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Normal Function
The AAAS gene provides instructions for making a protein called ALADIN whose function is not well understood. Within cells, ALADIN is found in the nuclear envelope, the structure that surrounds the nucleus and separates it from the rest of the cell. Based on its location, ALADIN is thought to be involved in the movement of molecules into and out of the nucleus.
Health Conditions Related to Genetic Changes
Triple A syndrome
At least 49 mutations in the AAAS gene have been found to cause triple A syndrome. These mutations change the structure of ALADIN in different ways; however, almost all mutations prevent this protein from reaching its proper location in the nuclear envelope. The absence of ALADIN likely disrupts the movement of molecules across this membrane. Researchers suspect that DNA repair proteins may be unable to enter the nucleus if ALADIN is missing from the nuclear envelope. DNA damage that is not repaired can cause the cell to become unstable and lead to cell death. Although the nervous system is particularly vulnerable to DNA damage, it remains unknown exactly how mutations in the AAAS gene lead to the signs and symptoms of triple A syndrome.
More About This Health ConditionOther Names for This Gene
- AAA
- AAAS_HUMAN
- AAASb
- achalasia, adrenocortical insufficiency, alacrimia
- achalasia, adrenocortical insufficiency, alacrimia (Allgrove, triple-A)
- ADRACALA
- ADRACALIN
- ALADIN
- DKFZp586G1624
- GL003
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Brooks BP, Kleta R, Stuart C, Tuchman M, Jeong A, Stergiopoulos SG, Bei T, Bjornson B, Russell L, Chanoine JP, Tsagarakis S, Kalsner L, Stratakis C. Genotypic heterogeneity and clinical phenotype in triple A syndrome: a review of the NIH experience 2000-2005. Clin Genet. 2005 Sep;68(3):215-21. doi: 10.1111/j.1399-0004.2005.00482.x. Citation on PubMed
- Handschug K, Sperling S, Yoon SJ, Hennig S, Clark AJ, Huebner A. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Hum Mol Genet. 2001 Feb 1;10(3):283-90. doi: 10.1093/hmg/10.3.283. Citation on PubMed
- Kind B, Koehler K, Lorenz M, Huebner A. The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope. Biochem Biophys Res Commun. 2009 Dec 11;390(2):205-10. doi: 10.1016/j.bbrc.2009.09.080. Epub 2009 Sep 24. Citation on PubMed
- Kiriyama T, Hirano M, Asai H, Ikeda M, Furiya Y, Ueno S. Restoration of nuclear-import failure caused by triple A syndrome and oxidative stress. Biochem Biophys Res Commun. 2008 Oct 3;374(4):631-4. doi: 10.1016/j.bbrc.2008.07.088. Epub 2008 Jul 26. Citation on PubMed
- Prpic I, Huebner A, Persic M, Handschug K, Pavletic M. Triple A syndrome: genotype-phenotype assessment. Clin Genet. 2003 May;63(5):415-7. doi: 10.1034/j.1399-0004.2003.00070.x. Citation on PubMed
- Storr HL, Kind B, Parfitt DA, Chapple JP, Lorenz M, Koehler K, Huebner A, Clark AJ. Deficiency of ferritin heavy-chain nuclear import in triple a syndrome implies nuclear oxidative damage as the primary disease mechanism. Mol Endocrinol. 2009 Dec;23(12):2086-94. doi: 10.1210/me.2009-0056. Epub 2009 Oct 23. Citation on PubMed
- Tullio-Pelet A, Salomon R, Hadj-Rabia S, Mugnier C, de Laet MH, Chaouachi B, Bakiri F, Brottier P, Cattolico L, Penet C, Begeot M, Naville D, Nicolino M, Chaussain JL, Weissenbach J, Munnich A, Lyonnet S. Mutant WD-repeat protein in triple-A syndrome. Nat Genet. 2000 Nov;26(3):332-5. doi: 10.1038/81642. Citation on PubMed
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