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{{Infobox_gene}}
{{Infobox_gene}}
'''Alkaline phosphatase, tissue-nonspecific isozyme''' is an [[enzyme]] that in humans is encoded by the ''ALPL'' [[gene]].<ref name="pmid3532105">{{cite journal | vauthors = Weiss MJ, Henthorn PS, Lafferty MA, Slaughter C, Raducha M, Harris H | title = Isolation and characterization of a cDNA encoding a human liver/bone/kidney-type alkaline phosphatase | journal = Proc Natl Acad Sci U S A | volume = 83 | issue = 19 | pages = 7182–6 |date=Oct 1986 | pmid = 3532105 | pmc = 386679 | doi =10.1073/pnas.83.19.7182 }}</ref><ref name="pmid3446011">{{cite journal | vauthors = Swallow DM, Povey S, Parkar M, Andrews PW, Harris H, Pym B, Goodfellow P | title = Mapping of the gene coding for the human liver/bone/kidney isozyme of alkaline phosphatase to chromosome 1 | journal = Ann Hum Genet | volume = 50 | issue = Pt 3 | pages = 229–35 |date=May 1988 | pmid = 3446011 | pmc =  | doi =10.1111/j.1469-1809.1986.tb01043.x }}</ref>
'''Alkaline phosphatase, tissue-nonspecific [[isozyme]]''' is an [[enzyme]] that in humans is encoded by the ''ALPL'' [[gene]].<ref name="pmid3532105">{{cite journal | vauthors = Weiss MJ, Henthorn PS, Lafferty MA, Slaughter C, Raducha M, Harris H | title = Isolation and characterization of a cDNA encoding a human liver/bone/kidney-type alkaline phosphatase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 83 | issue = 19 | pages = 7182–6 | date = October 1986 | pmid = 3532105 | pmc = 386679 | doi = 10.1073/pnas.83.19.7182 }}</ref><ref name="pmid3446011">{{cite journal | vauthors = Swallow DM, Povey S, Parkar M, Andrews PW, Harris H, Pym B, Goodfellow P | title = Mapping of the gene coding for the human liver/bone/kidney isozyme of alkaline phosphatase to chromosome 1 | journal = Annals of Human Genetics | volume = 50 | issue = Pt 3 | pages = 229–35 | date = July 1986 | pmid = 3446011 | pmc =  | doi = 10.1111/j.1469-1809.1986.tb01043.x }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB Summary
| section_title =  
| summary_text = There are at least four distinct but related [[alkaline phosphatase]]s: 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.<ref>{{cite web | title = Entrez Gene: ALPL alkaline phosphatase, liver/bone/kidney| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=249| accessdate = }}</ref>
}}


==References==
There are at least four distinct but related [[alkaline phosphatase]]s: 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.<ref>{{cite web | title = Entrez Gene: ALPL alkaline phosphatase, liver/bone/kidney| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=249 }}</ref> 
{{reflist}}


==Further reading==
== Clinical significance ==
{{refbegin | 2}}
 
{{PBB_Further_reading
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.
| citations =
 
