Table 1.
Congenital pigmentation disorders with cloned and characterized genetic components.1
| Disease | Gene | Encoded Protein Function |
|---|---|---|
| Piebaldism | KIT | Receptor tyrosine kinase; ligand is KITLG |
| SNAI2 | Transcription factor | |
| Waardenburg syndrome 1 | PAX3 | Transcription factor |
| Waardenburg syndrome 2 | MITF | Transcription factor |
| SOX10 | Transcription factor | |
| SNAI2 | Transcription factor | |
| Waardenburg syndrome 3 | PAX3 | Transcription factor |
| Waardenburg syndrome 4 | SOX10 | Transcription factor |
| EDNRB | Transmembrane receptor; ligand is EDN3 | |
| EDN3 | Secreted growth factor | |
| Peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and hirschsprung disease | SOX10 | Transcription factor |
| Tietz syndrome | MITF | Transcription factor |
| Yemenite deaf-blind hypopigmentation syndrome | SOX10 | Transcription factor |
| Albinism, black lock, cell migration disorder of the neurocytes of the gut, and deafness syndrome | EDNRB | Transmembrane receptor; ligand is EDN3 |
| Oculocutaneous albinism 1 | TYR | Melanogenic, rate-limiting enzyme |
| Oculocutaneous albinism 2 | OCA2 | Melanosome membrane protein |
| Oculocutaneous albinism 3 | TYRP1 | Melanogenic enzyme |
| Oculocutaneous albinism 4 | SLC45A2 | Solute transporter |
| Hermansky-Pudlak syndrome | HPS1 | Member of BLOC-3 complex; regulates lysosome-related organelle movement |
| AP3B1 | Member of AP3 complex; regulates protein sorting | |
| HPS3 | Member of BLOC-2 complex; regulates lysosome-related organelle movement | |
| HPS4 | Member of BLOC-3 complex; regulates lysosome-related organelle movement | |
| HPS5 | Member of BLOC-2 complex; regulates lysosome-related organelle movement | |
| HPS6 | Member of BLOC-2 complex; regulates lysosome-related organelle movement | |
| DTNBP1 | Member of BLOC-1 complex; regulates lysosome-related organelle movement | |
| BLOC1S3 | Member of BLOC-1 complex; regulates lysosome-related organelle movement | |
| PLDN | Member of BLOC-1 complex; regulates lysosome-related organelle movement | |
| Chediak-Higashi syndrome | LYST | Function unknown; may regulate lysosome-related organelle size and trafficking |
| Griscelli syndrome | MYO5A | Myosin motor regulating melanosome transport |
| RAB27A | RAS-associated protein that interacts with MLPH to regulate melanosome transport | |
| MLPH | Interacts with MYO5A to regulate melanosome transport | |
| LEOPARD syndrome | PTPN11 | MAPK signal transduction pathway |
| RAF1 | MAPK signal transduction pathway | |
| BRAF | MAPK signal transduction pathway | |
| Noonan syndrome | PTPN11 | Cytoplasmic protein tyrosine phosphatase; modulates RAS activity |
| RAF1 | Serine threonine kinase; downstream effector of RAS | |
| BRAF | Serine threonine kinase; downstream effector of RAS | |
| SHOC2 | Leucine-rich protein; modulates RAS activity | |
| KRAS | Monomeric GTPase; modulates RAS activity | |
| SOS1 | Guanine nucleotide exchange factor; modulates RAS activity | |
| NRAS | Monomeric GTPase; modulates RAS activity | |
| Cardio-facio-cutaneous syndrome | KRAS | Monomeric GTPase; modulates RAS activity |
| BRAF | Serine threonine kinase; downstream effector of RAS | |
| MAP2K1 | Dual specificity kinase; acts downstream of RAS as RAF effector | |
| MAP2K2 | Dual specificity kinase; acts downstream of RAS as RAF effector | |
| CBL-mutation associated syndrome | CBL | E3 ubiquitin ligase; acts downstream of receptor tyrosine kinases |
| Legius syndrome | SPRED1 | Sprouty domain protein; tyrosine kinase substrate; modulates RAS activity |
| Dyschromatosis symmetrica hereditaria | ADAR | RNA specific adenosine deaminase; regulates RNA editing |
| GIST with dysplastic nevi and lentigines | KIT | Receptor tyrosine kinase; ligand is KITLG |
| Peutz-Jeghers syndrome | STK11 | Serine threonine kinase |
| Carney complex | PRKAR1A | Protein kinase regulatory subunit |
| Neurofibromatosis | NF1 | RAS GTPase, modulates RAS activity |
| Neurofibromatosis-Noonan syndrome | NF1 | RAS GTPase, modulates RAS activity |
| Familial progressive hyperpigmentation 2 | KITLG | Growth factor; ligand for KIT |
| Familial progressive hyper- and hypopigmentation | KITLG | Growth factor; ligand for KIT |
| Fanconi anemia | Heterogeneous see OMIM #227650 | Associated with mutation of at least 15 loci, which encode proteins that regulate various DNA repair processes |
1
This table is not an exhaustive list of all known congenital pigmentation disorders. For extensive descriptions of published human pigmentation disorders, see Further Reading/Resources.