disrupted in schizophrenia 1 protein (DISC1, KIAA0457)

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Function

role in the regulation of multiple aspects of embryonic & adult neurogenesis
required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development & in the adult dentate gyrus of the hippocampus
participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity & CTNNB1 abundance
role as a modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including neuron positioning, dendritic development & synapse formation
inhibits activation of AKT-mTOR signaling upon interaction with CCDC88A
regulates migration of early-born granule cell precursors toward the dentate gyrus during hippocampal development
plays a role, together with PCNT, in the microtubule network formation
interacts with NDEL1
interacts with CCDC88A (via C- terminus); the interaction is direct
interacts with GSK3B
interacts with tubulin alpha, ACTN2, ANKHD1, ATF4, ATF5, CEP63, EIF3S3, MAP1A, NDEL1, PAFAH1B1, RANBP9, SPTBN4, SYNE1 & TRAF3IP1.
interaction with microtubules may be mediated in part by TRAF3IP1.
interacts (via C-terminal) with PCNT

ubiquitous
highly expressed in the dentate gyrus of the hippocampus
also expressed in the temporal cortex & parahippocampal cortex & cells of the white matter
expression rises within the dentate gyrus & temporal cortex from the neonatal period to infancy, declines markedly in adolescence, & declines further with aging

chromosomal translocation t(1;11)(q42.1;q14.3) involving DISC1 segregates with schizophrenia & related psychiatric disorders in a large Scottish family
the truncated DISC1 protein produced by this translocation is unable to interact with ATF4, ATF5 & NDEL1
genetic variation in DISC1 is associated with susceptibility to schizophrenia type 9