ANKH transports PPi from cytosol to extracellular region

Stable Identifier
Reaction [transition]
Homo sapiens
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Progressive ankylosis protein homolog (ANKH) is a putative transmembrane pyrophosphate (PPi) transport channel protein found in osteoblasts of various bones. It mediates the transport of cytosolic PPi to the extracellular matrix. Abnormal transport of PPi is implicated in familial calcium pyrophosphate dihydrate deposition (CPPD) disease. There are two forms of CPPD disease: CCAL1 and CCAL2. Defects in ANKH can cause chondrocalcinosis (CCAL2; MIM:118600), a chronic condition in which PPi crystals deposit in the joint fluid, cartilage, and periarticular tissues and there is calcium deposition in articular cartilage (Pendleton et al. 2002, Williams et al. 2002, Williams et al. 2003). Defects in ANKH can also cause craniometaphyseal dysplasia, autosomal dominant (CMDD; MIM:123000), an osteochondrodysplasia characterised by progressive thickening and increased mineral density of craniofacial bones and abnormal modelling of metaphyses in long bones (Nurnberg et al. 2001, Reichenberger et al. 2001).
Literature References
PubMed ID Title Journal Year
11326272 Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia

Chandler, D, Mundlos, S, Harrop, K, Nürnberg, P, Westermann, F, Goldblatt, J, Ritter, H, Braun, HS, Laing, N, Borochowitz, ZU, Cunningham, ML, Mischung, C, Leschik, G, Tinschert, S, Kotzot, D, Uhlmann, K, Höhne, W, Thiele, H

Nat. Genet. 2001
13130483 Mutations in the amino terminus of ANKH in two US families with calcium pyrophosphate dihydrate crystal deposition disease

Williams, CJ, Doherty, M, McCarty, DJ, Peariso, S, Reginato, AJ, Pendleton, A, Ryan, LM, Bonavita, G, Hughes, AE

Arthritis Rheum. 2003
11326338 Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK

Beighton, P, Grange, DK, Sommer, A, Sellars, S, Raposo do Amaral, CM, Hamersma, H, Ueki, Y, Ramesar, R, Park, L, Tiziani, V, Reichenberger, E, Santanna, C, Watanabe, S, Olsen, BR, Gorlin, RJ, Shiang, R, Lidral, AC, Mulliken, JB, Baur, ST, Gardner, J

Am. J. Hum. Genet. 2001
12297989 Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH

Russell, RG, Williams, CJ, Cuthbertson, J, Timms, A, Brown, MA, Wordsworth, BP, Jones, Y, Broxholme, J, Bonavita, G, Caeiro, F, Zhang, Y, Carr, AJ, Marchegiani, R, Reginato, A

Am. J. Hum. Genet. 2002
12297987 Mutations in ANKH cause chondrocalcinosis

Netter, P, Ho, AM, Hughes, A, Kingsley, DM, Dixey, J, Loeuille, D, Gurley, KA, Doherty, M, Johnson, MD, Williams, C, Wright, G, Shiang, R, Pendleton, A, McGrath, R, Reginato, A, Gillet, P

Am. J. Hum. Genet. 2002
Catalyst Activity

inorganic diphosphate transmembrane transporter activity of ANKH [plasma membrane]

Orthologous Events
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