*{{cite journal | author=Mornet E |title=Hypophosphatasia: the mutations in the tissue-nonspecific alkaline phosphatase gene. |journal=Hum. Mutat. |volume=15 |issue= 4 |pages= 309–15 |year= 2000 |pmid= 10737975 |doi= 10.1002/(SICI)1098-1004(200004)15:4<309::AID-HUMU2>3.0.CO;2-C }}
The severity of symptoms ranges from premature loss of deciduous teeth with no bone abnormalities to stillbirth<ref name="Hérasse_2002">{{cite journal | vauthors = Hérasse M, Spentchian M, Taillandier A, Mornet E | title = Evidence of a founder effect for the tissue-nonspecific alkaline phosphatase (TNSALP) gene E174K mutation in hypophosphatasia patients | journal = European Journal of Human Genetics | volume = 10 | issue = 10 | pages = 666–8 | date = October 2002 | pmid = 12357339 | doi = 10.1038/sj.ejhg.5200857 }}</ref> depending upon which amino acid<ref>{{cite journal | vauthors = Nasu M, Ito M, Ishida Y, Numa N, Komaru K, Nomura S, Oda K | title = Aberrant interchain disulfide bridge of tissue-nonspecific alkaline phosphatase with an Arg433→Cys substitution associated with severe hypophosphatasia | journal = The FEBS Journal | volume = 273 | issue = 24 | pages = 5612–24 | date = December 2006 | pmid = 17212778 | doi = 10.1093/oxfordjournals.jbchem.a022032 }}</ref><ref>{{cite journal | vauthors = Ishida Y, Komaru K, Ito M, Amaya Y, Kohno S, Oda K | title = Tissue-nonspecific alkaline phosphatase with an Asp(289)→Val mutation fails to reach the cell surface and undergoes proteasome-mediated degradation | journal = Journal of Biochemistry | volume = 134 | issue = 1 | pages = 63–70 | date = July 2003 | pmid = 12944372 | doi = 10.1093/jb/mvg114 }}</ref>
*{{cite journal | vauthors=Khandwala HM, Mumm S, Whyte MP |title=Low serum alkaline phosphatase activity and pathologic fracture: case report and brief review of hypophosphatasia diagnosed in adulthood. |journal=Endocrine Practice |volume=12 |issue= 6 |pages= 676–81 |year= 2007 |pmid= 17229666 |doi= 10.4158/ep.12.6.676}}
 
*{{cite journal | vauthors=Nye KE, Riley GA, Pinching AJ |title=The defect seen in the phosphatidylinositol hydrolysis pathway in HIV-infected lymphocytes and lymphoblastoid cells is due to inhibition of the inositol 1,4,5-trisphosphate 1,3,4,5-tetrakisphosphate 5-phosphomonoesterase. |journal=Clin. Exp. Immunol. |volume=89 |issue= 1 |pages= 89–93 |year= 1992 |pmid= 1321014 |doi=  10.1111/j.1365-2249.1992.tb06883.x| pmc=1554388  }}
is changed in the ALPL gene. Mutations in the ALPL gene lead to varying low activity of the enzyme tissue-nonspecific alkaline phosphatase (TNSALP) resulting in hypophosphatasia (HPP).<ref name="Fedde_1999">{{cite journal | vauthors = Fedde KN, Blair L, Silverstein J, Coburn SP, Ryan LM, Weinstein RS, Waymire K, Narisawa S, Millán JL, MacGregor GR, Whyte MP | title = Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia | journal = Journal of Bone and Mineral Research | volume = 14 | issue = 12 | pages = 2015–26 | date = December 1999 | pmid = 10620060 | doi = 10.1359/jbmr.1999.14.12.2015 | pmc = 3049802 }}</ref> There are different clinical forms of HPP which can be inherited by an autosomal recessive trait or autosomal dominant trait,<ref name="Hérasse_2002" /> the former causing more severe forms of the disease. Alkaline phosphatase allows for mineralization of calcium and phosphorus by bones and teeth.<ref name="Fedde_1999" /> ALPL gene mutation leads to insufficient TNSALP enzyme and allows for an accumulation of chemicals such as inorganic pyrophosphate<ref name="Fedde_1999" /> to indirectly cause elevated calcium levels in the body and lack of bone calcification. 
*{{cite journal | vauthors=Henthorn PS, Raducha M, Fedde KN |title=Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 20 |pages= 9924–8 |year= 1992 |pmid= 1409720 |doi=10.1073/pnas.89.20.9924  | pmc=50246  |display-authors=etal}}
 
*{{cite journal  | vauthors=Nishihara Y, Hayashi Y, Adachi T |title=Chemical nature of intestinal-type alkaline phosphatase in human kidney. |journal=Clin. Chem. |volume=38 |issue= 12 |pages= 2539–42 |year= 1993 |pmid= 1458595 |doi=  |display-authors=etal}}
The mutation E174K, where a glycine is converted to an alanine amino acid at the 571st position of its respective polypeptide chain, is a result of an ancestral mutation that occurred in Caucasians and shows a mild form of HPP.<ref name="Hérasse_2002" />  
*{{cite journal | vauthors=Fedde KN, Whyte MP |title=Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. |journal=Am. J. Hum. Genet. |volume=47 |issue= 5 |pages= 767–75 |year= 1990 |pmid= 2220817 |doi= | pmc=1683690  }}
 
