Table 1. Major genes implicated in autosomal-dominant forms of FTD.
Gene | Chr. | Protein | Protein function | Mutation freq. in familial FTD | Mutation freq. in sporadic FTD | # Pathogenic mutationsa |
---|---|---|---|---|---|---|
C9ORF72 | 9p21.2 | C9ORF72 | Lysosomal homeostasis | 20–30% | 6% | b |
GRN | 17q21.31 | Progranulin | Lysosomal homeostasis; inflammation | 5–25% | 5% | 79 |
MAPT | 17q21.31 | Microtubule-associated protein tau | Microtubule stabilization and assembly | 5–20% | 0–2% | >50 |
TBK1 | 12q14.2 | Serine/threonine-protein kinase TBK1 | Regulator of autophagy and inflammation | 3% | 2–4% | 28 |
SQSTM1 | 5q35.3 | p62 (Sequestosome-1) | Selective autophagy receptor | 1–3% | 1–3% | ~20 |
TARDBP | 1p36.22 | TAR DNA-binding protein 43 (TDP-43) | RNA processing and metabolism | 1% | 1% | 33 |
A subset of these mutations are implicated in ALS or ALS-FTD (e.g., TARDBP mutations). Pathogenicity is not established for all mutations.
Indicates variable-length hexanucleotide repeat expansions in C9ORF72.