Schematic of the telomere and functions of the proteins affected in TBDs. Protein function and the reported consequences of mutations in the respective gene are summarized in Table 2. Components are grouped approximately based on their function. Shown in green: the components of the telomerase enzyme complex (DKC1, TERC, TERT, NAF1, NOP10, NHP2), telomerase or hTR regulators (TCAB1, PARN, and ZCCHC8), and regulator of telomere elongation helicase 1 (RTEL1). Dark blue: the shelterin (TPP1, TIN2, and POT1) and the CST (CTC1 and STN1) complexes. Red: the proteins primarily involved in DNA repair. Red line: Apollo interacts with TRF1. NPM1 is involved in ribosomal RNA maturation and interacts with NOP10 and NHP2. MDM4 is not shown because it does not directly act at the telomere. Gray symbols: known key telomere biology proteins not yet attributed to human disease (GAR1 in telomerase complex; TRF1, TRF2, RAP1 in shelterin; TEN1 in CST). Yellow asterisk: autosomal dominant; light-blue asterisk: autosomal recessive; orange asterisk: X-linked recessive. Complete protein name (gene name): Apollo (DCLRE1B); 1, CTC1, conserved telomere maintenance component 1 (CTC1); DKC1, dyskerin (DKC1); MDM4, MDM4 regulator or p53 (MDM4); NAF1, nuclear assembly factor 1 ribonucleoprotein (NAF1); NHP2, NOLA2 nucleolar protein family A, member 2 (NHP2); NOP10, nuclear protein family A, member 3 (NOP10); NPM1, nucleophosmin 1 (NPM1); PARN, poly (A)-specific ribonuclease (PARN); POT1, protection of telomeres 1 (POT1); RPA1, replication protein A1 (RPA1); RTEL1, regulator of telomere elongation helicase 1 (RTEL1); STN1, CST complex subunit (STN1); TCAB1, telomere Cajal body–associated protein 1 (WRAP53); TERC, hTR, human telomerase RNA component (TERC); TERT, human telomerase reverse transcriptase (TERT); TIN2, TRF1-interacting nuclear factor 2 (TINF2); TPP1: telomere protection protein 1 (ACD); ZCCHC8: Zinc finger CCHC domain-containing protein 8 (ZCCHC8).

Figure adapted with permission from Niewisch and Savage.¹