Reviewed August 2007
What is the official name of the ALS2 gene?
The official name of this gene is “amyotrophic lateral sclerosis 2 (juvenile).”
ALS2 is the gene's official symbol. The ALS2 gene is also known by other names, listed below.
What is the normal function of the ALS2 gene?
The ALS2 gene provides instructions for making a protein called alsin. Alsin is produced in a wide range of tissues, with highest amounts in the brain. It is particularly abundant in motor neurons, the specialized nerve cells in the brain and spinal cord that control the movement of muscles.
Alsin's function in cells is unclear. It may play a role in regulating cell membrane organization and the movement of molecules inside cells. Research findings also suggest that alsin may play a role in the development of axons and dendrites, which are specialized outgrowths from nerve cells that are essential for the transmission of nerve impulses.
How are changes in the ALS2 gene related to health conditions?
- amyotrophic lateral sclerosis - caused by mutations in the ALS2 gene
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Two ALS2 mutations that cause type 2 amyotrophic lateral sclerosis have been identified. These mutations delete a single DNA building block (nucleotide), which alters the instructions for producing alsin. As a result, alsin is unstable and decays rapidly.
It is unclear how the loss of alsin protein causes type 2 amyotrophic lateral sclerosis. Loss of alsin may disrupt the movement of essential molecules within cells or alter the development of axons and dendrites. Researchers suggest that the long axons of motor neurons may be particularly sensitive to altered development. As a result, motor neuron function declines and eventually these nerve cells die, leading to the signs and symptoms of type 2 amyotrophic lateral sclerosis.
- infantile-onset ascending hereditary spastic paralysis - caused by mutations in the ALS2 gene
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Researchers have identified several ALS2 mutations that cause infantile-onset ascending hereditary spastic paralysis. These mutations change or delete one or more DNA building blocks (nucleotides), which alters the instructions for producing alsin. As a result, alsin is unstable and decays rapidly.
It is unclear how the loss of alsin protein causes infantile-onset ascending hereditary spastic paralysis. Loss of alsin may disrupt the movement of essential molecules within cells or alter the development of axons and dendrites. Researchers suggest that the long axons of motor neurons may be particularly sensitive to altered development. As a result, motor neuron function declines and eventually these nerve cells die, leading to the signs and symptoms of infantile-onset ascending hereditary spastic paralysis.
- juvenile primary lateral sclerosis - caused by mutations in the ALS2 gene
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Researchers have identified three mutations in the ALS2 gene that cause juvenile primary lateral sclerosis. Two of these mutations delete DNA building blocks (nucleotides), and one mutation replaces one nucleotide with an incorrect nucleotide. These mutations alter the instructions for producing alsin. As a result, alsin is unstable and decays rapidly, or it is disabled and cannot function properly.
It is unclear how the loss of functional alsin protein causes juvenile primary lateral sclerosis. Loss of alsin may disrupt the movement of essential molecules within cells or alter the development of axons and dendrites. Researchers suggest that the long axons of motor neurons may be particularly sensitive to altered development. As a result, motor neuron function declines and eventually these nerve cells die, leading to the signs and symptoms of juvenile primary lateral sclerosis.
Where is the ALS2 gene located?
Cytogenetic Location: 2q33.2
Molecular Location on chromosome 2: base pairs 202,273,521 to 202,353,982
The ALS2 gene is located on the long (q) arm of chromosome 2 at position 33.2.
More precisely, the ALS2 gene is located from base pair 202,273,521 to base pair 202,353,982 on chromosome 2.
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 ALS2?
You and your healthcare professional may find the following resources about ALS2 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/entrez/query.fcgi?CMD=search&DB=PubMed&term=((ALS2[TIAB])+OR+(amyotrophic+lateral+sclerosis+2[TIAB]))+OR+((ALS2CR6[TIAB])+OR+(alsin[TIAB])+OR+(ALSJ[TIAB])+OR+(IAHSP[TIAB])+OR+(KIAA1563[TIAB])+OR+(PLSJ[TIAB])+OR+(ALS,+juvenile+type[TIAB]))+AND+((Genes[MH])+OR+(Genetic+Phenomena[MH]))+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=3600+Days)
- OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606352)
- Research Resources - Tools for researchers
- Entrez Gene (http://view.ncbi.nlm.nih.gov/gene/57679)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp?ALS2)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=443)
What other names do people use for the ALS2 gene or gene products?
