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Mechanism of HSD3B1 1245 A→C in the adrenal-permissive phenotype. A→C at HSD3B1 position 1245 results in Asn→Thr at amino acid 367. This change renders the enzyme resistant to ubiquitination and proteasome degradation, leading to protein buildup and increased flux from DHEA to AD. This leads to increased DHT synthesis and ultimately hastens progression to CRPC.
