Figure 2.

Mutations of the UTX gene in leukaemia. The UTX (ubiquitously transcribed X chromosome tetratricopeptide repeat protein) gene contains 29 exons (black boxes) that encode a 1401‐amino acid (aa) protein with a molecular weight of 154 kDa. The amino‐terminal region shows six tetratricopeptide repeat (TRP) domains (indicated in orange) and one JmjC domain (aa 1095 to 1258) which contains a catalytic histidine (His1146) (indicated in red). Blue circles depict frameshift mutations (FS) in the JmjC domain in paediatric T‐ALL 177, and white circles depict an in‐frame deletion, a splice acceptor site mutation, and a missense mutation in adult T‐ALL 104. Additional T‐ALL patients have been identified with mutations (brown circles) in the same hotspot region of the JmjC domain 120. These include three frameshift (Val1113‐FS) and two in‐frame insertions/deletions. Other mutations have been found in paediatric B‐ALL (green circles), with one frameshift, two missense, and one nonsense mutations in the JmjC domain, and an additional missense mutation between the TRP and JmjC domains 178. Other mutations have been found in CMML (purple circles) 107, 179 and AML (black circle) patients. A deletion was also detected in a patient with MDS 180. In patients with an inactivated catalytic domain, the mutant protein may have a dominant‐negative activity as the protein‐interacting TRP domain at the N‐terminus is preserved. This may allow the mutant protein to still interact with other proteins, and thus compete with the wild‐type protein (UTX for female and UTY for male) expressed by the other chromosome. Note that this gene also produces many splice variants.