Table 3:
Osteopetrosis.
| Type | OMIM | Defective gene | Protein | OMIM | Locus | Inheritance, associated features |
|---|---|---|---|---|---|---|
| Osteoclast differentiation | ||||||
| AR2 | 259710 | TNFSF11 | Tumor necrosis factor ligand superfamily, member 11 | 602642 | 13q14.11 | AR, receptor activator of NFkB – ligand (RANKL) |
| AR7 | 612301 | TNFRSF11A | Tumor necrosis factor receptor superfamily, member 11A | 603499 | 18q21.33 | AR, receptor activator of NFkB – (RANK) |
| AD1 | 607634 | LRP5 | Low density lipoprotein-receptor-related protein 5 | 603506 | 11 q13.2 | AD, transduces WNT signaling enabling osteoclastogenesis |
| NA | 300248 | IKBKG | IKBKG Inhibitor of nuclear factor kappa-B kinase, Regulatory subunit gamma | 300248 | Xq28 | XLR, enables NFkB- mediated osteoclast differentiation, associated with ectodermal dysplasia |
| NA | IGSF23 | Immunoglobulin superfamily member 23 | NA | 19q13.31 | AR, receptor promoting M-CSF and RANK ligand – mediated differentiation of osteoclasts by activating MAPK signaling | |
| NA | 617306 | MITF | Microphthalmia -associated transcription factor | 156845 | 3p13 | AR, developmental protein, variant associated with syndrome of coloboma, osteopetrosis, microphthalmia, albinism |
| Osteoclast function | ||||||
| NA | FERMT3 | Fermitin family, member 3 | 607901 | 11q13.1 | AR. transmembrane adhesion receptor facilitating cell-to-cell-to-extracellular matrix protein interaction | |
| NA | ITGB3 | Integrin, beta 3 | 173470 | 17q21.32 | AR, transmembrane adhesion receptor that facilitates cell-to-cell-to-extracellular matrix protein interaction | |
| AR22 | CCDC134 | Coil-coiled domain-containing protein 134 | 618788 | 22q13 | AR, regulator of transcription, signal transduction | |
| Synthesis of hydrochloric acid | ||||||
| AR3 | 259730 | CA2 | Carbonic anhydrase II | 611492 | 8q21.2 | AR, catalyzes dissociation of carbonic acid, associated with renal tubular acidosis |
| Acid transport/secretion/mineral dissolution | ||||||
| AR8 | 615085 | SNX10 | Sorting nexin 10 | 614780 | 7p15.2 | AR, necessary for vacuole formation and trafficking severe neonatal form |
| AR6 | 611497 | PLEKHM1 | Pleckstrin homology domain containing protein,family M, member 1 | 611466 | 17q21.31 | AR/AD, enables vesicular transport in osteoclasts, intermediate severity |
| AD3 | 618107 | PLEKHM1 | ||||
| AR4 | 611490 | CLCN7 | Chloride channel 7 | 602727 | 16p13.3 | AR/AD, chloride channel that interacts with OSTM1, variable severity |
| AD2 | 166600 | CLCN7 | ||||
| AR5 | 259720 | OSTM1 | Osteopetrosis-associated transmembrane protein1 | 607649 | 6q21 | AR, forms stable molecular complex with CLCN7, infantile form with involvement of nervous system |
| AR1 | 259700 | TCIRG1 | T Cell immune regulator 1 | 604592 | 11 q13.2 | AR, osteoclast proton pump, severe neonatal form |
| Other | ||||||
| Pycknodysostosis | 265800 | CTSK | Cathepsin K | 601105 | 1q21.3 | AR, cysteine proteinase that degrades bone collagen matrix; bone fragility despite osteosclerosis |
| Sclerosteosis 1 | 269500 | SOST | Sclerostin | 605740 | 17q21.31 | AR, bone morphogenic protein antagonist secreted by osteocytes; interacts with LRP5, LRP6 |
NA, not assigned; AD, autosomal dominant; AR, autosomal recessive; XLR, X-linked recessive.