This report describes microcephaly 3, primary, autosomal recessive (MCPH3), which is a subtype of primary microcephaly. The human gene implicated in this disease is CDK5 regulatory subunit associated protein 2 (CDK5RAP2), which plays a role in centrosome function. There is a single fly ortholog, Dmel\cnn, for which classical amorphic and hypomorphic mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
A related fly disease model is described in 'microcephaly, centrosome-SAC dysfunction' (FBhh0000778). In this model, a mutation of Dmel\cnn has been combined with a mutation in a component of the spindle assembly checkpoint (SAC).
[updated Mar. 2018 by FlyBase; FBrf0222196]
Primary microcephaly (MCPH) refers to the clinical finding of a head circumference less than 3 standard deviations below the age- and sex-related mean, present at birth. Primary microcephaly is a static developmental anomaly, distinguished from secondary microcephaly, which refers to a progressive neurodegenerative condition. Microcephaly is a disorder of fetal brain growth; individuals with microcephaly have small brains and almost always have mental retardation; additional clinical features may include short stature or mild seizures (review by Woods et al., 2005; pubmed:15806441). [from MIM:251200; 2016.06.16]
[MICROCEPHALY 3, PRIMARY, AUTOSOMAL RECESSIVE; MCPH3](https://omim.org/entry/604804)
[CDK5 REGULATORY SUBUNIT-ASSOCIATED PROTEIN 2; CDK5RAP2](https://omim.org/entry/608201)
Microcephaly 3 (MCPH3) is caused by homozygous or compound heterozygous mutation in the CDK5RAP2 gene. [from MIM:604804; 2018.03.29]
CDK5RAP2 encodes a regulator of CDK5 (cyclin-dependent kinase 5) activity. The CDK5RAP2 protein is localized to the centrosome and Golgi complex, interacts with CDK5R1 and pericentrin (PCNT), and plays a role in centriole engagement and microtubule nucleation. [Gene Cards, CDK5RAP2; 2018.03.29]
The CDK5RAP2 gene encodes a centrosomal protein that localizes to the spindle poles during mitosis (summary by Hassan et al., 2007, pubmed:17764569; Lizarraga et al., 2010, pubmed:20460369). [from MIM:608201; 2018.03.29]
Many to one: 3 human to 1 Drosophila; all are low-scoring orthologs.
