Somatic nonsynonymous mutations in conserved residues of the JAK1 gene. (A,C) Electropherograms of matched tumor and germline samples from 2 patients with AML. Heterozygous mutations are indicated by double peaks () consistently detected in both forward and reverse sequencing reactions but not present in the germline samples. (B,D) Change of amino acid sequences as a result of mutations. (E) Schematic diagram of JAK1 protein structure. Somatic mutations are indicated by arrows. The Thr478 residue resides in the β2 strand of the SH2 (JH3-JH4) domain near the phospho-tyrosine binding site of this domain. The Val623 residue resides in the β3 strand of the pseudo-kinase (JH2) domain in close proximity to the G-loop binding site of this domain. (F) Alignment of peptide sequences of conserved JAK1 residues. Both JAK1 mutations affect residues that are highly conserved throughout evolution.