*{{cite journal | vauthors=Kishi F, Matsuura S, Kajii T |title=Nucleotide sequence of the human liver-type alkaline phosphatase cDNA. |journal=Nucleic Acids Res. |volume=17 |issue= 5 |pages= 2129 |year= 1989 |pmid= 2928120 |doi=10.1093/nar/17.5.2129  | pmc=317555  }}
== References ==
*{{cite journal | vauthors=Weiss MJ, Ray K, Henthorn PS |title=Structure of the human liver/bone/kidney alkaline phosphatase gene. |journal=J. Biol. Chem. |volume=263 |issue= 24 |pages= 12002–10 |year= 1988 |pmid= 3165380 |doi= |display-authors=etal}}
{{reflist|32em}}
*{{cite journal | vauthors=Weiss MJ, Cole DE, Ray K |title=A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue= 20 |pages= 7666–9 |year= 1988 |pmid= 3174660 |doi=10.1073/pnas.85.20.7666  | pmc=282253  |display-authors=etal}}
{{clear}}
*{{cite journal | vauthors=Smith M, Weiss MJ, Griffin CA |title=Regional assignment of the gene for human liver/bone/kidney alkaline phosphatase to chromosome 1p36.1-p34. |journal=Genomics |volume=2 |issue= 2 |pages= 139–43 |year= 1988 |pmid= 3410475 |doi=10.1016/0888-7543(88)90095-X  |display-authors=etal}}
== Further reading ==
*{{cite journal | vauthors=Garattini E, Hua JC, Pan YC, Udenfriend S |title=Human liver alkaline phosphatase, purification and partial sequencing: homology with the placental isozyme. |journal=Arch. Biochem. Biophys. |volume=245 |issue= 2 |pages= 331–7 |year= 1986 |pmid= 3954357 |doi=10.1016/0003-9861(86)90223-7 }}
{{refbegin|32em}}
*{{cite journal | vauthors=Goldstein DJ, Blasco L, Harris H |title=Placental alkaline phosphatase in nonmalignant human cervix. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=77 |issue= 7 |pages= 4226–8 |year= 1981 |pmid= 6933471 |doi=10.1073/pnas.77.7.4226  | pmc=349804  }}
* {{cite journal | vauthors = Mornet E | title = Hypophosphatasia: the mutations in the tissue-nonspecific alkaline phosphatase gene | journal = Human Mutation | volume = 15 | issue = 4 | pages = 309–15 | year = 2000 | pmid = 10737975 | doi = 10.1002/(SICI)1098-1004(200004)15:4<309::AID-HUMU2>3.0.CO;2-C }}
*{{cite journal | vauthors=Sato N, Takahashi Y, Asano S |title=Preferential usage of the bone-type leader sequence for the transcripts of liver/bone/kidney-type alkaline phosphatase gene in neutrophilic granulocytes. |journal=Blood |volume=83 |issue= 4 |pages= 1093–101 |year= 1994 |pmid= 7509208 |doi=  }}
* {{cite journal | vauthors = Khandwala HM, Mumm S, Whyte MP | title = Low serum alkaline phosphatase activity and pathologic fracture: case report and brief review of hypophosphatasia diagnosed in adulthood | journal = Endocrine Practice | volume = 12 | issue = 6 | pages = 676–81 | year = 2007 | pmid = 17229666 | doi = 10.4158/ep.12.6.676 }}
*{{cite journal | vauthors=Orimo H, Hayashi Z, Watanabe A |title=Novel missense and frameshift mutations in the tissue-nonspecific alkaline phosphatase gene in a Japanese patient with hypophosphatasia. |journal=Hum. Mol. Genet. |volume=3 |issue= 9 |pages= 1683–4 |year= 1995 |pmid= 7833929 |doi=10.1093/hmg/3.9.1683  |display-authors=etal}}
