Mutations that interfere with the active site—the heme group or residues involved in substrate binding—result in a complete loss of enzymatic activity, the salt-wasting type.[36] Studies have shown that mutations in the structure of 21-hydroxylase are related to the clinical severity of congenital adrenal hyperplasia.[37] Cortisol and aldosterone deficits are associated with life-threatening salt-loss (hence salt-wasting), as the steroids play roles in regulating sodium homeostasis. Retaining minimal enzyme activity, the simple-viralizing type is associated with mutations in conserved hydrophobic regions or near the transmembrane domain.