The ALPL gene provides instructions for making an enzyme called tissue-nonspecific alkaline phosphatase (TNSALP). This enzyme plays an important role in the growth and development of bones and teeth. It is also active in many other tissues, particularly in the liver and kidneys. This enzyme acts as a phosphatase, which means that it removes clusters of oxygen and phosphorus atoms (phosphate groups) from other molecules.
TNSALP is essential for the process of mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding.
Health Conditions Related to Genetic Changes
About 300 mutations in the ALPL gene have been identified in people with hypophosphatasia. Most of these mutations change a single protein building block (amino acid) in TNSALP. Other mutations insert or delete genetic material in the ALPL gene or change the way the gene's instructions are used to build the enzyme.
Mutations in the ALPL gene lead to the production of an abnormal version of TNSALP that cannot participate effectively in the mineralization of developing bones and teeth. A shortage of functional TNSALP allows substances that are normally processed by the enzyme to build up in the body. Researchers believe that a buildup of one of these compounds, inorganic pyrophosphate, underlies the defective mineralization of bones and teeth in people with hypophosphatasia.
ALPL mutations that almost completely eliminate the activity of TNSALP usually result in the more severe forms of hypophosphatasia. Other mutations, which reduce but do not eliminate the activity of the enzyme, are often responsible for milder forms of the condition.More About This Health Condition
Other Names for This Gene
- alkaline phosphatase, liver/bone/kidney
- alkaline phosphomonoesterase
- tissue non-specific alkaline phosphatase
- tissue-nonspecific ALP
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Brun-Heath I, Taillandier A, Serre JL, Mornet E. Characterization of 11 novel mutations in the tissue non-specific alkaline phosphatase gene responsible for hypophosphatasia and genotype-phenotype correlations. Mol Genet Metab. 2005 Mar;84(3):273-7. Epub 2004 Dec 19. Citation on PubMed
- Mornet E, Stura E, Lia-Baldini AS, Stigbrand T, Ménez A, Le Du MH. Structural evidence for a functional role of human tissue nonspecific alkaline phosphatase in bone mineralization. J Biol Chem. 2001 Aug 17;276(33):31171-8. Epub 2001 Jun 6. Citation on PubMed
- Mornet E. Hypophosphatasia: the mutations in the tissue-nonspecific alkaline phosphatase gene. Hum Mutat. 2000;15(4):309-15. Review. Citation on PubMed
- Mornet E. Molecular Genetics of Hypophosphatasia and Phenotype-Genotype Correlations. Subcell Biochem. 2015;76:25-43. doi: 10.1007/978-94-017-7197-9_2. Review. Citation on PubMed
- Spentchian M, Brun-Heath I, Taillandier A, Fauvert D, Serre JL, Simon-Bouy B, Carvalho F, Grochova I, Mehta SG, Müller G, Oberstein SL, Ogur G, Sharif S, Mornet E. Characterization of missense mutations and large deletions in the ALPL gene by sequencing and quantitative multiplex PCR of short fragments. Genet Test. 2006 Winter;10(4):252-7. Citation on PubMed
- Spentchian M, Merrien Y, Herasse M, Dobbie Z, Gläser D, Holder SE, Ivarsson SA, Kostiner D, Mansour S, Norman A, Roth J, Stipoljev F, Taillemite JL, van der Smagt JJ, Serre JL, Simon-Bouy B, Taillandier A, Mornet E. Severe hypophosphatasia: characterization of fifteen novel mutations in the ALPL gene. Hum Mutat. 2003 Jul;22(1):105-6. Citation on PubMed
- Whyte MP. Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2016 Apr;12(4):233-46. doi: 10.1038/nrendo.2016.14. Epub 2016 Feb 19. Review. Citation on PubMed
- Whyte MP. Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. Endocr Rev. 1994 Aug;15(4):439-61. Review. Citation on PubMed
- Whyte MP. Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann N Y Acad Sci. 2010 Mar;1192:190-200. doi: 10.1111/j.1749-6632.2010.05387.x. Review. Citation on PubMed