* {{cite journal | vauthors = Nye KE, Riley GA, Pinching AJ | title = The defect seen in the phosphatidylinositol hydrolysis pathway in HIV-infected lymphocytes and lymphoblastoid cells is due to inhibition of the inositol 1,4,5-trisphosphate 1,3,4,5-tetrakisphosphate 5-phosphomonoesterase | journal = Clinical and Experimental Immunology | volume = 89 | issue = 1 | pages = 89–93 | date = July 1992 | pmid = 1321014 | pmc = 1554388 | doi = 10.1111/j.1365-2249.1992.tb06883.x }}
*{{cite journal | vauthors=Greenberg CR, Taylor CL, Haworth JC |title=A homoallelic Gly317→Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian mennonites. |journal=Genomics |volume=17 |issue= 1 |pages= 215–7 |year= 1993 |pmid= 8406453 |doi= 10.1006/geno.1993.1305 |display-authors=etal}}
* {{cite journal | vauthors = Henthorn PS, Raducha M, Fedde KN, Lafferty MA, Whyte MP | title = Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 20 | pages = 9924–8 | date = October 1992 | pmid = 1409720 | pmc = 50246 | doi = 10.1073/pnas.89.20.9924 }}
*{{cite journal | vauthors=Ozono K, Yamagata M, Michigami T |title=Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia. |journal=J. Clin. Endocrinol. Metab. |volume=81 |issue= 12 |pages= 4458–61 |year= 1997 |pmid= 8954059 |doi=10.1210/jc.81.12.4458  |display-authors=etal}}
* {{cite journal | vauthors = Nishihara Y, Hayashi Y, Adachi T, Koyama I, Stigbrand T, Hirano K | title = Chemical nature of intestinal-type alkaline phosphatase in human kidney | journal = Clinical Chemistry | volume = 38 | issue = 12 | pages = 2539–42 | date = December 1992 | pmid = 1458595 | doi = }}
*{{cite journal | vauthors=Orimo H, Goseki-Sone M, Sato S, Shimada T |title=Detection of deletion 1154-1156 hypophosphatasia mutation using TNSALP exon amplification. |journal=Genomics |volume=42 |issue= 2 |pages= 364–6 |year= 1997 |pmid= 9192863 |doi= 10.1006/geno.1997.4733 }}
* {{cite journal | vauthors = Fedde KN, Whyte MP | title = Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study | journal = American Journal of Human Genetics | volume = 47 | issue = 5 | pages = 767–75 | date = November 1990 | pmid = 2220817 | pmc = 1683690 | doi =  }}
*{{cite journal | vauthors=Sugimoto N, Iwamoto S, Hoshino Y, Kajii E |title=A novel missense mutation of the tissue-nonspecific alkaline phosphatase gene detected in a patient with hypophosphatasia. |journal=J. Hum. Genet. |volume=43 |issue= 3 |pages= 160–4 |year= 1998 |pmid= 9747027 |doi=10.1007/s100380050061 }}
* {{cite journal | vauthors = Kishi F, Matsuura S, Kajii T | title = Nucleotide sequence of the human liver-type alkaline phosphatase cDNA | journal = Nucleic Acids Research | volume = 17 | issue = 5 | pages = 2129 | date = March 1989 | pmid = 2928120 | pmc = 317555 | doi = 10.1093/nar/17.5.2129 }}
}}
* {{cite journal | vauthors = Weiss MJ, Ray K, Henthorn PS, Lamb B, Kadesch T, Harris H | title = Structure of the human liver/bone/kidney alkaline phosphatase gene | journal = The Journal of Biological Chemistry | volume = 263 | issue = 24 | pages = 12002–10 | date = August 1988 | pmid = 3165380 | doi =  }}
* {{cite journal | vauthors = Weiss MJ, Cole DE, Ray K, Whyte MP, Lafferty MA, Mulivor RA, Harris H | title = A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 20 | pages = 7666–9 | date = October 1988 | pmid = 3174660 | pmc = 282253 | doi = 10.1073/pnas.85.20.7666 }}
