| Candidate genes | Mutation | Location | RAS-MAPK involvement | References |
---|---|---|---|---|---|
Low penetrance genes | CASC14/NBAT-1 | Loss of function | 6p22 | MAPK1/3 inhibition | [1, 2] |
CASC15 | Â | 6p22 | Â | Â | |
BARD1 | Gain of function | 2q35 | MAPK1a | [3–6] | |
LMO1 | Gain of function | 11p15.4 | MAPK1/3 activation | [7, 8] | |
HSD17B12 | Â | 11p11.2 | Â | Â | |
DUSP12 | NA | 1q23.3 | MAPK1, HRAS inhibition | [9–12] | |
LIN28B | Gain of function | 6q16 | MAPK1/3 activation | [13, 14] | |
HACE1 | Loss of function | 6q16 | MAPK1/3 inhibition | [13, 15, 16] | |
SPAG16 | Â | 2q34 | Â | Â | |
NEFL | Â | 8p21 | Â | Â | |
MLF1/RSRC1 | NA | 3q25 | ARAFa | [17] | |
CPZ | Â | 4p16 | Â | Â | |
CDKN1B | Inhibited by GRB2 through p27Kip1 | 12p13.1 | MAPK1 | [16, 18–22] | |
GRB2 | |||||
SLC16A1 | NA | 1p13.2 | KRASa | [23–27] | |
NRASa | |||||
HRASa | |||||
MSX1 | Gain of function | 4p16.2 | ARAF activation | [28, 29] | |
MMP20 | NA | 11q22.2 | Activation of pathway | [30] | |
KIF15 | NA | 3p21.31 | Activation of pathway | [31–33] | |
High penetrance genes | CHEK2 | Loss of function | 22q12.1 | MAPK1/3 inhibition | [5, 34, 35] |
AXIN2 | Â | 17q24.1 | Â | Â | |
BRCA2 | Loss of function | 13q13.1 | GRB2 | [36–39] | |
SDHB | Â | 1p36.13 | Â | Â | |
SMARCA4 | Loss of function | 19p13.2 | NF1a | [40–42] | |
MAPK1a | |||||
LZTR1 | Loss of function | 22q11.21 | NF1 | [23, 25, 26, 43, 44] | |
NRAS inhibition | |||||
BRCA1 | Loss of function | 17q21.31 | NF1 | [45–48] | |
MAPK3 | |||||
MAPK1 | |||||
NBPF23 | Â | 1q21.1 | Â | Â | |
SEZ6L2/PRRT2 | Â | 16p11.2 | Â | Â | |
APC | Loss of function | 5q22.2 | MAP2K1 inhibition | [39, 49] | |
TP53 | Loss of function | 17p13.1 | MAPK1 | [50–83] | |
HRAS | |||||
GRB2 | |||||
KRAS | |||||
BRAF | |||||
SHC1 | |||||
PTPN11 | |||||
MAP2K1 | |||||
MAP2K2] | |||||
ARAF |