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

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]