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Genetics Home Reference: your guide to understanding genetic conditions
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ASPM

Reviewed April 2011

What is the official name of the ASPM gene?

The official name of this gene is “asp (abnormal spindle) homolog, microcephaly associated (Drosophila).”

ASPM is the gene's official symbol. The ASPM gene is also known by other names, listed below.

What is the normal function of the ASPM gene?

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.

How are changes in the ASPM gene related to health conditions?

autosomal recessive primary microcephaly - caused by mutations in the ASPM gene

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.

cancers - associated with the ASPM gene

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.

Where is the ASPM gene located?

Cytogenetic Location: 1q31

Molecular Location on chromosome 1: base pairs 197,084,126 to 197,146,693

The ASPM gene is located on the long (q) arm of chromosome 1 at position 31.

The ASPM gene is located on the long (q) arm of chromosome 1 at position 31.

More precisely, the ASPM gene is located from base pair 197,084,126 to base pair 197,146,693 on chromosome 1.

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 ASPM?

You and your healthcare professional may find the following resources about ASPM helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the ASPM gene or gene products?

  • abnormal spindle-like microcephaly-associated protein
  • ASP
  • ASPM_HUMAN
  • Calmbp1
  • FLJ10517
  • FLJ10549
  • FLJ43117
  • MCPH5

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 ASPM?

Asp ; autosomal ; autosomal recessive ; cancer ; cell ; cell division ; disability ; gene ; hereditary ; metastasis ; microcephaly ; progenitor cells ; progression ; protein ; recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

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 determinant of cerebral cortical size. Nat Genet. 2002 Oct;32(2):316-20. Epub 2002 Sep 23. (http://www.ncbi.nlm.nih.gov/pubmed/12355089?dopt=Abstract)
  • Bond J, Scott S, Hampshire DJ, Springell K, Corry P, Abramowicz MJ, Mochida GH, 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 cause variable reduction in brain size. Am J Hum Genet. 2003 Nov;73(5):1170-7. Epub 2003 Oct 21. (http://www.ncbi.nlm.nih.gov/pubmed/14574646?dopt=Abstract)
  • Fish JL, Kosodo Y, Enard W, Pääbo S, Huttner WB. Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10438-43. Epub 2006 Jun 23. (http://www.ncbi.nlm.nih.gov/pubmed/16798874?dopt=Abstract)
  • 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, abnormal spindle-like, microcephaly associated) in human malignant gliomas. Oncol Rep. 2008 Aug;20(2):301-8. (http://www.ncbi.nlm.nih.gov/pubmed/18636190?dopt=Abstract)
  • 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 ASPM participates in spindle organisation, spindle orientation and cytokinesis. BMC Cell Biol. 2010 Nov 2;11:85. doi: 10.1186/1471-2121-11-85. (http://www.ncbi.nlm.nih.gov/pubmed/21044324?dopt=Abstract)
  • 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, Kornblum HI, Cloughesy TF, Nelson SF, Mischel PS. Analysis of oncogenic signaling networks in 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. (http://www.ncbi.nlm.nih.gov/pubmed/17090670?dopt=Abstract)
  • 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 is expressed in proliferating tissues and encodes for a mitotic spindle protein. Hum Mol Genet. 2005 Aug 1;14(15):2155-65. Epub 2005 Jun 22. (http://www.ncbi.nlm.nih.gov/pubmed/15972725?dopt=Abstract)
  • Lin SY, Pan HW, Liu SH, Jeng YM, Hu FC, Peng SY, Lai PL, Hsu HC. ASPM is a novel marker for vascular invasion, early recurrence, and poor prognosis of hepatocellular carcinoma. Clin Cancer Res. 2008 Aug 1;14(15):4814-20. doi: 10.1158/1078-0432.CCR-07-5262. (http://www.ncbi.nlm.nih.gov/pubmed/18676753?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/259266)
  • 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. The molecular 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. (http://www.ncbi.nlm.nih.gov/pubmed/19028728?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 healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2011
Published: July 21, 2014