A germline mutation affecting exon 1beta of the CDKN2A locus is associated with a familial melanoma syndrome. The mutation represents an insertion of 16 nucleotides (CGGCCCGCCGCGAGTG) between coding bases 60 and 61 in exon 1beta. This insertion results in a frameshift, starting at arginine codon at position 21 of p14ARF and ending with a premature stop codon at position 67. The mutant protein p14ARF R21RfsTER47 (p14ARF 60ins16) is unable to translocate to the nucleus and stabilize TP53 (Rizos, Puig et al. 2001).
Loss of function of p14ARF R21RfsTER47 [cytosol]