs and symptoms of alpha thalassemia X-linked intellectual disability syndrome.

More About This Health Condition

Other disorders

Some gene variants are not inherited but are acquired during a person's lifetime and are present only in certain cells. These changes are called somatic variants. Somatic pathogenic variants in the ATRX gene are one of the genetic variants that occur most frequently in brain tumors called gliomas and in tumors of the bones or soft tissues called sarcomas. These somatic variants occur throughout the gene and often lead to the substitution of one amino acid for another. The altered proteins that likely cannot regulate gene activity, maintain the stability of chromosomes, or perform their other critical functions. Somatic ATRX gene variants are also common in people with other forms of cancer.

In rare cases, somatic variants in the ATRX gene have been found in people with blood and bone marrow disorders. In particular, somatic ATRX gene variants have been found in some cases of myelodysplastic syndrome (MDS), in which immature blood cells fail to develop normally. Somatic ATRX gene variants do not cause MDS; instead, the variants can occur as the condition progresses. The somatic ATRX gene variants cause alpha thalassemia by reducing the activity of the HBA1 and HBA2 genes. When alpha thalassemia occurs in people with MDS, the combination of disorders is often referred to as acquired alpha thalassemia myelodysplastic syndrome (ATMDS).

Other Names for This Gene

  • ATR2
  • transcriptional regulator ATRX

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

References

  • Aguilera P, Lopez-Contreras AJ. ATRX, a guardian of chromatin. Trends Genet. 2023 Jun;39(6):505-519. doi: 10.1016/j.tig.2023.02.009. Epub 2023 Mar 7. Citation on PubMed
  • 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
  • Galbraith K, Snuderl M. Molecular Pathology of Gliomas. Clin Lab Med. 2024 Jun;44(2):149-159. doi: 10.1016/j.cll.2023.08.009. 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, 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
  • Herbaux C, Duployez N, Badens C, Poret N, Gardin C, Decamp M, Eclache V, Daliphard S, Murati A, Cony-Makhoul P, Cheze S, Beve B, Lacoste C, Prebet T, Hunault-Berger M, Maloisel F, Renneville A, Figeac M, Stamatoullas-Bastard A, Bastard C, Fenaux P, Preudhomme C, Rose C; GFM (Groupe Francophone des Myelodysplasies). Incidence of ATRX mutations in myelodysplastic syndromes, the value of microcytosis. Am J Hematol. 2015 Aug;90(8):737-8. doi: 10.1002/ajh.24073. Citation on PubMed
  • Leon NY, Harley VR. ATR-X syndrome: genetics, clinical spectrum, and management. Hum Genet. 2021 Dec;140(12):1625-1634. doi: 10.1007/s00439-021-02361-5. Epub 2021 Sep 15. Citation on PubMed
  • Shen Y, Gupta K, Tan-Wong SM, Wen S, Fisher CA, Tamon L, Proudfoot NJ, Gibbons RJ, Higgs DR. ATRX loss couples genome instability at a G-rich repeat to dysregulation of human alpha-globin expression. Nat Commun. 2026 Feb 14;17(1):2749. doi: 10.1038/s41467-026-69169-7. 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
  • Stevenson RE. Alpha-Thalassemia X-Linked Intellectual Disability Syndrome. 2000 Jun 19 [updated 2020 May 28]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1449/ Citation on PubMed

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