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ASPM (asp (abnormal spindle) homolog, microcephaly associated (Drosophila))

Written2009-12Shian-Yang Peng, Shih-Yeh Lin, Hey-Chi Hsu
Department of General Education, National Taipei College of Nursing, Taipei 100, Taiwan, Republic of China (SYP); Graduate Institute of Pathology, College of Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan, Republic of China (SYL); Department of Pathology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan, Republic of China (HCH)

(Note : for Links provided by Atlas : click)


HGNC Alias symbCalmbp1
HGNC Previous nameMCPH5
HGNC Previous namemicrocephaly, primary autosomal recessive 5
 asp (abnormal spindle)-like, microcephaly associated (Drosophila)
 asp (abnormal spindle) homolog, microcephaly associated (Drosophila)
 abnormal spindle microtubule assembly
LocusID (NCBI) 259266
Atlas_Id 44463
Location 1q31.3  [Link to chromosome band 1q31]
Location_base_pair Starts at 197084127 and ends at 197146669 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping ASPM.png]
Local_order Several genes flanking ASPM arranged by an order of centromere to telomere are:
KCNT2 (1q31.3) (potassium channel, subfamily T, member 2)
CFH (1q32) (complement factor H)
CFHR3 (1q32) (complement factor H-related 3)
CFHR1 (1q32) (complement factor H-related 1)
CFHR4 (1q32) (complement factor H-related 4)
CFHR2 (1q31-q32.1) (complement factor H-related 2)
CFHR5 (1q22-q23) (complement factor H-related 5)
F13B (1q31-q32.1) (coagulation factor XIII, B polypeptide)
ASPM (1q31) (asp (abnormal spindle) homolog, microcephaly associated (Drosophila))
ZBTB41 (1q31.3) (zinc finger and BTB domain containing 41)
LOC127011 (1q31.3) (similar to ATPase, H+ transporting, lysosomal accessory protein 2)
MRPS21P3 (1q31.2) (mitochondrial ribosomal protein S21 pseudogene 3)
CRB1 (1q31-q32.1) (crumbs homolog 1 (Drosophila))
C1orf218 (1q31.3) (chromosome 1 open reading frame 218)
DENND1B (1q31.3) (DENN/MADD domain containing 1B)
LOC730232 (1q31.3) (similar to eukaryotic translation elongation factor 1 alpha 1)
LOC100129017 (1q31.3) (hypothetical LOC100129017)
C1orf53 (1q31.3) (chromosome 1 open reading frame 53)
LHX9 (1q31-q32) (LIM homeobox 9)
LOC647195 (1q31.3) (hypothetical LOC647195)
NEK7 (1q31.3) (NIMA (never in mitosis gene a)-related kinase 7)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
WWOX (16q23.1)::ASPM (1q31.3)


  Genomic diagram of ASPM gene. Exons are represented by boxes on the diagram.
Description ASPM, maps to NC_000001.10 in human genome, contains 28 exons with a 10,434 base pairs ORF (NCBI GenBank accession number AF509326), spanning a region of 62,568 base pairs at chromosome 1q31.
Transcription ASPM encodes a 10906 bps mRNA, (NM_018136.4), in a telomeric to centromeric orientation and the coding region is from 258 bp to 10961bp (10434 bp). 5' part of exon 1 and 3' part of exon 28 are non-coding. The 28 exons of ASPM mRNA are 554, 144, 1480, 105, 147, 246, 68, 142, 131, 176, 146, 86, 222, 208, 143, 129, 195, 4755, 167, 97, 210, 150, 192, 193, 155, 177, 170, 300 base pairs, respectively.
Pseudogene None.


