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Gene Review

ALPP  -  alkaline phosphatase, placental

Homo sapiens

Synonyms: ALP, Alkaline phosphatase Regan isozyme, Alkaline phosphatase, placental type, PALP, PLAP, ...
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Disease relevance of ALPP


High impact information on ALPP

  • Our findings, based on two-locus and multilocus analysis using a linkage map established from reference pedigrees, suggest that there are two or more mutations causing WS, one of which (i.e., WS1) is located on chromosome 2q, between the ALPP and FN1 loci, at distances of 7.8 cM and 11.2 cM for each marker, respectively [1].
  • We have also localized PLAP-related DNA sequences mainly on chromosome 2 and to a lesser degree on chromosome 17 [3].
  • A human term (third trimester) placental alkaline phosphatase (PLAP; EC cDNA was isolated from a human placental lambda gt11 cDNA library [3].
  • A highly informative dinucleotide repeat polymorphism at the D2S211 locus linked to ALPP, FN1 and TNP1 [6].
  • The complementary DNA is the product of the germ cell AP (Nagao isozyme) gene and not of the term PLAP gene [7].

Chemical compound and disease context of ALPP

  • Alendronate-treated women with at least a 30% reduction in bone ALP had a lower risk of non-spine (RH = 0.72; CI: 0.55, 0.92) and hip fractures (RH = 0.26; CI: 0.08, 0.83) relative to those with reductions <30% [8].
  • As expected, the decrease of both bone formation markers (bone ALP and PINP) was delayed compared to that of bone resorption and significant (p < 0.05-0.01) only after 2 months of treatment in the estrogen-treated group compared to the placebo group [9].
  • RESULTS: We noted normal bilirubin, AST, ALT, and ALP levels in 14.5%, 12.3%, 11.2%, and 26.4% of cases of acute biliary pancreatitis respectively [10].
  • The other ALP isozyme of FL cells had properties common to hepatoma ALP with regard to L-phenylalanine sensitivity, inhibition by ethylenediaminetetraacetate, inactivation by urea, and antigen site, but differed from it in electrophoretic mobility, sensitivity to L-leucine and L-homoarginine, and the presence of another antigen site [11].
  • As bone resorption markers, urinary free and total deoxypyridinoline as well as urinary collagen type I C-terminal telopeptide were measured; as bone formation markers, serum bone type and total alkaline phosphatase (BALP and ALP) levels along with osteocalcin (OC) were used [12].

Biological context of ALPP


Anatomical context of ALPP

  • In addition to these enzymes, there is a heat-stable activity in the thymus and testis that is similar but not identical to the PLAP (the PLAP-like enzyme) [2].
  • With transamidase competent HeLa cell RM, anti-PLAP or anti-epitope antibody coprecipitated both Gaa1p and Gpi8p consistent with the assembly of the proprotein into a Gaa1p:Gpi8p-containing complex [16].
  • When RM from K562 mutant K cells which lack Gpi8p were used, anti-PLAP antibody coprecipitated Gaa1p [16].
  • A phospholipase A2-activating protein (PLAP) stimulates human neutrophil aggregation and release of lysosomal enzymes, superoxide, and eicosanoids [17].
  • PLAP was detected in gouty synovial fluid by immunodot blotting and ELISA assays and expressed the same characteristics as PLAP identified from other sources [18].

Associations of ALPP with chemical compounds


Other interactions of ALPP


Analytical, diagnostic and therapeutic context of ALPP

  • The number of molecules per A431 cell was estimated by radioimmunoassay at 7.5 X 10(5), a value significantly higher than that observed for HeLa TCRC-1 cells (5 X 10(4) which express the S-variant of PLAP, also referred to as the Regan isozyme [21].
  • Since PLAP and GCAP cannot be distinguished using immunohistochemistry, the expression of these isozymes was studied at the molecular level using a reverse transcriptase-polymerase chain reaction (RT-PCR) approach, in combination with a primer extension assay [5].
  • Relative affinity was determined for a series of PLAP mutants, in which one, two or three amino acids were substituted for the corresponding wt GCAP residues by site-directed mutagenesis [22].
  • OBJECTIVE: To compare the efficacy of arthroscopic lavage plus administration of corticosteroids (ALC), arthroscopic lavage plus administration of placebo (ALP), and joint aspiration plus administration of corticosteroids (JAC) in knee arthritis, and to evaluate whether clinical or histologic characteristics determine outcome [23].
  • Although this strong SMF exposure did not affect cell proliferation, it up-regulated cell differentiation and matrix synthesis as determined by ALP and alizarin red stainings, respectively [24].


