Reviewed February 2009
What is the official name of the ANKH gene?
The official name of this gene is “ANKH inorganic pyrophosphate transport regulator.”
ANKH is the gene's official symbol. The ANKH gene is also known by other names, listed below.
What is the normal function of the ANKH gene?
The ANKH gene provides instructions for making a protein that is present in bone. This protein transports a molecule called pyrophosphate out of cells to the intricate network of proteins that forms in the spaces between cells (extracellular matrix). Pyrophosphate helps regulate bone formation by preventing mineralization, the process by which minerals such as calcium and phosphorus are deposited in developing bones. The ANKH protein may have other, unknown functions.
How are changes in the ANKH gene related to health conditions?
- craniometaphyseal dysplasia - caused by mutations in the ANKH gene
At least seven mutations in the ANKH gene have been found to cause craniometaphyseal dysplasia. Some mutations change a single protein building block (amino acid) in the ANKH protein, whereas others insert or delete an amino acid in the ANKH protein. These mutations most likely decrease the protein's ability to transport pyrophosphate out of cells. Reduced levels of pyrophosphate increase bone mineralization, which may contribute to the bone overgrowth seen in craniometaphyseal dysplasia.
- other disorders - associated with the ANKH gene
About five mutations in the ANKH gene have been found to cause a rare hereditary form of calcium pyrophosphate dihydrate deposition disease (CPPDD). CPPDD, also called chondrocalcinosis or pseudogout, is characterized by the accumulation of calcium pyrophosphate dihydrate crystals in the cartilage of joints. The buildup of these crystals weakens cartilage and causes it to break down more easily. The crystals may cause pain and inflammation in the joints. Most cases of CPPDD occur in people older than 40, are not inherited, and have an unknown cause.
Mutations in the ANKH gene have been shown to cause CPPDD in a few families. In these families, one altered copy of the ANKH gene in each cell is sufficient to cause the condition. Individuals with familial CPPDD caused by ANKH mutations typically form crystal deposits within multiple joints during early adulthood. Researchers believe that these mutations lead to elevated pyrophosphate levels in the extracellular matrix. High levels of pyrophosphate result in excessive formation of calcium pyrophosphate dihydrate crystals within joints.
Studies suggest that certain variations (polymorphisms) in the ANKH gene are associated with the normal difference in bone size and shape among individuals. These polymorphisms probably result in slight changes in the activity of the ANKH protein, affecting the levels of pyrophosphate in the extracellular matrix.
Where is the ANKH gene located?
Cytogenetic Location: 5p15.1
Molecular Location on chromosome 5: base pairs 14,704,800 to 14,871,778
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/56172))
The ANKH gene is located on the short (p) arm of chromosome 5 at position 15.1.
More precisely, the ANKH gene is located from base pair 14,704,800 to base pair 14,871,778 on chromosome 5.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about ANKH?
You and your healthcare professional may find the following resources about ANKH helpful.
Educational resources - Information pages
- Merck Manual Professional Version: Calcium Pyrophosphate Dihydrate Deposition Disease (http://www.merckmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/crystal-induced-arthritides/calcium-pyrophosphate-dihydrate-crystal-deposition-disease)
- Molecular Biology of the Cell (fourth edition, 2002): Bone Is Continually Remodeled by the Cells Within It (http://www.ncbi.nlm.nih.gov/books/NBK26889/)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1461)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for ANKH (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=56172%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28ANKH%5BTIAB%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- ANK, MOUSE, HOMOLOG OF (http://omim.org/entry/605145)
- CHONDROCALCINOSIS 2 (http://omim.org/entry/118600)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_ANKH.html)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=15492)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/56172)
What other names do people use for the ANKH gene or gene products?
