Table 1.
Mutations in KATP channel genes KCNJ11 and ABCC8 causing hyperinsulinism of infancy
| Genotype | Position in structure | Molecular mechanism | Phenotype |
|---|---|---|---|
| Kir6.2 subunit KCNJ11 | |||
| Y12Δ | N terminus | Immature Kir6.2 subunits | HI |
| R34H | Interface between Kir6.2 subunits | HI | |
| F55L | Interface with SUR1 subunits | HI | |
| K67N | Slide helix | HI | |
| W91R | Linker between TM1 and pore region | HI | |
| A101D | Linker between TM1 and pore region | HI | |
| S116P | Pore region | HI | |
| G134A | Linker between pore region and TM2 | HI | |
| R136L | Linker between pore region and TM2 | HI | |
| L147P | TM2 | HI | |
| A187V | ATP-binding site | HI | |
| P254L | ATP-binding site | HI | |
| H259R | ATP-binding site | Reduced trafficking of the channel | HI |
| P266L | C terminus | HI | |
| E282 K | C terminus | HI | |
| T294M | Gating | Reduced channel Po | HI |
| R301H | Gating | HI | |
| C344Δ | C terminus | Immature Kir6.2 subunits | HI |
| SUR1 subunit ABCC8 | |||
| G70E | Linker between TM1 and TM2 | HI | |
| R74Q/W | Linker between TM1 and TM2 | HI | |
| G111R | TM3 | HI | |
| A116P | TM3 | HI | |
| H125Q | Linker between TM3 and TM4 | HI | |
| V167L | TM5 | HI | |
| V187D | TM5 | HI | |
| N188S | TM5 | HI | |
| Q219Δ | Linker between TM5 and TM6 | Immature SUR1 subunits | HI |
| R248Δ | Linker between TM5 and TM6 | Immature SUR1 subunits | HI |
| N406D | Linker between TM7 and TM8 | HI | |
| N418R | Linker between TM7 and TM8 | HI | |
| L508P | Linker between TM9 and TM10 | HI | |
| F591L | NBD1 | HI | |
| R598Δ | NBD1 | Immature SUR1 subunits | HI |
| R620C | NBD1 | HI | |
| G716V | Walker A in NBD1 | HI | |
| C717Δ | Walker A in NBD1 | Immature SUR1 subunits | HI |
| R837Δ | NBD1 | Immature SUR1 subunits | HI |
| R842G | NBD1 | HI | |
| K890T | NBD1 | HI | |
| Q954Δ | NBD1 | Immature SUR1 subunits | HI |
| S957F | NBD1 | HI | |
| R999Δ | NBD1 | Immature SUR1 subunits | HI |
| T1139M | Linker between TM13 and TM14 | HI | |
| R1215Q/W | Linker between TM15 and TM16 | HI | |
| K1337N | NBD2 | HI | |
| W1339Δ | NBD2 | Immature SUR1 subunits | HI |
| G1343E | NBD2 | HI | |
| R1353P/H | NBD2 | HI | |
| V1361M | NBD2 | HI | |
| G1379R | Walker A in NBD2 | Reduced Mg–nucleotide binding | HI |
| G1382S | Walker A in NBD2 | Reduced Mg–nucleotide binding | HI |
| S1387F | NBD2 | HI | |
| F1388Δ | NBD2 | Immature SUR1 subunits | HI |
| R1394H | NBD2 | Impaired trafficking of SUR1 subunits | HI |
| G1401D | NBD2 | HI | |
| R1419H | NBD2 | HI | |
| R1421C | NBD2 | Reduced Mg–nucleotide binding | HI |
| R1437Q | NBD2 | HI | |
| A1458T | NBD2 | HI | |
| G1479R | NBD2 | Reduced Mg–nucleotide binding | HI |
| A1493T | NBD2 | HI | |
| R1494Q/W | NBD2 | HI | |
| E1507K | Walker B in NBD2 | Reduced Mg–nucleotide binding | HI |
| L1544P | NBD2 | Impaired trafficking of SUR1 subunits | HI |
| V1551D | NBD2 | Reduced Mg–nucleotide binding | HI |
| L1552V | NBD2 | Reduced Mg–nucleotide binding | HI |
| G1555S | C terminus | HI |
Abbreviations: HI, hyperinsulinism of infancy; SUR1, sulfonylurea receptor 1.