Alkaline phosphatase, tissue-nonspecific isozyme is an enzyme that in humans is encoded by the ALPLgene.
There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue-nonspecific). The first three are located together on chromosome 2, whereas the tissue-nonspecific form is located on chromosome 1. The product of this gene is a membrane-bound glycosylated enzyme that is not expressed in any particular tissue and is, therefore, referred to as the tissue-nonspecific form of the enzyme. The exact physiological function of the alkaline phosphatases is not known. A proposed function of this form of the enzyme is matrix mineralization. However, mice that lack a functional form of this enzyme show normal skeletal development. This enzyme has been linked directly to a disorder known as hypophosphatasia, a disorder that is characterized by hypercalcemia and includes skeletal defects. The character of this disorder can vary, however, depending on the specific mutation, since this determines age of onset and severity of symptoms.
^Swallow DM, Povey S, Parkar M, Andrews PW, Harris H, Pym B, Goodfellow P (May 1988). "Mapping of the gene coding for the human liver/bone/kidney isozyme of alkaline phosphatase to chromosome 1". Ann Hum Genet50 (Pt 3): 229–35. doi:10.1111/j.1469-1809.1986.tb01043.x. PMID3446011.
Khandwala HM, Mumm S, Whyte MP (2007). "Low serum alkaline phosphatase activity and pathologic fracture: case report and brief review of hypophosphatasia diagnosed in adulthood.". Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists12 (6): 676–81. doi:10.4158/ep.12.6.676. PMID17229666.
Smith M, Weiss MJ, Griffin CA, et al. (1988). "Regional assignment of the gene for human liver/bone/kidney alkaline phosphatase to chromosome 1p36.1-p34.". Genomics2 (2): 139–43. doi:10.1016/0888-7543(88)90095-X. PMID3410475.
Garattini E, Hua JC, Pan YC, Udenfriend S (1986). "Human liver alkaline phosphatase, purification and partial sequencing: homology with the placental isozyme.". Arch. Biochem. Biophys.245 (2): 331–7. doi:10.1016/0003-9861(86)90223-7. PMID3954357.
Sato N, Takahashi Y, Asano S (1994). "Preferential usage of the bone-type leader sequence for the transcripts of liver/bone/kidney-type alkaline phosphatase gene in neutrophilic granulocytes.". Blood83 (4): 1093–101. PMID7509208.
Orimo H, Hayashi Z, Watanabe A, et al. (1995). "Novel missense and frameshift mutations in the tissue-nonspecific alkaline phosphatase gene in a Japanese patient with hypophosphatasia.". Hum. Mol. Genet.3 (9): 1683–4. doi:10.1093/hmg/3.9.1683. PMID7833929.
Greenberg CR, Taylor CL, Haworth JC, et al. (1993). "A homoallelic Gly317→Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian mennonites.". Genomics17 (1): 215–7. doi:10.1006/geno.1993.1305. PMID8406453.
Ozono K, Yamagata M, Michigami T, et al. (1997). "Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia.". J. Clin. Endocrinol. Metab.81 (12): 4458–61. doi:10.1210/jc.81.12.4458. PMID8954059.
Orimo H, Goseki-Sone M, Sato S, Shimada T (1997). "Detection of deletion 1154-1156 hypophosphatasia mutation using TNSALP exon amplification.". Genomics42 (2): 364–6. doi:10.1006/geno.1997.4733. PMID9192863.
Sugimoto N, Iwamoto S, Hoshino Y, Kajii E (1998). "A novel missense mutation of the tissue-nonspecific alkaline phosphatase gene detected in a patient with hypophosphatasia.". J. Hum. Genet.43 (3): 160–4. doi:10.1007/s100380050061. PMID9747027.