KIDINS220

Kinase D-interacting substrate of 220 kDa or ARMS (ankyrin repeat-rich membrane spanning) is a scaffold protein that in humans is encoded by the "KIDINS220" gene.
It is a downstream target of neuronal signaling events initiated by neutrophins and ephrins. Additionally, it was shown to have important roles in the immune system by interacting with the B-cell and T-cell receptor.
Molecular biology.
The gene is located on the short arm of chromosome 2 (2p25.1) on the Crick strand. It is 116,550 bases in length. It encodes a transmembrane protein that is preferentially expressed in the nervous system. The protein acts as a receptor for the CRKL-C3G complex. Binding this complex results in Rap1-dependent sustained ERK activation. This, in turn, interacts with several pathways the effects of which are under active investigation.
Clinical importance.
Heterozygous mutations of this gene have been suggested as a cause of a syndrome consisting of spastic paraplegia, intellectual disability, nystagmus and obesity. Knock out mice with homozygous mutations have non-viable offspring with enlarged cerebral ventricles. A consanginous couple has been reported who suffered from repeated miscarriages in whom homozygous mutations of this gene were found. Post mortum showed enlarged cerebral ventricles and contracted limbs. 