ALPL
Chr 1alkaline phosphatase, biomineralization associated
Also known as: AP-TNAP, APTNAP, HOPS, HPPA, HPPC, HPPI, HPPO, TNALP
This gene encodes a member of the alkaline phosphatase family of proteins. There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The first three are located together on chromosome 2, while the tissue non-specific 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. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature enzyme. This enzyme may play a role in bone mineralization. Mutations in this gene have been linked to hypophosphatasia, a disorder that is characterized by hypercalcemia and skeletal defects. [provided by RefSeq, Oct 2015]
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
This gene — mechanism propensity
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.
References
ClinVar Variant Classifications
1609 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 98 | 44 | 12 | 0 | 154 |
Likely Pathogenic | 84 | 300 | 5 | 1 | 390 |
VUS | 11 | 287 | 47 | 14 | 359 |
Likely Benign | 2 | 8 | 203 | 262 | 475 |
Benign | 0 | 2 | 70 | 2 | 74 |
Conflicting | — | 150 | |||
| Total | 195 | 641 | 337 | 279 | 1,602 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →9 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap ALPL — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
ALPL · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Genes Associated With Bone Metabolism in the Saliva During Orthodontic Treatment
ACTIVE NOT 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
RECRUITINGHost 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)
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 RECRUITINGExternal Resources
Links to major genomics databases and tools