Reviewed January 2015
What is the official name of the ACTA2 gene?
The official name of this gene is “actin, alpha 2, smooth muscle, aorta.”
ACTA2 is the gene's official symbol. The ACTA2 gene is also known by other names, listed below.
What is the normal function of the ACTA2 gene?
The ACTA2 gene provides instructions for making a protein called smooth muscle alpha (α)-2 actin, which is part of the actin protein family. Actin proteins are important for cell movement and the tensing (contraction) of muscles.
Smooth muscle α-2 actin is found in smooth muscle cells. Smooth muscles line the internal organs, including the blood vessels, stomach, and intestines. Within smooth muscle cells, smooth muscle α-2 actin forms the core of structures called sarcomeres, which are necessary for muscles to contract. Smooth muscles contract and relax as part of their normal function without being consciously controlled.
Layers of smooth muscle cells are found in the walls of the arteries, which are blood vessels that carry blood from the heart to the rest of the body. Smooth muscle α-2 actin contributes to the ability of these muscles to contract, which allows the arteries to maintain their shape instead of stretching out as blood is pumped through them.
How are changes in the ACTA2 gene related to health conditions?
- familial thoracic aortic aneurysm and dissection - caused by mutations in the ACTA2 gene
More than 30 ACTA2 gene mutations have been identified in people with familial thoracic aortic aneurysm and dissection (familial TAAD). This disorder involves problems with the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. The aorta can weaken and stretch, causing a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection). Aortic aneurysm and dissection can cause life-threatening internal bleeding.
ACTA2 gene mutations that are associated with familial TAAD change single protein building blocks (amino acids) in the smooth muscle α-2 actin protein. These changes likely affect the way the protein functions in smooth muscle contraction, interfering with the sarcomeres' ability to prevent arteries from stretching. The aorta, where the force of pumping blood coming directly from the heart is most intense, is particularly vulnerable to this stretching, resulting in the aortic aneurysms and dissections associated with familial TAAD.
- other disorders - caused by mutations in the ACTA2 gene
At least one mutation in the ACTA2 gene causes multisystemic smooth muscle dysfunction syndrome. This disorder impairs the activity of smooth muscles throughout the body and leads to widespread problems including blood vessel abnormalities, decreased response of the pupils to light, a weak (hypotonic) bladder, and impairment of the muscle contractions that move food through the digestive tract (hypoperistalsis).
The mutation that causes multisystemic smooth muscle dysfunction syndrome replaces the amino acid arginine with the amino acid histidine at protein position 179, written as Arg179His or R179H. This mutation results in impaired contraction of smooth muscles in many organs, leading to the signs and symptoms of multisystemic smooth muscle dysfunction syndrome. It is unclear why this ACTA2 gene mutation has effects on smooth muscles throughout the body while others affect only the aorta.
Where is the ACTA2 gene located?
Cytogenetic Location: 10q23.3
Molecular Location on chromosome 10: base pairs 88,935,074 to 88,991,390
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/59))
The ACTA2 gene is located on the long (q) arm of chromosome 10 at position 23.3.
More precisely, the ACTA2 gene is located from base pair 88,935,074 to base pair 88,991,390 on chromosome 10.
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 ACTA2?
You and your healthcare professional may find the following resources about ACTA2 helpful.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1120)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for ACTA2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=59%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=%28ACTA2%5BTIAB%5D%29%20OR%20%28AAT6%5BTIAB%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- ACTIN, ALPHA-2, SMOOTH MUSCLE, AORTA (http://omim.org/entry/102620)
- MULTISYSTEMIC SMOOTH MUSCLE DYSFUNCTION SYNDROME (http://omim.org/entry/613834)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_ACTA2.html)
- HGNC Gene Family: Actins (http://www.genenames.org/cgi-bin/genefamilies/set/929)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=130)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/59)
What other names do people use for the ACTA2 gene or gene products?
