ALPL Gene: Alkaline Phosphatase, Liver/Bone/Kidney
Genetic and functional insights into ALPL, its role in hypophosphatasia, and clinical significance.
Gene Information Card
| Symbol | ALPL |
|---|---|
| Full Name | Alkaline Phosphatase, Biomineralization Associated |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.12 |
| NCBI Gene ID | 249 ncbi.nlm.nih.gov/gene/249 |
| Ensembl ID | ENSG00000162551 |
| UniProt ID | P05186 |
| OMIM ID | 171760 |
| HGNC ID | 438 |
| Aliases | TNSALP, AP-TNAP, HOPS, TNAP |
Description
The ALPL gene encodes tissue-nonspecific alkaline phosphatase (TNSALP), a membrane-bound enzyme that hydrolyzes pyrophosphate, pyridoxal-5'-phosphate, and other phosphocompounds. It is essential for bone mineralization and is expressed primarily in liver, bone, and kidney. Loss-of-function mutations cause hypophosphatasia (HPP), a disorder characterized by defective skeletal mineralization.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypophosphatasia (HPP) | Loss-of-function mutations reduce TNSALP activity, leading to accumulation of inorganic pyrophosphate (PPi), an inhibitor of hydroxyapatite crystal formation, impairing bone and tooth mineralization. | ClinVar, OMIM |
| Odontohypophosphatasia | Mild ALPL mutations cause premature tooth loss and dental defects without systemic skeletal disease. | ClinVar, OMIM |
| Infantile Hypophosphatasia | Severe ALPL mutations (e.g., homozygous or compound heterozygous) result in profound skeletal hypomineralization, respiratory failure, and high mortality. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Bone (osteoblasts) | 8.3 | Medium |
| Kidney | 6.1 | Low |
| Small intestine | 2.0 | Low |
| Placenta | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.2 | High expression |
| Saos-2 (osteosarcoma) | 10.8 | High expression |
| HEK293 (embryonic kidney) | 4.5 | Moderate expression |
| MCF7 (breast) | 0.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.571G>A (p.Glu191Lys) | Missense | Common in European HPP | Loss of function |
| c.979T>C (p.Phe327Leu) | Missense | ~5% in HPP | Loss of function |
| c.346G>A (p.Ala116Thr) | Missense | ~3% in HPP | Loss of function |
| c.1559delT (p.Leu520Trpfs*86) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most ALPL mutations are loss-of-function, reducing TNSALP enzymatic activity, leading to pyrophosphate accumulation and impaired bone mineralization.
Gain of Function (GOF)
No gain-of-function mutations are clinically reported for ALPL.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects in heterozygous carriers, but autosomal recessive inheritance is typical.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004035 – alkaline phosphatase activity | • GO:0005576 – extracellular region |
| • GO:0005886 – plasma membrane | • GO:0001503 – ossification |
| • GO:0046849 – bone mineralization |
Pathways
• Pyridoxal phosphate salvage pathway
• Phosphate metabolism
• Bone mineralization (Reactome: R-HSA-1474228)
Protein Summary
Tissue-nonspecific alkaline phosphatase (TNSALP) is a 524-amino-acid glycoprotein anchored to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor. It functions as a homodimer, requiring zinc and magnesium ions for catalytic activity. TNSALP dephosphorylates substrates such as inorganic pyrophosphate (PPi) and pyridoxal-5'-phosphate (PLP), regulating bone mineralization and vitamin B6 metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALPL Knockout HEK293 Cell Line | EDC08024 | Human | 249 | Details Get a Quote |
| ALPL Knockout HeLa Cell Line | EDJ-KQ22028 | Human | 249 | Details Get a Quote |
| ALPL Knockout A-549 Cell Line | EDJ-KQ61079 | Human | 249 | Details Get a Quote |
| ALPL Knockout HCT 116 Cell Line | EDJ-KQ69561 | Human | 249 | Details Get a Quote |
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