ALPL
Chr 1alkaline phosphatase, biomineralization associated
Also known as: AP-TNAP, APTNAP, HOPS, HPPA, HPPC, HPPI, HPPO, TNALP
This gene encodes tissue-nonspecific alkaline phosphatase, a membrane-bound enzyme that hydrolyzes inorganic pyrophosphate and other phosphate compounds to promote bone and tooth mineralization, and also dephosphorylates pyridoxal 5'-phosphate for vitamin B6 metabolism in the brain. Mutations cause hypophosphatasia, which presents across a spectrum from severe infantile forms with life-threatening skeletal defects to milder childhood, adult, and dental-only variants. Inheritance can be either autosomal recessive (typically for severe early-onset forms) or autosomal dominant (often for milder presentations).
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ALPL · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA
ACTIVE NOT RECRUITINGNatural History Study of Patients With Hypophosphatasia (HPP)
RECRUITINGGenes Associated With Bone Metabolism in the Saliva During Orthodontic Treatment
ACTIVE NOT RECRUITINGUnited States Hypophosphatasia Molecular Research Center
ACTIVE NOT RECRUITINGHost Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA. a Prospective Study Will Evaluate the Performance of Direct LS-TA in Triage Febrile Patients Into Major Categories of Infections: Viral, Bacterial or Active Tuberculosis.
NOT YET RECRUITINGCharacteristics of Hypophosphatasia in Adult Patients in Rheumatology and Their Value in Developing an Algorithm to HPP-diagnosis - the COHIR Multi-center Study
RECRUITINGThe Effect of Monoallelic Variants in the ALPL Gene on the Natural Course of Hypophosphatasia in Russia
RECRUITINGExternal Resources
Links to major genomics databases and tools