- actin, aortic smooth muscle
- alpha 2 actin
- cell growth-inhibiting gene 46 protein
- growth-inhibiting gene 46
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 ACTA2?
amino acid ;
aortic dissection ;
muscle cells ;
You may find definitions for these and many other terms in the Genetics Home Reference
- OMIM: ACTIN, ALPHA-2, SMOOTH MUSCLE, AORTA (http://omim.org/entry/102620)
- El-Hamamsy I, Yacoub MH. Cellular and molecular mechanisms of thoracic aortic aneurysms. Nat Rev Cardiol. 2009 Dec;6(12):771-86. doi: 10.1038/nrcardio.2009.191. Epub 2009 Nov 3. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19884902?dopt=Abstract)
- Gene Review: Thoracic Aortic Aneurysms and Aortic Dissections (http://www.ncbi.nlm.nih.gov/books/NBK1120)
- Grond-Ginsbach C, Pjontek R, Aksay SS, Hyhlik-Dürr A, Böckler D, Gross-Weissmann ML. Spontaneous arterial dissection: phenotype and molecular pathogenesis. Cell Mol Life Sci. 2010 Jun;67(11):1799-815. doi: 10.1007/s00018-010-0276-z. Epub 2010 Feb 14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20155481?dopt=Abstract)
- Guo DC, Pannu H, Tran-Fadulu V, Papke CL, Yu RK, Avidan N, Bourgeois S, Estrera AL, Safi HJ, Sparks E, Amor D, Ades L, McConnell V, Willoughby CE, Abuelo D, Willing M, Lewis RA, Kim DH, Scherer S, Tung PP, Ahn C, Buja LM, Raman CS, Shete SS, Milewicz DM. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007 Dec;39(12):1488-93. Epub 2007 Nov 11. Erratum in: Nat Genet. 2008 Feb;40(2):255. (http://www.ncbi.nlm.nih.gov/pubmed/17994018?dopt=Abstract)
- Jondeau G, Boileau C. Genetics of thoracic aortic aneurysms. Curr Atheroscler Rep. 2012 Jun;14(3):219-26. doi: 10.1007/s11883-012-0241-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22415348?dopt=Abstract)
- Milewicz DM, Carlson AA, Regalado ES. Genetic testing in aortic aneurysm disease: PRO. Cardiol Clin. 2010 May;28(2):191-7. doi: 10.1016/j.ccl.2010.01.017. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20452526?dopt=Abstract)
- Milewicz DM, Guo DC, Tran-Fadulu V, Lafont AL, Papke CL, Inamoto S, Kwartler CS, Pannu H. Genetic basis of thoracic aortic aneurysms and dissections: focus on smooth muscle cell contractile dysfunction. Annu Rev Genomics Hum Genet. 2008;9:283-302. doi: 10.1146/annurev.genom.8.080706.092303. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18544034?dopt=Abstract)
- Milewicz DM, Østergaard JR, Ala-Kokko LM, Khan N, Grange DK, Mendoza-Londono R, Bradley TJ, Olney AH, Adès L, Maher JF, Guo D, Buja LM, Kim D, Hyland JC, Regalado ES. De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction. Am J Med Genet A. 2010 Oct;152A(10):2437-43. doi: 10.1002/ajmg.a.33657. (http://www.ncbi.nlm.nih.gov/pubmed/20734336?dopt=Abstract)
- Morisaki H, Akutsu K, Ogino H, Kondo N, Yamanaka I, Tsutsumi Y, Yoshimuta T, Okajima T, Matsuda H, Minatoya K, Sasaki H, Tanaka H, Ishibashi-Ueda H, Morisaki T. Mutation of ACTA2 gene as an important cause of familial and nonfamilial nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD). Hum Mutat. 2009 Oct;30(10):1406-11. doi: 10.1002/humu.21081. (http://www.ncbi.nlm.nih.gov/pubmed/19639654?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/59)
- Pyeritz RE. Heritable thoracic aortic disorders. Curr Opin Cardiol. 2014 Jan;29(1):97-102. doi: 10.1097/HCO.0000000000000023. Review. (http://www.ncbi.nlm.nih.gov/pubmed/24284977?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.