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ALPL
Identifiers
Aliases ALPL, AP-TNAP, APTNAP, HOPS, TNAP, TNSALP, alkaline phosphatase, liver/bone/kidney, TNALP
External IDs MGI: 87983 HomoloGene: 37314 GeneCards: ALPL
Gene location (Human)
Chromosome 1 (human)
Chr. Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for ALPL
Genomic location for ALPL
Band 1p36.12 Start 21,509,372 bp[1]
End 21,578,412 bp[1]
RNA expression pattern
PBB GE ALPL 215783 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000478
NM_001127501
NM_001177520

NM_001287172
NM_001287176
NM_007431

RefSeq (protein)

NP_000469
NP_001120973
NP_001170991

NP_001274101
NP_031457

Location (UCSC) Chr 1: 21.51 – 21.58 Mb Chr 4: 137.74 – 137.8 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Alkaline phosphatase, tissue-nonspecific isozyme is an enzyme that in humans is encoded by the ALPL gene.[5][6]

Function[edit]

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.[7]

Clinical significance[edit]

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[8] depending upon which amino acid[9][10]

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).[11] There are different clinical forms of HPP which can be inherited by an autosomal recessive trait or autosomal dominant trait,[8] the former causing more severe forms of the disease. Alkaline phosphatase allows for mineralization of calcium and phosphorus by bones and teeth.[11] ALPL gene mutation leads to insufficient TNSALP enzyme and allows for an accumulation of chemicals such as inorganic pyrophosphate[11] 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.[8]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000162551 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028766 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ 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 386679Freely accessible. PMID 3532105. 
  6. ^ 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. 
  7. ^ "Entrez Gene: ALPL alkaline phosphatase, liver/bone/kidney". 
  8. ^ a b c 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ a b c 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. PMID 10620060. 

Further reading[edit]

External links[edit]

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