* {{cite journal | vauthors = Smith M, Weiss MJ, Griffin CA, Murray JC, Buetow KH, Emanuel BS, Henthorn PS, Harris H | title = Regional assignment of the gene for human liver/bone/kidney alkaline phosphatase to chromosome 1p36.1-p34 | journal = Genomics | volume = 2 | issue = 2 | pages = 139–43 | date = February 1988 | pmid = 3410475 | doi = 10.1016/0888-7543(88)90095-X }}
* {{cite journal | vauthors = Garattini E, Hua JC, Pan YC, Udenfriend S | title = Human liver alkaline phosphatase, purification and partial sequencing: homology with the placental isozyme | journal = Archives of Biochemistry and Biophysics | volume = 245 | issue = 2 | pages = 331–7 | date = March 1986 | pmid = 3954357 | doi = 10.1016/0003-9861(86)90223-7 }}
* {{cite journal | vauthors = Goldstein DJ, Blasco L, Harris H | title = Placental alkaline phosphatase in nonmalignant human cervix | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 77 | issue = 7 | pages = 4226–8 | date = July 1980 | pmid = 6933471 | pmc = 349804 | doi = 10.1073/pnas.77.7.4226 }}
* {{cite journal | vauthors = Sato N, Takahashi Y, Asano S | title = Preferential usage of the bone-type leader sequence for the transcripts of liver/bone/kidney-type alkaline phosphatase gene in neutrophilic granulocytes | journal = Blood | volume = 83 | issue = 4 | pages = 1093–101 | date = February 1994 | pmid = 7509208 | doi =  }}
* {{cite journal | vauthors = Orimo H, Hayashi Z, Watanabe A, Hirayama T, Hirayama T, Shimada T | title = Novel missense and frameshift mutations in the tissue-nonspecific alkaline phosphatase gene in a Japanese patient with hypophosphatasia | journal = Human Molecular Genetics | volume = 3 | issue = 9 | pages = 1683–4 | date = September 1994 | pmid = 7833929 | doi = 10.1093/hmg/3.9.1683 }}
* {{cite journal | vauthors = Greenberg CR, Taylor CL, Haworth JC, Seargeant LE, Philipps S, Triggs-Raine B, Chodirker BN | title = A homoallelic Gly317-->Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian mennonites | journal = Genomics | volume = 17 | issue = 1 | pages = 215–7 | date = July 1993 | pmid = 8406453 | doi = 10.1006/geno.1993.1305 }}
* {{cite journal | vauthors = Ozono K, Yamagata M, Michigami T, Nakajima S, Sakai N, Cai G, Satomura K, Yasui N, Okada S, Nakayama M | title = Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 81 | issue = 12 | pages = 4458–61 | date = December 1996 | pmid = 8954059 | doi = 10.1210/jc.81.12.4458 }}
* {{cite journal | vauthors = Orimo H, Goseki-Sone M, Sato S, Shimada T | title = Detection of deletion 1154-1156 hypophosphatasia mutation using TNSALP exon amplification | journal = Genomics | volume = 42 | issue = 2 | pages = 364–6 | date = June 1997 | pmid = 9192863 | doi = 10.1006/geno.1997.4733 }}
* {{cite journal | vauthors = Sugimoto N, Iwamoto S, Hoshino Y, Kajii E | title = A novel missense mutation of the tissue-nonspecific alkaline phosphatase gene detected in a patient with hypophosphatasia | journal = Journal of Human Genetics | volume = 43 | issue = 3 | pages = 160–4 | year = 1998 | pmid = 9747027 | doi = 10.1007/s100380050061 }}
{{refend}}
{{refend}}


