E4F1 and ZNF148 are transcriptional activators of the -57A > C and wild-type promoter.

Point mutations within the promoter are the most recurrent somatic noncoding mutations identified across different cancer types, including glioblastoma, melanoma, hepatocellular carcinoma, and bladder cancer. They are most abundant at -146C > T and -124C > T, and rarer at -57A > C, with the latter originally described as a familial case, but subsequently shown also to occur somatically. All three mutations create de novo E26-specific (ETS) binding sites and result in activation of the gene, allowing cancer cells to achieve replicative immortality.