Normal Function
The ACTG2 gene provides instructions for making a protein called gamma (γ)-2 actin, which is part of the actin protein family. Actin proteins are organized into filaments, which are important for the tensing of muscle fibers (muscle contraction) and cell movement. These filaments also help maintain the cytoskeleton, which is the structural framework that determines cell shape and organizes cell contents.
The γ-2 actin protein is found in smooth muscle cells of the urinary and intestinal tracts. Smooth muscles line the internal organs; they contract and relax without being consciously controlled. The γ-2 actin protein is necessary for contraction of the smooth muscles in the bladder and intestines. These contractions empty urine from the bladder and move food through the intestines as part of the digestive process.
Health Conditions Related to Genetic Changes
Intestinal pseudo-obstruction
Several inherited mutations in the ACTG2 gene have been identified in people with intestinal pseudo-obstruction, a condition that impairs the smooth muscle contractions that move food through the digestive tract (peristalsis). This condition mimics a physical blockage of the intestines without an actual obstruction. Problems with emptying the bladder can also occur in people with this disorder.
The ACTG2 gene mutations that cause intestinal pseudo-obstruction are thought to hinder the formation of actin filaments in the cytoskeleton and reduce the ability of smooth muscles in the intestines and bladder to contract. As a result, peristalsis in the intestines is impaired and the bladder is less able to contract and expel urine, leading to the signs and symptoms of this condition.
More About This Health ConditionMegacystis-microcolon-intestinal hypoperistalsis syndrome
At least 22 ACTG2 gene mutations have been found to cause megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), which is characterized by impairment of peristalsis and emptying the bladder.
The ACTG2 gene mutations that cause MMIHS are not inherited; rather they occur as a random (de novo) event during the formation of reproductive cells (eggs or sperm) or in early embryonic development. The alterations change single protein building blocks (amino acids) in the γ-2 actin protein. These changes hinder the formation of actin filaments and reduce the ability of smooth muscles in the bladder and intestines to contract. As a result, the bladder cannot empty normally, leading to an enlarged bladder (megacystis) and painful abdominal swelling (distention). In addition, partially digested food can build up in the intestines, which also contributes to distention. Poor digestion may lead to malnutrition in people with MMIHS.
More About This Health ConditionOther disorders
ACTG2 gene mutations cause a spectrum of disorders (sometimes referred to as ACTG2-related disorders), with MMIHS (described above) at the severe end. As in MMIHS, most of these mutations change single amino acids in the γ-2 actin protein. However, in less severely affected individuals, the mutations are usually inherited. These mutations often cause intestinal pseudo-obstruction (described above). In some affected individuals, the smooth muscle problems are episodic and come and go throughout life. Intestinal malrotation can also occur in people with ACTG2 gene mutations. This condition occurs when the intestines do not fold properly; instead, they twist abnormally, which can impede the movement of food. Effects on the urinary tract include recurrent urinary tract infections and impaired bladder function. Individuals with inherited ACTG2 gene mutations can have one or more of these intestinal or urinary tract abnormalities; they are usually milder than MMIHS, or they begin later in life. It is unclear why inherited and de novo mutations result in conditions with different severities.
Other Names for This Gene
- ACT
- ACTA3
- ACTE
- actin, gamma-enteric smooth muscle isoform 1 precursor
- actin, gamma-enteric smooth muscle isoform 2 precursor
- actin-like protein
- ACTL3
- ACTSG
- alpha-actin-3
- VSCM
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Halim D, Hofstra RM, Signorile L, Verdijk RM, van der Werf CS, Sribudiani Y, Brouwer RW, van IJcken WF, Dahl N, Verheij JB, Baumann C, Kerner J, van Bever Y, Galjart N, Wijnen RM, Tibboel D, Burns AJ, Muller F, Brooks AS, Alves MM. ACTG2 variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis Syndrome. Hum Mol Genet. 2016 Feb 1;25(3):571-83. doi: 10.1093/hmg/ddv497. Epub 2015 Dec 8. Citation on PubMed
- Lehtonen HJ, Sipponen T, Tojkander S, Karikoski R, Jarvinen H, Laing NG, Lappalainen P, Aaltonen LA, Tuupanen S. Segregation of a missense variant in enteric smooth muscle actin gamma-2 with autosomal dominant familial visceral myopathy. Gastroenterology. 2012 Dec;143(6):1482-1491.e3. doi: 10.1053/j.gastro.2012.08.045. Epub 2012 Sep 6. Citation on PubMed
- Matera I, Rusmini M, Guo Y, Lerone M, Li J, Zhang J, Di Duca M, Nozza P, Mosconi M, Pini Prato A, Martucciello G, Barabino A, Morandi F, De Giorgio R, Stanghellini V, Ravazzolo R, Devoto M, Hakonarson H, Ceccherini I. Variants of the ACTG2 gene correlate with degree of severity and presence of megacystis in chronic intestinal pseudo-obstruction. Eur J Hum Genet. 2016 Aug;24(8):1211-5. doi: 10.1038/ejhg.2015.275. Epub 2016 Jan 27. Citation on PubMed or Free article on PubMed Central
- Thorson W, Diaz-Horta O, Foster J 2nd, Spiliopoulos M, Quintero R, Farooq A, Blanton S, Tekin M. De novo ACTG2 mutations cause congenital distended bladder, microcolon, and intestinal hypoperistalsis. Hum Genet. 2014 Jun;133(6):737-42. doi: 10.1007/s00439-013-1406-0. Epub 2013 Dec 13. Citation on PubMed
- Wangler MF, Gonzaga-Jauregui C, Gambin T, Penney S, Moss T, Chopra A, Probst FJ, Xia F, Yang Y, Werlin S, Eglite I, Kornejeva L, Bacino CA, Baldridge D, Neul J, Lehman EL, Larson A, Beuten J, Muzny DM, Jhangiani S; Baylor-Hopkins Center for Mendelian Genomics; Gibbs RA, Lupski JR, Beaudet A. Heterozygous de novo and inherited mutations in the smooth muscle actin (ACTG2) gene underlie megacystis-microcolon-intestinal hypoperistalsis syndrome. PLoS Genet. 2014 Mar 27;10(3):e1004258. doi: 10.1371/journal.pgen.1004258. eCollection 2014 Mar. Citation on PubMed or Free article on PubMed Central
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