- ankylosis, progressive homolog (mouse)
- progressive ankylosis protein
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding ANKH?
amino acid ;
bone formation ;
bone mineralization ;
extracellular matrix ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Addison WN, Azari F, Sørensen ES, Kaartinen MT, McKee MD. Pyrophosphate inhibits mineralization of osteoblast cultures by binding to mineral, up-regulating osteopontin, and inhibiting alkaline phosphatase activity. J Biol Chem. 2007 May 25;282(21):15872-83. Epub 2007 Mar 23. (http://www.ncbi.nlm.nih.gov/pubmed/17383965?dopt=Abstract)
- Gene Review: Craniometaphyseal Dysplasia, Autosomal Dominant (http://www.ncbi.nlm.nih.gov/books/NBK1461)
- 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. Epub 2006 Oct 16. (http://www.ncbi.nlm.nih.gov/pubmed/17186460?dopt=Abstract)
- Korostishevsky M, Vistoropsky Y, Malkin I, Kobyliansky E, Livshits G. Anthropometric and bone-related biochemical factors are associated with different haplotypes of ANKH locus. Ann Hum Biol. 2008 Sep-Oct;35(5):535-46. doi: 10.1080/03014460802304588. (http://www.ncbi.nlm.nih.gov/pubmed/18821330?dopt=Abstract)
- Malkin I, Dahm S, Suk A, Kobyliansky E, Toliat M, Ruf N, Livshits G, Nürnberg P. Association of ANKH gene polymorphisms with radiographic hand bone size and geometry in a Chuvasha population. Bone. 2005 Feb;36(2):365-73. (http://www.ncbi.nlm.nih.gov/pubmed/15780964?dopt=Abstract)
- Malkin I, Ermakov S, Kobyliansky E, Livshits G. Strong association between polymorphisms in ANKH locus and skeletal size traits. Hum Genet. 2006 Aug;120(1):42-51. Epub 2006 Apr 26. (http://www.ncbi.nlm.nih.gov/pubmed/16724232?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/56172)
- Nürnberg P, Thiele H, Chandler D, Höhne W, Cunningham ML, Ritter H, Leschik G, Uhlmann K, Mischung C, Harrop K, Goldblatt J, Borochowitz ZU, Kotzot D, Westermann F, Mundlos S, Braun HS, Laing N, Tinschert S. Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia. Nat Genet. 2001 May;28(1):37-41. (http://www.ncbi.nlm.nih.gov/pubmed/11326272?dopt=Abstract)
- Pendleton A, Johnson MD, Hughes A, Gurley KA, Ho AM, Doherty M, Dixey J, Gillet P, Loeuille D, McGrath R, Reginato A, Shiang R, Wright G, Netter P, Williams C, Kingsley DM. Mutations in ANKH cause chondrocalcinosis. Am J Hum Genet. 2002 Oct;71(4):933-40. Epub 2002 Sep 20. (http://www.ncbi.nlm.nih.gov/pubmed/12297987?dopt=Abstract)
- Reichenberger E, Tiziani V, Watanabe S, Park L, Ueki Y, Santanna C, Baur ST, Shiang R, Grange DK, Beighton P, Gardner J, Hamersma H, Sellars S, Ramesar R, Lidral AC, Sommer A, Raposo do Amaral CM, Gorlin RJ, Mulliken JB, Olsen BR. Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK. Am J Hum Genet. 2001 Jun;68(6):1321-6. Epub 2001 Apr 16. (http://www.ncbi.nlm.nih.gov/pubmed/11326338?dopt=Abstract)
- Tsui HW, Inman RD, Paterson AD, Reveille JD, Tsui FW. ANKH variants associated with ankylosing spondylitis: gender differences. Arthritis Res Ther. 2005;7(3):R513-25. Epub 2005 Feb 25. (http://www.ncbi.nlm.nih.gov/pubmed/15899038?dopt=Abstract)
- Zaka R, Williams CJ. Genetics of chondrocalcinosis. Osteoarthritis Cartilage. 2005 Sep;13(9):745-50. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15951203?dopt=Abstract)
- Zaka R, Williams CJ. Role of the progressive ankylosis gene in cartilage mineralization. Curr Opin Rheumatol. 2006 Mar;18(2):181-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16462526?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.