Table 1.
Summary of key functionally validated FOXA1 coding mutations
| Type | Location | Mutation | Key functional alterations | Ref |
|---|---|---|---|---|
| Missense | FKHD | I176M | Increased nuclear mobility; higher activation of AR signaling; increased cell growth in androgen-depleted condition | (Parolia et al. 2019) |
| FKHD | R219C, R219S | Decreased transcriptional activity; increased growth of mouse organoid; preference for non-canonical FOXA1 binding motif; promotes EMT | (Adams et al. 2019) | |
| FKHD | D226N, D226G | Increased growth of mouse organoid; mixed results on the effect of AR activity; promotes EMT | (Adams et al. 2019; Gao et al. 2019; Xu et al. 2019) | |
| FKHD Wing2 | H247Q, H247R, H247Y | Increased growth of mouse organoid; mixed results on the effect of AR activity; promotes EMT | (Adams et al. 2019; Gao et al. 2019) | |
| FKHD Wing2 | M253K | Increased growth of mouse organoid; mixed results on the effect of AR activity; reduced chromatin binding; promotes EMT; increased cell growth in androgen-depleted condition | (Adams et al. 2019; Gao et al. 2019; Xu et al. 2019) | |
| FKHD Wing2 | Y259C, Y259S | Increased transcriptional activity; increased growth of mouse organoid | (Adams et al. 2019) | |
| FKHD Wing2 | R261G, R261C | Increased nuclear mobility; higher activation of AR signaling; increased cell growth in androgen-depleted condition; increased growth of mouse organoid | (Adams et al. 2019; Parolia et al. 2019) | |
| FKHD Wing2 | F266L, F266S | Increased growth of mouse organoid; mixed results on the effect of AR activity; reduced chromatin binding; increased cell growth in androgen-depleted condition; promotes EMT | (Adams et al. 2019; Xu et al. 2019) | |
| Indels | FKHD Wing2 | ΔM253–N256 | Increased transcriptional activity; increased growth of mouse organoid | (Adams et al. 2019) |
| FKHD Wing2 | ΔF254/E255 | Increased transcriptional activity; increased growth of mouse organoid | (Adams et al. 2019) | |
| FKHD Wing2 | FENG254-7>C | Reduced chromatin binding; increased cell growth in androgen-depleted condition; promotes EMT | (Xu et al. 2019) | |
| FKHD Wing2 | ΔR265-Q271 | Increased nuclear mobility; higher activation of AR signaling; increased cell growth in androgen-depleted condition | (Parolia et al. 2019) | |
| Frameshift truncations | C-term | P358fs | Higher DNA-binding affinity; increased invasion through activation of WNT pathway | (Parolia et al. 2019) |
| C-term | G275X | Increased transcriptional activity; increased growth of mouse organoid | (Adams et al. 2019) |