Domain organization of TERT, TPP1, TIN2, TCAB1, PARN, and RTEL1. Selected DC and HH mutations are shown in red, AA mutations are shown in orange, and PF mutations are shown in yellow. Amino acid numbering above the schematics indicates domain boundaries. Shading connecting domains of one protein to another represents protein–protein interactions mediated through the specified domains. The following proteins are described: TERT (Telomerase essential N-terminal domain [TEN], insertion in fingers domain [IFD; purple]). TPP1 (TIN2-binding motif of TPP1 [TBM], N-terminus of the OB [NOB; lavender], TEL patch residues are shown in cyan). TIN2 (TRF1 binding motif [FxLxP; navy blue], DC hotspot represents a cluster of DC mutations in TIN2). Dyskerin (pseudouridine synthase catalytic domain [TruB], RNA-binding domain [PUA]). TCAB1 (each of six WD repeats is indicated in the WD40-repeat domain). PARN (R3H domain [blue] splits the CAF1 nuclease domain [aqua]). RTEL1 (DEAH box [blue], PCNA binding box [PIP box-green], metal-coordinating C4C4 motif thought to bind TRF2 [C4C4 motif]).