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Another reason is the fact that IDH3, unlike IDH1 or 2, does not catalyze the conversion of 2KG to ICT (the reverse reductive carboxylation reaction), so it is not subject to the gain of function effect seen in monoallelic IDH1 and 2 arginine substitution where, as explained below, the oncometabolite (D)-2HG would be produced from 2KG