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Chunk #27 — Discussion

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Expression of ZNF804A in human brain and alterations in schizophrenia, bipolar disorder, and major depressive disorder: a novel transcript fetally regulated by the psychosis risk variant rs1344706.
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The presence of ZNF804A immunoreactivity indicates that the gene is not only transcribed but also translated in human brain. ZNF804A immunoreactivity was not concentrated in the nucleus as expected for a classic transcription factor and as reported in rodent neural progenitors.9 Its abundance in the cytoplasm suggests additional roles for ZNF804A in human brain; it also raises the possibility of cross-reactivity of the antibody to another protein, although this is unlikely given the experimental controls used. Neither rs1344706 nor schizophrenia affected our measures of ZNF804A immunoreactivity, so the penetrance of genotype and diagnostic effects through to ZNF804A protein remains to be determined. In any event, understanding the pathophysiological significance of ZNF804A is hindered by uncertainty about the translation and function of ZNF804AE3E4. The variant is predicted to encode a 123-kDa protein; although no separate band of this size was seen on Western blots, it could be subsumed within the approximately 137-kDa band corresponding to full-length ZNF804A if ZNF804AE3E4 undergoes posttranslational modifications that increase its apparent molecular weight. If it is translated, ZNF804AE3E4 may well contribute to the non–transcription factor–related functions