  ASPM protein contains 2 calponin homology (CH) domains and 81 IQ repeats domain. Total 81 distinct IQ motifs were found at position 1273 to 3243. Numbers indicate the amino acid numbers.
Description The 10434 bps ORF of ASPM mRNA translates a 3477 amino acid protein with a calculated molecular weight of 409.8 kDa. The main ASPM isoform protein, from N-terminal, begins with a microtubule binding domain, followed by two calponin homology (CH) domains, which are possibly responsible for transportation of the ASPM protein to the spindle poles. The third part is IQ (I for isoleucine, Q for glutamine) repeats region which is the calmodulin binding domains. The numbers of IQ repeats are identified up to 81, at position 1273 to 3243. The C-terminal of ASPM is an armadillo-like domain of unknown function.
Expression ASPM transcripts were detected in a variety of human embryo tissues (brain, bladder, colon,heart, liver, lung, skeletal muscle, skin, spleen and stomach), and in adult tissues except for the adult brain, but with much lower amount.
ASPM isoforms were generated by alternative splicing. The brain-specific isoform, main ASPM isoform corresponds to a 3477 amino acid residue protein (410 kDa) containing 81 IQ motifs. Alternatively spliced human ASPM variants code for different numbers of IQ domains. Two major ASPM transcripts with sizes of 10.3 and 5.7 kb were identified in all tissues analyzed. The spliced variants of ASPM with variable sizes were also detected in fetus tissue.
Localisation ASPM protein, a component of the mitotic spindle, localizes to the centrosome in interphase and to the spindle poles from prophase through telophase.
Function ASPM is a spindle pole/centrosome protein, essential for neurogenic mitosis and possibly controlling the fate-switch to asymmetric cell division through the position of the centrosome at mitosis. The brain-specific main ASPM isoform protein appears to be pivotal for the expansion of cerebral cortical size. Other spliced variants contain different IQ domains or lacking both CH domains and a part of the IQ motifs may be potentially with different functions. One of the smaller proteins detected in cell extracts may be the ASPM product required for mitosis by all dividing cells.
Homology According to protein identities compared with Human ASPM:
Pan troglodytes: ASPM; (3443/3477, 99%)
Canis lupus familiaris: ASPM; (2738/3392, 80%)
Bos taurus: ASPM; (2557/3484, 73%)
Mus musculus: Aspm; (1882/2948, 63%)
Rattus norvegicus: Aspm; (1851/2939, 62%)
Danio rerio: aspm; (1390/3554, 39%)


  Mutation of ASPM in MCPH. According to Nicholas et al. 2009, all reported autosomal recessive primary microcephaly (MCPH) mutations in ASPM have been presented in this table by different kind of mutations, including nonsense mutations, deletions, insertions and mutations in the splicing region. The reference sequence of mutation sites is according to NM_018136.3.

Implicated in

Entity Primary autosomal recessive microcephaly (MCPH)
Note Primary autosomal recessive microcephaly is a neurodevelopment disorder due to the consequence of deficient neurogenesis within the neurogenic epithelium, resulting in congenital microcephaly (reduced brain size) and mental retardation. MCPH is the consequence of impairment in mitotic spindle regulation in cortical progenitors due to mutations in ASPM.
Homozygous mutations in the ASPM gene, located at MCPH5 locus on chromosome 1q31, are the most common cause of MCPH particularly in the Pakistani population. ASPM mutations are restricted to individuals with an MCPH, no defects other than microcephaly are found in patients carrying mutations in this gene. So far, the phenotypic differences in people with different versions of these genes were not found.
Entity Hepatocellular carcinoma
Note ASPM, a component of the mitotic spindle, is shown to express in many human malignant cells nearly and all transformed human cell lines, suggesting that ASPM play an important role in cell proliferation in tumorigenesis.
ASPM mRNA was overexpressed in human hepatocellular carcinoma (HCC), but was very low or undetectable in adult liver, and in benign hepatic tumors, such as hepatocellular adenoma and focal nodular hyperplasia. The overexpression of ASPM correlated with higher-grade (grade II-IV), high-stage (stage IIIA-IV which had vascular invasion) and poor prognosis of HCC. In addition, ASPM overexpression is the most important molecular factor associated with ETR (early tumor recurrence) (intrahepatic tumor recurrence and/or distant metastasis within 12 months after HCC tumor resection), and could be used as a molecular marker predicting enhanced invasive/metastatic potential of HCC.
Entity Glioblastoma
Note ASPM is essential for normal mitotic spindle function in embryonic neuroblasts, and is recognized as a critical regulator of brain size, it may play a role in promoting neuroblast proliferation. Using gene coexpression module in glioblastoma, ASPM was identified as a key gene of glioblastoma, its overexpression was demonstrated in glioblastoma relative to normal brain. siRNA-mediated ASPM knockdown inhibits neural stem cell self renewal and turn forward neural stem cell differentiation. ASPM knockdown also inhibits cell growth of U87-EGFRvIII cells (glioblastoma cells) and the low passage explant culture from a glioblastoma patient. Those result suggesting that ASPM is a potential molecular target in glioblastoma that resulting in the overexpression of ASPM in glioblastoma.
Entity Cancers of the uterus and ovary
Note From high-density oligonucleotide microarrays and using quantitative real-time RT-PCR, ASPM is found more highly expressed in cancers of the uterus and ovary when compared with their normal endometrium counterparts.


