Table 1.
List of human mutations found in homeodomains and their associated diseases.Abbreviations used in the ‘Mutational effects’ DB disruption of DNA binding, NL disruption of nuclear localization, PS disruption of protein stability, DI disruption of domain-domain interactions, ? not explainable from the structure). The references for each mutation can be found in the databases available online, especially in Online Mendelian Inheri-column: tance in Man in Baltimore (http://www.ncbi.nlm.nih.gov/omim) ( and the Bioinformatic Harvester in Heidelberg (http://harvester.embl.de)
| Disease/syndrome | Gene product | OMIM number (gene) | Homeobox class | Missense mutation | Mutational effects |
|---|---|---|---|---|---|
| Parietal foramina | ALX4 | 605420 | Homeodomain (214-273) | R218Q | DB/NL |
| R272P | PS | ||||
| Infantile spasm syndrome | ARX | 300382 | Homeodomain (328-387) | R332H | DB |
| L343Q | PS | ||||
| P353L | PS | ||||
| Microphthalmia | CHX10 | 142993 | Homeodomain (148-207) | R200P | DB |
| R200Q | DB | ||||
| Cone-rod dystrophy | CRX | 602225 | Homeodomain (39-98) | R41Q | NL |
| R41W | NL | ||||
| E80A | ? | ||||
| R90W | PS/DB | ||||
| Septooptic dysplasia | HESX1 | 601802 | Homeodomain (108-167) | N125S | PS(?) |
| R160C | DB | ||||
| Currarino syndrome | HLXB9 | 142994 | Homeodomain (242-301) | R246G | DB/NL |
| R246H | DB/NL | ||||
| T247S | PS | ||||
| W289G | PS | ||||
| W289L | PS | ||||
| Q291P | PS/DB | ||||
| R293W | PS/DB | ||||
| R294Q | DB | ||||
| R294W | DB | ||||
| Hand-foot genital syndrome | HOXA13 | 142959 | Homeodomain (322-381) | Q371L | PS |
| N372H | DB | ||||
| Synpolydactyly | HOXD13 | 142989 | Homeodomain (268-327) | S308C | PS |
| I314L | PS/DB | ||||
| MODY4 (diabetes) | IPF-1/PDX-1 | 600733 | Homeodomain (146-205) | R197H | PS/DB |
| Hypodontia | MSX1 | 142983 | Homeodomain (166-225) | R196P | PS/DB |
| Parietal foramina craniosynostosis | MSX2 | 123101 | Homeodomain (142-201) | P148H | PS |
| L154P | PS | ||||
| R172H | PS/DB | ||||
| R194S | DB | ||||
| Atrila septal defect | NKX2.5 (CSX) | 600584 | Homeodomain (138-197) | T178M | PS |
| Q187H | PS/DB | ||||
| N188K | DB | ||||
| R189G | PS/DB | ||||
| Y191C | DB | ||||
| Rieger syndrome | PITX2 | 601542 | Homeodomain (85-144) | R43W | DB/NL |
| L54Q | PS | ||||
| T68P | PS | ||||
| R69H | PS/DB | ||||
| V83L | PS | ||||
| R84W | DB | ||||
| K88E | PS/DB | ||||
| R90C | PS/DB | ||||
| R91P | DB | ||||
| Leri-Weill dyschondrosteosis | SHOX | 312865 | Homeodomain (117-176) | Q128L | PS |
| L132V | PS | ||||
| Langer mesomelic dysplasia | R153L | PS(?) | |||
| R153S | PS(?) | ||||
| L154P | PS | ||||
| V163F | PS/DB | ||||
| R168W | PS/DB | ||||
| A170P | PS/DB | ||||
| R173H | PS | ||||
| R173C | PS | ||||
| Holoprosencephaly | SIX3 | 603714 | Homeodomain (206-266) | L226V | PS(?) |
| V250A | PS | ||||
| R257P | PS/DB | ||||
| Holoprosencephaly | TGIF | 602630 | Homeodomain (35-97) | P63R | PS/DB |
| R90C | DB | ||||
| Keratoconus | VSX1 | 605020 | Homeodomain (164-223) | R166W | NL |
| Waardenburg syndrome | PAX3 | 606597 | Paired box-homeodomain (219-278) | F238S | PS/DB |
| 193500 | V265F | PS/DB | |||
| W266C | PS | ||||
| R270C | PS/DB | ||||
| R271G | DB | ||||
| R271H | DB | ||||
| Coloboma of optic nerve | PAX6 | 607108 | Pairedbox-homeodomain (210-269) | F258S | PS |
| Neuroblastoma | PHOX2B | 603815 | Paired-like homeodomain (98-157) | R100L | NL |
| R141G | DB | ||||
| Pituitary hormone deficiency | PROP-1 | 601538 | Paired-like homeodomain (69-128) | R73H | DB/NL |
| R73C | DB/NL | ||||
| F88S | PS/DB | ||||
| F117I | PS | ||||
| R120C | PS/DB | ||||
| Nail-patella syndrome | LMX1B | 602575 | LIM-homeodomain (196-255) | R200Q | DB/NL |
| 161200 | A213P | PS(?) | |||
| S218P | PS(?) | ||||
| R226P | PS/DB | ||||
| L229P | PS | ||||
| A230V | PS | ||||
| W243C | PS | ||||
| N246K | DB | ||||
| A249P | PS/DB | ||||
| Pituitary hormone deficiency | PIT-1/POU1F1 | 173110 | POU-homeodomain (214-273) | K216E | NL |
| D227Y | ? | ||||
| E230K | PS | ||||
| P239S | PS/DB | ||||
| R265W | PS/DB | ||||
| R271W | DI | ||||
| Deafness | POU3F4 | 300039 | POU-homeodomain (278-337) | A312V | PS |
| L317W | PS | ||||
| R323G | DB | ||||
| R330S | DB | ||||
| K334E | PS/DI | ||||
| Diabetes ( MODY5) | HNF1b (TCF-2) | 604284 | POU-homeodomain (231-311) | A241T | PS |
| Diabetes ( MODY3) | HNF1a | 142410 | POU-homeodomain (199-279) | R200W | NL |
| R200Q | NL | ||||
| R203C | DB/NL | ||||
| R203H | DB/NL | ||||
| K205 | DB/DI | ||||
| Y218C | PS/DB | ||||
| R229Q | PS/DB | ||||
| R229P | PS/DB | ||||
| E240Q | PS/DI | ||||
| E240H | PS/DI | ||||
| C241G | PS/DI | ||||
| C241 | PS/DI | ||||
| L254M | DI | ||||
| S256T | DI | ||||
| V259D | PS | ||||
| V259G | PS | ||||
| T260M | PS/DB | ||||
| R263C | DB | ||||
| R271W | PS/DB | ||||
| R271G | PS/DB | ||||
| R272H | DB | ||||
| R272C | DB |