Reviewed February 2010
What is the official name of the AAAS gene?
The official name of this gene is “achalasia, adrenocortical insufficiency, alacrimia.”
AAAS is the gene's official symbol. The AAAS gene is also known by other names, listed below.
What is the normal function of the AAAS gene?
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.
Does the AAAS gene share characteristics with other genes?
The AAAS gene belongs to a family of genes called WDR (WD repeat domain containing).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
How are changes in the AAAS gene related to health conditions?
- triple A syndrome - caused by mutations in the AAAS gene
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.
Where is the AAAS gene located?
Cytogenetic Location: 12q13
Molecular Location on chromosome 12: base pairs 53,307,456 to 53,321,628
The AAAS gene is located on the long (q) arm of chromosome 12 at position 13.
More precisely, the AAAS gene is located from base pair 53,307,456 to base pair 53,321,628 on chromosome 12.
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 AAAS?
You and your healthcare professional may find the following resources about AAAS helpful.
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=%28AAAS%5BTIAB%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20NOT%20%28%28aneurysm%29%20OR%20%28American%20Association%20for%20the%20Advancement%20of%20Science%29%20OR%20%28Time%20traveling%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201440%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/605378)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_AAAS.html)
- HGNC Gene Family: Nucleoporins (http://www.genenames.org/cgi-bin/genefamilies/set/1051)
- HGNC Gene Family: WD repeat domain containing (http://www.genenames.org/cgi-bin/genefamilies/set/362)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=13666)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/8086)
What other names do people use for the AAAS gene or gene products?
- achalasia, adrenocortical insufficiency, alacrimia (Allgrove, triple-A)
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 AAAS?
DNA damage ;
DNA repair ;
nervous system ;
nuclear envelope ;
You may find definitions for these and many other terms in the Genetics Home Reference
- OMIM: AAAS GENE (http://omim.org/entry/605378)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/16098009?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/11159947?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/19782045?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/18662670?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/8086)
- Prpic I, Huebner A, Persic M, Handschug K, Pavletic M. Triple A syndrome: genotype-phenotype assessment. Clin Genet. 2003 May;63(5):415-7. (http://www.ncbi.nlm.nih.gov/pubmed/12752575?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/19855093?dopt=Abstract)
- Tullio-Pelet A, Salomon R, Hadj-Rabia S, Mugnier C, de Laet MH, Chaouachi B, Bakiri F, Brottier P, Cattolico L, Penet C, Bégeot 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. (http://www.ncbi.nlm.nih.gov/pubmed/11062474?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.