DAXX mutations identified in cancer are frequently nonsense and frameshift mutations that result in premature protein truncation. Mutant DAXX proteins are frequently lost or mis-localized and are usually undetectable in the nucleus. DAXX contains an ATRX-binding region that maps to PAH domains of DAXX, PAH1 and PAH2, which are located in the N-terminal portion of DAXX. At least the PAH1 domain is needed for binding to ATRX, and a recombinant construct consisting of amino acids 1-160 of DAXX, which includes the PAH1 domain, is able to bind to ATRX, but the binding is stronger if PAH2 domain is also included (if the recombinant DAXX construct consists of amino acids 1-260) (Tang et al. 2004). Minimally, amino acids 55-144 are required for DAXX binding to ATRX (Wang et al. 2017). All DAXX truncation mutants in which the stop codon occurs upstream of the amino acid 144 are annotated as candidate loss-of-function mutants. These include the following nonsense mutants:
DAXX K56*
DAXX E104*
DAXX C106*
DAXX S138*.
DAXX frameshift mutants in which the frameshift occurs upstream of the codon 144 are also annotated as candidates:
DAXX H26Tfs*118
DAXX A36Qfs*108
DAXX R48Vfs*93
DAXX E72Nfs*72
DAXX C74*
DAXX L98Vfs*13
DAXX A103Sfs*40.
Missense mutants of DAXX have not been functionally tested in the context of the full-length protein, just in the context of the DAXX fragment that consists of amino acids 55-144 (Wang et al. 2017) and are not shown here.