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Table 1 Summary of known MCPH genes, their location and role.

From: Molecular genetics of human primary microcephaly: an overview

Locus Gene Cytoband Cellular location Role/effect on brain development References
MCPH1 Microcephalin 8p23.1 Nucleus Involved in chromosomal condensation, reduced MCPH1 enhances the production of early born neurons, which comprise deep layers (IV–VI), and reduces the late-born neurons, which produce the thinner outer cortex layer (II–III). [6, 27]
MCPH2 WDR62 19q13.12 Nucleus/Centrosomes/Neuronal precursors/Post-mitotic neurons Cerebral cortical development, proliferation and migration of neuronal precursors, mutation in WDR62 affects its role in proliferating and migrating neural precursors and causes severe brain malformations. [13, 30]
MCPH3 CDK5RAP2 9q33.2 Centrosome Regulates microtubule function, mutation in CDK5RAP2 reduces the progenitor pool/decreases the number of neurons and reduces cell survival. [35, 36, 38, 88]
MCPH4 CASC5 15q15.1 Kinetochore Vital for the spindle checkpoint of the mitotic cycle, CASC5 underscores the role of kinetochore integrity in the proper volumetric development of the human brain. [40, 41]
MCPH5 ASPM 1q31.3 Pericentrosomal Orientation of mitotic spindles during embryonic neurogenesis, ASPM mutations can decrease the size of the brain by influencing the orientation of the mitotic spindle. [57, 54, 14]
MCPH6 CENPJ 13q12.12 Centrosome/neuroepithelium of the frontal cortex Controls centriole length/microtubule function, its deletion causes an increased incidence of multiple spindle poles, apoptosis and mitosis arrest [63, 64]
MCPH7 STIL 1p33 Pericentrosomal Apoptosis regulator/cell cycle progression, its mutation in zebrafish causes an embryonic lethal defect, and STIL knockout mice (Sil-/-) exhibit numerous developmental abnormalities/decreased size/defective midline neural tube. [72, 69, 68]
MCPH8 CEP135 4q12 Centrosome Maintains organisation/structure of the centrosome, CEP135 knockdown showed decreased growth rate/disorganised microtubules. [72, 70, 20]
MCPH9 CEP152 15q21.1 Centrosome Centriole duplication/shape to cell/polarity/motility, conversion of glutamine into proline disturbs potential coiled-coiled protein domain/reduced head size. [76, 77]
MCPH10 ZNF335 20q13.12 Nucleus Progenitor cell division/differentiation, mutated ZNF335 gene causes degeneration of neurons, knockdown of ZNF335 caused a small brain size with an absent cortex/disrupted proliferation and differentiation of neuronal cells. [78]
MCPH11 PHC1 12p13.31 Nucleus Regulates cell cycle, PHC1 mutation highlights the role of chromatin remodelling in the pathogenesis of Primary Microcephaly. [80]
MCPH12 CDK6 7q21.11 Cytoplasmic/nuclear Controls cell cycle/organises microtubules, CDK6 mutation affects apical neuronal precursor cells proliferation/reduces progenitor pool/decreases neuronal production/primary microcephaly. [83]
  1. Abbreviations. MCPH: Autosomal recessive primary microcephaly; MCPH1: Microcephalin; WDR62: WD repeat-containing protein 62; CDK5RAP2: Cyclin dependent kinase-5 regulatory subunit associated protein; CASC5: Cancer susceptibility candidate-5; ASPM: Abnormal spindle like primary microcephaly; CENPJ: Centromere-associated protein J; STIL:SCL/TAL1 interrupting locus; CEP135: Centrosomal protein 135; CEP152: Centrosomal protein 152; ZNF335: Zinc Finger Protein 335; PHC1: Polyhomeotic-like protein 1; CDK6: Cyclin-dependent kinase 6.