Table 6.
List of THR-like receptor LBD mutations associated with diseases in humans.
| S. No. | Receptor | Mutation | Classification | Alignment Position | Disease-Associated |
|---|---|---|---|---|---|
| 1 | THRα | N359Y | Function | 484 | in CHNG6; atypical phenotype; weak reduction in transcriptional activation |
| 2 | THRα | A263S | Function | 258 | in CHNG6; no effect on T3 binding; no effect on thyroid hormone-dependent transcriptional activation |
| 3 | THRβ | R429Q/W | Fold | 506 | in PRTH |
| 4 | THRβ | S350L | Function | 368 | in GRTHD |
| 5 | THRβ | V349M | Fold | 367 | in GRTHD |
| 6 | THRβ | V348E | Function | 366 | in GRTHD |
| 7 | THRβ | G347E/A | Fold | 364 | in GRTHD |
| 8 | THRβ | L346F | Fold/Function | 363 | in GRTHD |
| 9 | THRβ | G345R/V/S | Fold | 361 | in GRTHD |
| 10 | THRβ | G344E/A | Function | 360 | in GRTHD |
| 11 | THRβ | K342I | Function | 343 | in GRTHD |
| 12 | THRβ | L341P | Function | 336 | in GRTHD |
| 13 | THRβ | Q340H | Function | 335 | in GRTHD |
| 14 | THRβ | R338W/L | Fold | 295 | in GRTHD |
| 15 | THRβ | Del337T | Function | 294 | in GRTHD |
| 16 | THRβ | A335P | Function | 292 | in GRTHD |
| 17 | THRβ | E333D | Fold | 277 | in GRTHD |
| 18 | THRβ | G332R/E | Function | 276 | in GRTHD |
| 19 | THRβ | N331D | Function | 275 | in GRTHD |
| 20 | THRβ | L330S | Fold | 273 | in GRTHD |
| 21 | THRβ | T329I | Function | 272 | in GRTHD |
| 22 | THRβ | T327A | Function | 269 | in GRTHD |
| 23 | THRβ | Y321C/H | Fold | 262 | in GRTHD |
| 24 | THRβ | R320H/G | Function | 261 | in GRTHD |
| 25 | THRβ | A317T/S | Function | 258 | in GRTHD; impairs hormone binding |
| 26 | THRβ | R316H/C | Fold | 257 | in PRTH; impairs hormone binding |
| 27 | THRβ | A268G | Function | 207 | in GRTHD |
| 28 | THRβ | R243W | Fold | 80 | in GRTHD |
| 29 | THRβ | A234T | Function | 71 | in GRTHD; impairs hormone binding and ligand-dependent conformational changes |
| 30 | RARβ | R394C | Function | 523 | in MCOPS12; increased transcriptional response to retinoic acid ligands |
| 31 | RARβ | R394S | Function | 523 | in MCOPS12; increases transcriptional response to retinoic acid |
| 32 | RARβ | G303A | Fold | 361 | in MCOPS12; Increased transcriptional response to retinoic acid ligands |
| 33 | RARβ | L220P | Function | 204 | in MCOPS12; Increased transcriptional response to retinoic acid ligands |
| 34 | VDR | R391C | Fold | 506 | in VDDR2A |
| 35 | VDR | S360P | Function | 456 | in VDDR2A; loss of calcitriol receptor activity; loss of affinity for calcitriol; decreased ligand-independent localization to the nucleus; loss of interaction with RXRA; loss of interaction with NCOR1; loss of interaction with NCOA1; loss of sequence-specific DNA binding. |
| 36 | VDR | V346M | Fold | 422 | in VDDR2A; decreased calcitriol receptor activity; decreased affinity for calcitriol; decreased ligand-independent localization to the nucleus; loss of interaction with RXRA; decreased interaction with NCOR1; decreased interaction with NCOA1; decreased sequence-specific DNA-binding. |
| 37 | VDR | I314S | Fold | 372 | in VDDR2A |
| 38 | VDR | H305Q | Fold/Function | 363 | in VDDR2A; loss of calcitriol receptor activity; no effect on interaction with RXRA; changed interaction with NCOR1; loss of interaction with NCOA1; no effect on sequence-specific DNA binding. |
| 39 | VDR | R274L/H | Fold | 257 | in VDDR2A; loss of calcitriol receptor activity; decreased affinity for calcitriol by a factor of 1000; no effect on interaction with RXRA; changed interaction with NCOR1; loss of interaction with NCOA1; no effect on sequence-specific DNA binding. |
| 40 | PPARγ | P495L | Fold | 542 | in Diabetes |
| 41 | PPARγ | R425C | Fold | 418 | in FPLD3 |
| 42 | PPARγ | F388L | Fold/Function | 363 | in FPLD3 |
| 43 | PPARγ | V318M | Fold | 216 | in diabetes |
| 44 | PPARγ | R316H | Function | 214 | in colon cancer; sporadic; somatic mutation; partial loss of ligand-binding |
| 45 | PPARγ | Q314P | Function | 212 | in colon cancer; sporadic; somatic mutation; loss of ligand-binding |
| 46 | RORα | R462Q | Function | 481 | in IDDECA; loss of function in cerebellar development, when assayed in a heterologous system |
| 47 | RORα | S409R | Function | 379 | in IDDECA |