NA = not applicable

See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

In individuals with severe (perinatal and infantile) hypophosphatasia, biallelic ALPL pathogenic variants are identified in approximately 95% of individuals of European ancestry. In other clinical phenotypes, the proportion of pathogenic variants detected is difficult to estimate.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

A few larger ALPL deletions and one duplication have been reported [Spentchian et al 2006, Hacıhamdioğlu et al 2019, Huggins et al 2020, Sperelakis-Beedham et al 2021, The ALPL Gene Variant Database].

Anecdotal reports of individuals with clinical and biochemical features of adult hypophosphatasia with no detected ALPL pathogenic variant(s) suggest a potential second locus, not yet identified.