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ASPM Gene Abnormal Spindle Microtubule Assembly ASPM gene abnormal spindle microtubule assembly Normal Function The ASPM gene provides instructions for making a protein that is involved in cell division. This protein is found in cells and tissues throughout the body; however, it appears to be particularly important for the division of cells in the developing brain. Studies suggest that the ASPM protein helps maintain the orderly division of early brain cells called neural progenitor cells, which ultimately give rise to mature nerve cells ( neurons). By promoting the division of neural progenitor cells during early brain development, the ASPM protein helps determine the total number of neurons and the overall size of the brain. Health Conditions Related to Genetic Changes Autosomal recessive primary microcephaly Mutations in the ASPM gene are the most common cause of autosomal recessive primary microcephaly (often shortened to MCPH, which stands for "microcephaly primary hereditary"). This condition is characterized by an abnormally small head and brain, intellectual disability, and delayed development. More than 80 mutations in the ASPM gene have been found to cause MCPH. Almost all of the ASPM gene mutations responsible for MCPH reduce production of the ASPM protein. The protein that is produced is shorter than normal and is thought to be partly or wholly nonfunctional. A shortage of functional ASPM protein impairs cell division, especially in neural progenitor cells in the developing brain. As a result, fewer mature neurons are produced, and affected individuals are born with an unusually small brain. Small head size, intellectual disability, and delayed development are all consequences of the small brain size. Because the ASPM protein is found in cells throughout the body, it is unclear why ASPM gene mutations affect neural progenitor cells more severely than other cell types. Some researchers believe that neural progenitor cells are more sensitive than other types of cells to a shortage of the ASPM protein. Other researchers have suggested that another protein may be able to compensate for the loss of the ASPM protein in cells outside the brain. Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 1 Age-related macular degeneration MedlinePlus Genetics provides information about Age-related macular degeneration Cancers The ASPM gene is upregulated in several types of cancer, which means that it produces more of the ASPM protein than usual in cancer cells. In particular, upregulation of the ASPM gene has been studied in brain tumors called gliomas and liver tumors called hepatocellular carcinomas. It is unclear why the ASPM gene is abnormally active in these cancers or what effects the extra ASPM protein may have in cancer cells. However, studies suggest that unusually high activity of the ASPM gene is related to cancer progression, spread to other parts of the body (metastasis), and recurrence. Other Names for This Gene • abnormal spindle-like microcephaly-associated protein • ASP • asp (abnormal spindle) homolog, microcephaly associated (Drosophila) • ASPM_HUMAN • Calmbp1 • FLJ10517 • FLJ10549 • FLJ43117 • MCPH5 Additional Information & Resources Tests Listed in the Genetic Testing Registry • Tests of ASPM (https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=259266[geneid]) Scientific Articles on PubMed • PubMed (https://pubmed.ncbi.nlm.nih.gov/?term=%28ASPM%5BTIAB%5D%29+A ND+%28%28Genes%5BMH%5D%29+OR+%28Genetic+Phenomena%5BMH%5D %29%29+AND+english%5Bla%5D+AND+human%5Bmh%5D+AND+%22last+3600 +days%22%5Bdp%5D) Catalog of Genes and Diseases from OMIM • ABNORMAL SPINDLE-LIKE, MICROCEPHALY-ASSOCIATED (https://omim.org/e Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 2 ntry/605481) Research Resources • ClinVar (https://www.ncbi.nlm.nih.gov/clinvar?term=ASPM[gene]) • NCBI Gene (https://www.ncbi.nlm.nih.gov/gene/259266) References • Bond J, Roberts E, Mochida GH, Hampshire DJ, Scott S, Askham JM, Springell K, Mahadevan M, Crow YJ, Markham AF, Walsh CA, Woods CG. ASPM is a major determinantof cerebral cortical size. Nat Genet. 