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ANKH

MIM.605145 5p15.2-p14.1

ANKH encodes a putative transmembrane inorganic pyrophosphate (PPi) transport channel. It is a multiple-pass transmembrane protein that regulates pyrophosphate levels inside and outside tissue culture cells in vitro.

Pathology

Mutations in the progressive ankylosis gene (Ank/ANKH) cause surprisingly different skeletal phenotypes in mice and humans.

In humans, some dominant mutations cause chondrocalcinosis, an adult-onset disease characterized by the deposition of ectopic joint crystals.

Other dominant mutations cause craniometaphyseal dysplasia, a childhood disease characterized by sclerosis of the skull and abnormal modeling of the long bones, with little or no joint pathology.

- mutations in the familial autosomal dominant calcium pyrophosphate dihydrate chondrocalcinosis (#12297989#, #12297987#)

Animal model

Mutation at the mouse ’progressive ankylosis’ (ank) locus causes a generalized, progressive form of arthritis accompanied by mineral deposition, formation of bony outgrowths, and joint destruction.

In mice, recessive loss-of-function mutations cause arthritis, ectopic crystal formation, and joint fusion throughout the body.

References

- Gurley KA, Reimer RJ, Kingsley DM. Biochemical and genetic analysis of ANK in arthritis and bone disease. Am J Hum Genet. 2006 Dec;79(6):1017-29. PMID: #17186460#