MCPH1
Domain
BRCT domain 1 is required to prevent abnormal chromosome condensation. It binds directly to the SWI-SNF chromatin remodeling complex (PubMed:19925808).
BRCT domains 2 and 3 recognize phosphoserine/phosphothreonine marks on proteins with high selectivity, and mediate interaction with phosphorylated CDC27. They also mediate the dual recognition of phosphoserine and phosphotyrosine in the C-terminal tail of histone H2AX (PubMed:22139841, PubMed:22908299).
Function
Implicated in chromosome condensation and DNA damage induced cellular responses. May play a role in neurogenesis and regulation of the size of the cerebral cortex.
Involvement in disease
Microcephaly 1, primary, autosomal recessive
MCPH1
A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals have mild to severe intellectual disability. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. Some MCHP1 patients also present growth retardation, short stature, and misregulated chromosome condensation as indicated by a high number of prophase-like cells detected in routine cytogenetic preparations and poor-quality metaphase G-banding.
None
The disease is caused by variants affecting the gene represented in this entry.
Tissue Specificity
Expressed in fetal brain, liver and kidney.
Cellular localization
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
Alternative names
Microcephalin, MCPH1