TELO2 (OMIM *611140) is a gene located on the 16p13.3 chromosomal region. Its molecular function is carried out through the molecular interactions, as TELO2 cooperates with Telo2-interacting protein 1 and 2 (TTI1, *614425 asnd TTI2, *614,426) to form a heterotrimer called triple T complex (TTT). The TTT macromolecular system, along with chaperone Hsp90 and the R2TP complex, takes part in a bigger supercomplex that acts as a co-chaperone for the maturation and stabilization of a set of six phosphatidylinositol 3-kinase-related protein kinases (PIKKs), which are key regulators of cell proliferation and genome maintenance. The implication of the Triple T complex genes in human pathology points out the crucial importance of the system, that is responsible for checkpoint responses to cellular stress and DNA-damage signaling. In particular, TTI1 provides a platform on which the TELO2 C-terminal domain (CTD) and the TTI2 N- and C-terminal segments bind, recruiting ATM and thus controlling cell survival in response to ionizing radiation.
TELO2 has been recognized to have a role in human disease only in 2016 and only a few patients have been reported. Reported variants are mostly missense, but two sisters with a frameshift variant and one boy with a splice site variant have been described, in all cases the second variant was a missense. The few patients reported do not permit by now to define possible genotype-phenotype correlations, but one report suggest that patients carrying the recurrent c.1826G>A (p.Arg609His) in homozygous state may have a milder presentation.
TELO2