- ALS2CR6
- ALS2_HUMAN
- ALSJ
- IAHSP
- KIAA1563
- PLSJ
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 ALS2?
axons ;
cell ;
cell membrane ;
dendrite ;
DNA ;
gene ;
juvenile ;
molecule ;
motor ;
motor neuron ;
mutation ;
nerve cell ;
neuron ;
nucleotide ;
protein ;
sclerosis ;
sign ;
symptom ;
tissue
You may find definitions for these and many other terms in the Genetics Home Reference
Glossary (http://ghr.nlm.nih.gov/glossary).
References
- Devon RS, Helm JR, Rouleau GA, Leitner Y, Lerman-Sagie T, Lev D, Hayden MR. The first nonsense mutation in alsin results in a homogeneous phenotype of infantile-onset ascending spastic paralysis with bulbar involvement in two siblings. Clin Genet. 2003 Sep;64(3):210-5. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12919135)
- Eymard-Pierre E, Lesca G, Dollet S, Santorelli FM, di Capua M, Bertini E, Boespflug-Tanguy O. Infantile-onset ascending hereditary spastic paralysis is associated with mutations in the alsin gene. Am J Hum Genet. 2002 Sep;71(3):518-27. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12145748)
- Eymard-Pierre E, Yamanaka K, Haeussler M, Kress W, Gauthier-Barichard F, Combes P, Cleveland DW, Boespflug-Tanguy O. Novel missense mutation in ALS2 gene results in infantile ascending hereditary spastic paralysis. Ann Neurol. 2006 Jun;59(6):976-80. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16718699)
- Gros-Louis F, Meijer IA, Hand CK, Dube MP, MacGregor DL, Seni MH, Devon RS, Hayden MR, Andermann F, Andermann E, Rouleau GA. An ALS2 gene mutation causes hereditary spastic paraplegia in a Pakistani kindred. Ann Neurol. 2003 Jan;53(1):144-5. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12509863)
- Hadano S, Hand CK, Osuga H, Yanagisawa Y, Otomo A, Devon RS, Miyamoto N, Showguchi-Miyata J, Okada Y, Singaraja R, Figlewicz DA, Kwiatkowski T, Hosler BA, Sagie T, Skaug J, Nasir J, Brown RH Jr, Scherer SW, Rouleau GA, Hayden MR, Ikeda JE. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat Genet. 2001 Oct;29(2):166-73. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11586298)
- Kress JA, Kuhnlein P, Winter P, Ludolph AC, Kassubek J, Muller U, Sperfeld AD. Novel mutation in the ALS2 gene in juvenile amyotrophic lateral sclerosis. Ann Neurol. 2005 Nov;58(5):800-3. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16240357)
- Kunst CB. Complex genetics of amyotrophic lateral sclerosis. Am J Hum Genet. 2004 Dec;75(6):933-47. Epub 2004 Oct 11. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15478096)
- Millecamps S, Gentil BJ, Gros-Louis F, Rouleau G, Julien JP. Alsin is partially associated with centrosome in human cells. Biochim Biophys Acta. 2005 Aug 15;1745(1):84-100. Epub 2005 Jan 19. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16085057)
- Otomo A, Hadano S, Okada T, Mizumura H, Kunita R, Nishijima H, Showguchi-Miyata J, Yanagisawa Y, Kohiki E, Suga E, Yasuda M, Osuga H, Nishimoto T, Narumiya S, Ikeda JE. ALS2, a novel guanine nucleotide exchange factor for the small GTPase Rab5, is implicated in endosomal dynamics. Hum Mol Genet. 2003 Jul 15;12(14):1671-87. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12837691)
- Panzeri C, De Palma C, Martinuzzi A, Daga A, De Polo G, Bresolin N, Miller CC, Tudor EL, Clementi E, Bassi MT. The first ALS2 missense mutation associated with JPLS reveals new aspects of alsin biological function. Brain. 2006 Jul;129(Pt 7):1710-9. Epub 2006 May 2. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16670179)
- Tudor EL, Perkinton MS, Schmidt A, Ackerley S, Brownlees J, Jacobsen NJ, Byers HL, Ward M, Hall A, Leigh PN, Shaw CE, McLoughlin DM, Miller CC. ALS2/Alsin regulates Rac-PAK signaling and neurite outgrowth. J Biol Chem. 2005 Oct 14;280(41):34735-40. Epub 2005 Jul 26. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16049005)
- Yamanaka K, Vande Velde C, Eymard-Pierre E, Bertini E, Boespflug-Tanguy O, Cleveland DW. Unstable mutants in the peripheral endosomal membrane component ALS2 cause early-onset motor neuron disease. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):16041-6. Epub 2003 Dec 10. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14668431)
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
healthcare professional.
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
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