1q31.3

ASP,Calmbp1,MCPH5

Primary autosomal recessive microcephaly (MCPH)

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.

Hepatocellular carcinoma

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.

Glioblastoma

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.

Cancers of the uterus and ovary

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.