ASPM is a major determinant of cerebral cortical size.
Bond J, Roberts E, Mochida GH, Hampshire DJ, Scott S, Askham JM, Springell K, Mahadevan M, Crow YJ, Markham AF, Walsh CA, Woods CG.
Nat Genet. 2002 Oct;32(2):316-20. Epub 2002 Sep 23.
PMID 12355089
Protein-truncating mutations in ASPM cause variable reduction in brain size.
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.
Am J Hum Genet. 2003 Nov;73(5):1170-7. Epub 2003 Oct 21.
PMID 14574646
Genetic studies of autosomal recessive primary microcephaly in 33 Pakistani families: Novel sequence variants in ASPM gene.
Gul A, Hassan MJ, Mahmood S, Chen W, Rahmani S, Naseer MI, Dellefave L, Muhammad N, Rafiq MA, Ansar M, Chishti MS, Ali G, Siddique T, Ahmad W.
Neurogenetics. 2006 May;7(2):105-10. Epub 2006 Apr 21.
PMID 16673149
Novel protein-truncating mutations in the ASPM gene in families with autosomal recessive primary microcephaly.
Gul A, Tariq M, Khan MN, Hassan MJ, Ali G, Ahmad W.
J Neurogenet. 2007 Jul-Sep;21(3):153-63.
PMID 17849285
Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target.
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.
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17402-7. Epub 2006 Nov 7.
PMID 17090670
The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein.
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.
Hum Mol Genet. 2005 Aug 1;14(15):2155-65. Epub 2005 Jun 22.
PMID 15972725
Genetic analysis of primary microcephaly in Indian families: novel ASPM mutations.
Kumar A, Blanton SH, Babu M, Markandaya M, Girimaji SC.
Clin Genet. 2004 Oct;66(4):341-8.
PMID 15355437
ASPM is a novel marker for vascular invasion, early recurrence, and poor prognosis of hepatocellular carcinoma.
Lin SY, Pan HW, Liu SH, Jeng YM, Hu FC, Peng SY, Lai PL, Hsu HC.
Clin Cancer Res. 2008 Aug 1;14(15):4814-20.
PMID 18676753
The molecular landscape of ASPM mutations in primary microcephaly.
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.
J Med Genet. 2009 Apr;46(4):249-53. Epub 2008 Nov 21.
PMID 19028728
ASPM and citron kinase co-localize to the midbody ring during cytokinesis.
Paramasivam M, Chang YJ, LoTurco JJ.
Cell Cycle. 2007 Jul 1;6(13):1605-12. Epub 2007 Apr 27.
PMID 17534152
ASPM mutations identified in patients with primary microcephaly and seizures.
Shen J, Eyaid W, Mochida GH, Al-Moayyad F, Bodell A, Woods CG, Walsh CA.
J Med Genet. 2005 Sep;42(9):725-9.
PMID 16141009
The abnormal spindle-like, microcephaly-associated (ASPM) gene encodes a centrosomal protein.
Zhong X, Liu L, Zhao A, Pfeifer GP, Xu X.
Cell Cycle. 2005 Sep;4(9):1227-9. Epub 2005 Sep 13.
PMID 16123590


This paper should be referenced as such :
Peng, SY ; Lin, SY ; Hsu, HC
ASPM (asp (abnormal spindle) homolog, microcephaly associated (Drosophila))
Atlas Genet Cytogenet Oncol Haematol. 2010;14(9):861-865.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)ASPM   19048
Entrez_Gene (NCBI)ASPM    assembly factor for spindle microtubules
AliasesASP; Calmbp1; MCPH5
GeneCards (Weizmann)ASPM
Ensembl hg19 (Hinxton)ENSG00000066279 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000066279 [Gene_View]  ENSG00000066279 [Sequence]  chr1:197084127-197146669 [Contig_View]  ASPM [Vega]
ICGC DataPortalENSG00000066279
Genatlas (Paris)ASPM
SOURCE (Princeton)ASPM
Genetics Home Reference (NIH)ASPM
Genomic and cartography
GoldenPath hg38 (UCSC)ASPM  -     chr1:197084127-197146669 -  1q31.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ASPM  -     1q31.3   [Description]    (hg19-Feb_2009)
GoldenPathASPM - 1q31.3 [CytoView hg19]  ASPM - 1q31.3 [CytoView hg38]
Genome Data Viewer NCBIASPM [Mapview hg19]  
OMIM605481   608716   
Gene and transcription
Genbank (Entrez)AF509326 AK001379 AK001380 AK001411 AK095892
RefSeq transcript (Entrez)NM_001206846 NM_018136
Consensus coding sequences : CCDS (NCBI)ASPM
Gene ExpressionASPM [ NCBI-GEO ]   ASPM [ EBI - ARRAY_EXPRESS ]   ASPM [ SEEK ]   ASPM [ MEM ]
Gene Expression Viewer (FireBrowse)ASPM [ Firebrowse - Broad ]
GenevisibleExpression of ASPM in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)259266
GTEX Portal (Tissue expression)ASPM
Human Protein AtlasENSG00000066279-ASPM [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)ASPM
Human Protein Atlas [tissue]ENSG00000066279-ASPM [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed104 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:12:46 CEST 2021

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