A hypothesis that proposes that defects in PHD2 and PHD3 function may be causal of the symptoms of schizopnrenia.

A defect in the coactivation of HIF1 by PKM2 and PHD3 has been implicated in a familial disorder which can cause autoinflammatory symptoms, connective tissue symptoms and psychosis. It has also been pointed out that a majority of predicted target genes of HIF1 are associated with schizopnrenia, or have altered function or expression in schizopnrenia. PHD2 and PHD3 both regulate HIF1a. Here it is noted that PHD2 (EGLN1) is located at 1q42.2, very close to the location of DISC1 and DISC2, whilst PHD3 (EGLN3) is located at 14q13.1, very close to the location of NPAS3. The disruption of DISC1 and DISC2 genes by a translocation co-segregating with familial schizopnrenia is well known. A mutation in NPAS3 also segregates with schizophrenia in a small family. This raises the interesting possibility that defective PHD2 and PHD3 function could be causal of the symptoms of schizopnrenia.