Table 2.
All Missense Mutations of FZD4 in FEVR Patients
| Domain and Amino Acid Positions | Protein Change | Wnt Activity | Membrane Localization | Norrin Binding | DVL2 Recruitment | Reference |
|---|---|---|---|---|---|---|
| Signal peptide (1-36) | ||||||
| P11E | 47 | |||||
| G22E | 48 | |||||
| P33S | Affected | 29 | ||||
| G36D | 49 | |||||
| G36N | Affected | 29 | ||||
| Before loop I (37-53) | ||||||
| E40Q | 50 | |||||
| C45R | 51 | |||||
| C45S | 51 | |||||
| C45Y | Decreased | Affected | Affected | 27 | ||
| S51T | 43 | |||||
| C53S | 51 | |||||
| Loop I (54-59) | ||||||
| G57C | 43 | |||||
| G57R* | 25 | |||||
| Y58C* | Decreased | N.C. | Affected | 27 | ||
| Between loop I and loop II (60-104) | ||||||
| T61I | 21 | |||||
| H69Y | Affected | 29 | ||||
| A75T | 51 | |||||
| A75G | 21 | |||||
| C90R | 51 | |||||
| S91F* | This study | |||||
| Q95L | 52 | |||||
| C99S | Increased | N.C. | 53 | |||
| V103E* | This study | |||||
| Loop II (105-114) | ||||||
| M105V* | N.C./Affected | N.C. | 29, 44 | |||
| M105R | Decreased | Affected | 28 | |||
| M105T | Affected | 29 | ||||
| C106G | 54 | |||||
| C106S | 21 | |||||
| I114T | 55 | |||||
| I114S* | 56 | |||||
| I114N | 21 | |||||
| Between loop II and loop III (115-151) | ||||||
| G115V* | Decreased | 57 | ||||
| C117R | Decreased | 43 | ||||
| C117W | 25 | |||||
| C128R | 21 | |||||
| W139S* | 47 | |||||
| C145S* | This study | |||||
| Loop III (152-163) | ||||||
| N152K* | 58 | |||||
| H154R | 59 | |||||
| M157V* | Decreased | N.C. | N.C. | 44 | ||
| M157T* | 60 | |||||
| M157K | 54 | |||||
| E160Q | 21 | |||||
| E160K* | This study | |||||
| G161R* | 47 | |||||
| Linker (164-203) | ||||||
| P168S | 49 | |||||
| E180K* | Decreased | N.C. | 40 | |||
| C181R | Affected | 29 | ||||
| C181Y | 29 | |||||
| TM1 and ICL1 (204-249) | ||||||
| C204R* | Decreased | Affected | Affected | 29 | ||
| C204Y | Affected | 29 | ||||
| C204F | 61 | |||||
| Y211H | Decreased | N.C. | 62 | |||
| M223K* | 63 | |||||
| W226R* | 60 | |||||
| S228R* | 41 | |||||
| L229P | 64 | |||||
| I232V* | 41 | |||||
| T234I* | 21 | |||||
| T237R* | Decreased | N.C. | 30 | |||
| L239P* | 65 | |||||
| S245T* | 41 | |||||
| TM2 and ECL1 (250-299) | ||||||
| Y250C* | 66 | |||||
| R253H* | Decreased | N.C. | Affected | 30 | ||
| L273R | 67 | |||||
| I293V | 41 | |||||
| K298E | 68 | |||||
| TM3 and ICL2 (300-336) | ||||||
| C302Y | Decreased | 69 | ||||
| I322F | 70 | |||||
| L325R | 25 | |||||
| F328S | Decreased | N.C. | Affected | 30 | ||
| W335C* | N.C. | 29 | ||||
| TM4 and ECL2 (337-383) | ||||||
| A339T | 48 | |||||
| M342V* | 71 | |||||
| S344R | 41 | |||||
| S344T | 41 | |||||
| F347V | N.C. | 72 | ||||
| H348Q | 58 | |||||
| K358N | 43 | |||||
| C377F* | This study | |||||
| TM5 and ICL3 (384-431) | ||||||
| P394L | 25 | |||||
| R417Q* | Decreased | N.C. | N.C. | 73 | ||
| L420I | 59 | |||||
| TM6 and ECL3 (432-473) | ||||||
| M434V | 41 | |||||
| I437T | Decreased | 57 | ||||
| V442E | Decreased | 69 | ||||
| L443P | 64 | |||||
| T445P* | N.C. | 29 | ||||
| D470N | N.C. | N.C. | 48 | |||
| TM7 (474-495) | ||||||
| G488D* | Affected | 29 | ||||
| G488V | 54 | |||||
| G492R* | N.C. | 29 | ||||
| ICD (496-537) | ||||||
| S497F* | 16 | |||||
| L501P | 41 | |||||
| G525R | 50 | |||||
| G530E | 43 |
ICL, intracellular loop; ECL, extracellular loop; ICD, intracellular domain; N.C., no change.
*
The mutations investigated in this study.