Table 1. Major genes implicated in autosomal-dominant forms of FTD.
Genes implicated in ≥1% of familial FTD cases are listed in descending order of mutation frequency in cohorts of European ancestry. Estimated mutation frequency data are derived from sources indicated within the main text. Estimated numbers of pathogenic (including presumptive pathogenic) mutations are from the Alzheimer Disease & Frontotemporal Dementia Mutation Database (http://www.molgen.ua.ac.be/ADmutations/default.cfm?MT=1&ML=6&Page=StatPerGene) and [12,13,39].
| 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
A subset of these mutations are implicated in ALS or ALS-FTD (e.g., TARDBP mutations). Pathogenicity is not established for all mutations.
b
Indicates variable-length hexanucleotide repeat expansions in C9ORF72.