We identified an uncharacterized gene, UBE2QL1, that was disrupted by a t(5;19)(p15.3;q12) associated with a familial predisposition to RCC, and demonstrated that UBE2QL1 has tumor suppressor activity and is inactivated in a subset of sporadic RCC by promoter region hypermethylation and/or deletions. The gene discussed is UBE2QL1; the disease is renal cell carcinoma.