Table 2.
Overview of functional testing results of FBXO11 missense variants
| Varianta | Domainb | Modelling | Complex formation | Localization | Expression level | Variant reported | |
|---|---|---|---|---|---|---|---|
| WT | N + C | 100 | |||||
| K135R (K51R) | NLS | Np | Nd | C | 47 ± 14 | 0.03 | This study |
| R138G (R54G) | NLS | Np | Normal | C | 60 ± 10 | 0.02 | This study |
| R138S (R54S) | NLS | Np | Normal | C | 53 ± 14 | 0.03 | (2) |
| Q156R (Q72R) | F-Box | Np | Normal | Granula | 49 ± 13 | 0.03 | (2) |
| F168del (F84del) | F-Box | Loss of stabilizing interaction | Nd | Granula | 69 ± 7 | 0.02 | This study |
| R185H (R101H) | F-Box | Loss of stabilizing interaction | Nd | Granula | 55 ± 14 | 0.04 | This study |
| Y206C (Y122C) | Np | Nd | N + C | 43 ± 8 | 0.004 | This study | |
| G421R (G337R) | CASH 1 | Steric clashes | Nd | N + C | 55 ± 9 | 0.009 | This study |
| T502P (T418P) | CASH 1 | Nd | Nd | Nd | Nd | Nd | This study |
| Y506C (Y422C) | CASH 1 | Loss of stabilizing interaction | Normal | Granula | 59 ± 12 | 0.03 | (3) |
| I538V (I454V) | CASH 1 | Loss of stabilizing interactionc | Normal | Granula | 98 ± 6 | 0.8 | (2) |
| G549R (G465R) | CASH 1 | Steric clashes | Nd | Granula | 47 ± 10 | 0.01 | This study |
| G550R (G466R) | CASH 1 | Nd | Nd | Nd | Nd | Nd | This study |
| T578R (T494R) | CASH 2 | Nd | Nd | Nd | Nd | Nd | This study |
| T623R (T539R) | CASH 2 | Electrostatic repulsionc | Normal | Granula | 106 ± 12 | 0.7 | (2) |
| H650P (H566P) | CASH2 | Destabilization of domain structure | Nd | Nd | Nd | Nd | This study |
| N679S (N595S) | CASH 2 | Loss of stabilizing interaction | Nd | N + C | 57 ± 6 | 0.005 | This study |
| M709V (M625V) | CASH 3 | Np | Nd | Nd | Nd | Nd | This study |
| S840P (S756P) | Zf-UBR | Steric clashesc | Normal | Granula, coloc. With SCF | 116 ± 27 | 0.6 | (2) |
| A892D (A808D) | Zf-UBR | Conformational changec | Normal | Granula | 120 ± 21 | 0.4 | (2) |
| P905R (P821R) | Np | Normal | N + C | 95 ± 30 | 0.9 | (2) | |
| D910G (D826G) | Np | Normal | Granula | 118 ± 21 | 0.4 | (2) | |
| D910V (D826V) | Np | Nd | Nd | Nd | Nd | This study | |
Nd: not determined, Np: not possible, N: nuclear, C: cytoplasmic.
a
Annotation according to the longest isoform NP_001177203.1 (and shorter cloned isoform NP_079409.3).
b
Domain structure according to Interpro.
c
Reported in Gregor et al. (2).