As BTLA engages HVEM in its first cysteine-rich domain (CRD1) and mutation at the 61 tyrosine to alanine (Y61A) of the HVEM CRD1 domain disrupts the binding to BTLA [13,42,43], we hypothesized that Y61A HVEM could not play a regulatory role in the tumor cell. The gene discussed is BTLA; the disease is neoplasm.