  1. Waardenburg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: first report of the WS consortium. Farrer, L.A., Grundfast, K.M., Amos, J., Arnos, K.S., Asher, J.H., Beighton, P., Diehl, S.R., Fex, J., Foy, C., Friedman, T.B. Am. J. Hum. Genet. (1992) [Pubmed]
  2. Two gene duplication events in the evolution of the human heat-stable alkaline phosphatases. Knoll, B.J., Rothblum, K.N., Longley, M. Gene (1987) [Pubmed]
  3. Cloning, sequencing, and chromosomal localization of human term placental alkaline phosphatase cDNA. Kam, W., Clauser, E., Kim, Y.S., Kan, Y.W., Rutter, W.J. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  4. Matrix vesicles in osteomalacic hypophosphatasia bone contain apatite-like mineral crystals. Anderson, H.C., Hsu, H.H., Morris, D.C., Fedde, K.N., Whyte, M.P. Am. J. Pathol. (1997) [Pubmed]
  5. Heterogeneity in alkaline phosphatase isozyme expression in human testicular germ cell tumours: An enzyme-/immunohistochemical and molecular analysis. Roelofs, H., Manes, T., Janszen, T., Millán, J.L., Oosterhuis, J.W., Looijenga, L.H. J. Pathol. (1999) [Pubmed]
  6. A highly informative dinucleotide repeat polymorphism at the D2S211 locus linked to ALPP, FN1 and TNP1. Barber, T.D., Morell, R., Johnson, D.H., Asher, J.H., Friedman, T.B. Hum. Mol. Genet. (1993) [Pubmed]
  7. Expression of a Nagao-type, phosphatidylinositol-glycan anchored alkaline phosphatase in human choriocarcinomas. Lowe, M.E., Strauss, A.W. Cancer Res. (1990) [Pubmed]
  8. Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. Bauer, D.C., Black, D.M., Garnero, P., Hochberg, M., Ott, S., Orloff, J., Thompson, D.E., Ewing, S.K., Delmas, P.D. J. Bone Miner. Res. (2004) [Pubmed]
  9. Short-term effects of new synthetic conjugated estrogens on biochemical markers of bone turnover. Garnero, P., Stevens, R.E., Ayres, S.A., Phelps, K.V. Journal of clinical pharmacology. (2002) [Pubmed]
  10. How often are liver function tests normal in acute biliary pancreatitis? Dholakia, K., Pitchumoni, C.S., Agarwal, N. J. Clin. Gastroenterol. (2004) [Pubmed]
  11. A hepatoma-associated alkaline phosphatase, the Kasahara isozyme, compared with one of the isozymes of FL amnion cells. Higashino, K., Kudo, S., Otani, R., Yamamura, Y. Ann. N. Y. Acad. Sci. (1975) [Pubmed]
  12. Short-term treatment with troglitazone decreases bone turnover in patients with type 2 diabetes mellitus. Okazaki, R., Miura, M., Toriumi, M., Taguchi, M., Hirota, Y., Fukumoto, S., Fujita, T., Tanaka, K., Takeuchi, A. Endocr. J. (1999) [Pubmed]
  13. Chromosomes, genes, and development of testicular germ cell tumors. von Eyben, F.E. Cancer Genet. Cytogenet. (2004) [Pubmed]
  14. Confirmation of the location of a Waardenburg syndrome type I mutation on human chromosome 2q. Tight linkage to FN1 and ALPP. Asher, J.H., Morell, R., Friedman, T.B. Ann. N. Y. Acad. Sci. (1991) [Pubmed]
  15. Enzyme immunoassay of human placental and germ-cell alkaline phosphatase in serum. Hendrix, P.G., Hoylaerts, M.F., Nouwen, E.J., De Broe, M.E. Clin. Chem. (1990) [Pubmed]
  16. Proprotein interaction with the GPI transamidase. Chen, R., Anderson, V., Hiroi, Y., Medof, M.E. J. Cell. Biochem. (2003) [Pubmed]
  17. A phospholipase A2-activating protein (PLAP) stimulates human neutrophil aggregation and release of lysosomal enzymes, superoxide, and eicosanoids. Bomalaski, J.S., Baker, D.G., Brophy, L., Resurreccion, N.V., Spilberg, I., Muniain, M., Clark, M.A. J. Immunol. (1989) [Pubmed]
  18. Monosodium urate crystals stimulate phospholipase A2 enzyme activities and the synthesis of a phospholipase A2-activating protein. Bomalaski, J.S., Baker, D.G., Brophy, L.M., Clark, M.A. J. Immunol. (1990) [Pubmed]
  19. Mutation of a single amino acid converts germ cell alkaline phosphatase to placental alkaline phosphatase. Watanabe, T., Wada, N., Kim, E.E., Wyckoff, H.W., Chou, J.Y. J. Biol. Chem. (1991) [Pubmed]
  20. Infantile hypophosphatasia: enzymatic defect explored with alkaline phosphatase-deficient skin fibroblasts in culture. Whyte, M.P., Rettinger, S.D., Vrabel, L.A. Calcif. Tissue Int. (1987) [Pubmed]
  21. Characterization of the placental alkaline phosphatase-like (Nagao) isozyme on the surface of A431 human epidermoid carcinoma cells. Jemmerson, R., Shah, N., Takeya, M., Fishman, W.H. Cancer Res. (1985) [Pubmed]
  22. Site-directed mutagenesis and epitope-mapped monoclonal antibodies define a catalytically important conformational difference between human placental and germ cell alkaline phosphatase. Hoylaerts, M.F., Millán, J.L. Eur. J. Biochem. (1991) [Pubmed]
  23. Comparison of efficacy of arthroscopic lavage plus administration of corticosteroids, arthroscopic lavage plus administration of placebo, and joint aspiration plus administration of corticosteroids in arthritis of the knee: A randomized controlled trial. van Oosterhout, M., Sont, J.K., Bajema, I.M., Breedveld, F.C., van Laar, J.M. Arthritis Rheum. (2006) [Pubmed]
  24. Strong static magnetic field stimulates bone formation to a definite orientation in vitro and in vivo. Kotani, H., Kawaguchi, H., Shimoaka, T., Iwasaka, M., Ueno, S., Ozawa, H., Nakamura, K., Hoshi, K. J. Bone Miner. Res. (2002) [Pubmed]
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