2002 Oct;32(2):316-20. Epub 2002 Sep 23. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/12355089) • Bond J, Scott S, Hampshire DJ, Springell K, Corry P, Abramowicz MJ, MochidaGH, Hennekam RC, Maher ER, Fryns JP, Alswaid A, Jafri H, Rashid Y, Mubaidin A, Walsh CA, Roberts E, Woods CG. Protein-truncating mutations in ASPM causevariable reduction in brain size. Am J Hum Genet. 2003 Nov;73(5):1170-7. Epub2003 Oct 21. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/14574646) or Free article on PubMed Central (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1 180496/) • Fish JL, Kosodo Y, Enard W, Pääbo S, Huttner WB. Aspm specifically maintainssymmetric proliferative divisions of neuroepithelial cells. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10438-10443. doi: 10.1073/pnas.0604066103. Epub 2006 Jun 23. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/16798874) or Free article on PubMed Central (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1502476/) • Hagemann C, Anacker J, Gerngras S, Kühnel S, Said HM, Patel R, Kämmerer U, Vordermark D, Roosen K, Vince GH. Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormalspindle-like, microcephaly associated) in human malignant gliomas. Oncol Rep.2008 Aug;20(2):301-8. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/18 636190) • Higgins J, Midgley C, Bergh AM, Bell SM, Askham JM, Roberts E, Binns RK,Sharif SM, Bennett C, Glover DM, Woods CG, Morrison EE, Bond J. Human ASPMparticipates in spindle organisation, spindle orientation and cytokinesis. BMCCell Biol. 2010 Nov 2;11:85. doi: 10.1186/1471-2121-11-85. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/21044324) or Free article on PubMed Central (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988714/) • Horvath S, Zhang B, Carlson M, Lu KV, Zhu S, Felciano RM, Laurance MF, Zhao W, Qi S, Chen Z, Lee Y, Scheck AC, Liau LM, Wu H, Geschwind DH, Febbo PG, KornblumHI, Cloughesy TF, Nelson SF, Mischel PS. Analysis of oncogenic signaling networksin glioblastoma identifies ASPM as a molecular target. Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17402-7. Epub 2006 Nov 7. Citation on PubMed (https:/ /pubmed.ncbi.nlm.nih.gov/17090670) or Free article on PubMed Central (https://ww Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 3 w.ncbi.nlm.nih.gov/pmc/articles/PMC1635024/) • Kouprina N, Pavlicek A, Collins NK, Nakano M, Noskov VN, Ohzeki J, Mochida GH, Risinger JI, Goldsmith P, Gunsior M, Solomon G, Gersch W, Kim JH, Barrett JC, Walsh CA, Jurka J, Masumoto H, Larionov V. The microcephaly ASPM gene isexpressed in proliferating tissues and encodes for a mitotic spindle protein. HumMol Genet. 2005 Aug 1;14(15):2155-65. Epub 2005 Jun 22. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/15972725) • Lin SY, Pan HW, Liu SH, Jeng YM, Hu FC, Peng SY, Lai PL, Hsu HC. ASPM is anovel marker for vascular invasion, early recurrence, and poor prognosis ofhepatocellular carcinoma. Clin Cancer Res. 2008 Aug 1;14(15):4814-20. doi:10. 1158/1078-0432.CCR-07-5262. Citation on PubMed (https://pubmed.ncbi.nlm.nih.go v/18676753) • Nicholas AK, Swanson EA, Cox JJ, Karbani G, Malik S, Springell K, Hampshire D, Ahmed M, Bond J, Di Benedetto D, Fichera M, Romano C, Dobyns WB, Woods CG. Themolecular landscape of ASPM mutations in primary microcephaly. J Med Genet. 2009 Apr;46(4):249-53. doi: 10.1136/jmg.2008.062380. Epub 2008 Nov 21. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/19028728) or Free article on PubMed Central (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658750/) • Verloes A, Drunat S, Passemard S. ASPM Primary Microcephaly. 2020 Apr 2. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington,Seattle; 1993-2021. Available from http://www.ncbi.nlm.nih.gov/books/NBK555474/ Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/32239881) Genomic Location The ASPM gene is found on chromosome 1 (https://medlineplus.gov/genetics/chromoso me/1/). Page last updated on 18 August 2020 Page last reviewed: 1 April 2011 Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 4.
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