==External links==
== External links ==
*[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hops  GeneReviews/NCBI/NIH/UW entry on Hypophosphatasia]
*[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hops  GeneReviews/NCBI/NIH/UW entry on Hypophosphatasia]
* {{UCSC gene info|ALPL}}
* {{UCSC gene info|ALPL}}


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[[Category:Enzymes]]
[[Category:Enzymes]]

Latest revision as of 14:15, 24 October 2018

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Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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Alkaline phosphatase, tissue-nonspecific isozyme is an enzyme that in humans is encoded by the ALPL gene.[1][2]

Function

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.[3]

Clinical significance

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.

The severity of symptoms ranges from premature loss of deciduous teeth with no bone abnormalities to stillbirth[4] depending upon which amino acid[5][6]

is changed in the ALPL gene. Mutations in the ALPL gene lead to varying low activity of the enzyme tissue-nonspecific alkaline phosphatase (TNSALP) resulting in hypophosphatasia (HPP).[7] There are different clinical forms of HPP which can be inherited by an autosomal recessive trait or autosomal dominant trait,[4] the former causing more severe forms of the disease. Alkaline phosphatase allows for mineralization of calcium and phosphorus by bones and teeth.[7] ALPL gene mutation leads to insufficient TNSALP enzyme and allows for an accumulation of chemicals such as inorganic pyrophosphate[7] to indirectly cause elevated calcium levels in the body and lack of bone calcification.

The mutation E174K, where a glycine is converted to an alanine amino acid at the 571st position of its respective polypeptide chain, is a result of an ancestral mutation that occurred in Caucasians and shows a mild form of HPP.[4]

References

  1. ↑ Weiss MJ, Henthorn PS, Lafferty MA, Slaughter C, Raducha M, Harris H (October 1986). "Isolation and characterization of a cDNA encoding a human liver/bone/kidney-type alkaline phosphatase". Proceedings of the National Academy of Sciences of the United States of America. 83 (19): 7182–6. doi:10.1073/pnas.83.19.7182. PMC 386679. PMID 3532105.
  2. ↑ Swallow DM, Povey S, Parkar M, Andrews PW, Harris H, Pym B, Goodfellow P (July 1986). "Mapping of the gene coding for the human liver/bone/kidney isozyme of alkaline phosphatase to chromosome 1". Annals of Human Genetics. 50 (Pt 3): 229–35. doi:10.1111/j.1469-1809.1986.tb01043.x. PMID 3446011.
  3. ↑ "Entrez Gene: ALPL alkaline phosphatase, liver/bone/kidney".
  4. ↑ 4.0 4.1 4.2 Hérasse M, Spentchian M, Taillandier A, Mornet E (October 2002). "Evidence of a founder effect for the tissue-nonspecific alkaline phosphatase (TNSALP) gene E174K mutation in hypophosphatasia patients". European Journal of Human Genetics. 10 (10): 666–8. doi:10.1038/sj.ejhg.5200857. PMID 12357339.
  5. ↑ Nasu M, Ito M, Ishida Y, Numa N, Komaru K, Nomura S, Oda K (December 2006). "Aberrant interchain disulfide bridge of tissue-nonspecific alkaline phosphatase with an Arg433→Cys substitution associated with severe hypophosphatasia". The FEBS Journal. 273 (24): 5612–24. doi:10.1093/oxfordjournals.jbchem.a022032. PMID 17212778.
  6. ↑ Ishida Y, Komaru K, Ito M, Amaya Y, Kohno S, Oda K (July 2003). "Tissue-nonspecific alkaline phosphatase with an Asp(289)→Val mutation fails to reach the cell surface and undergoes proteasome-mediated degradation". Journal of Biochemistry. 134 (1): 63–70. doi:10.1093/jb/mvg114. PMID 12944372.
  7. ↑ 7.0 7.1 7.2 Fedde KN, Blair L, Silverstein J, Coburn SP, Ryan LM, Weinstein RS, Waymire K, Narisawa S, Millán JL, MacGregor GR, Whyte MP (December 1999). "Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia". Journal of Bone and Mineral Research. 14 (12): 2015–26. doi:10.1359/jbmr.1999.14.12.2015. PMC 3049802. PMID 10620060.

Further reading

External links

Retrieved from "https://www.wikidoc.org/index.php?title=ALPL&oldid=1530528"