AlphaFold predicted structure
ALPL · P05186
Mean pLDDT
93.3/ 100
Very high
524 residues
Confidence breakdown
- Very high(≥ 90)90%
- Confident(70–90)2%
- Low(50–70)2%
- Very low(< 50)6%
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AlphaFold (Jumper et al., 2021) · CC BY 4.0
ALPL
Chr 1p36.12alkaline phosphatase, biomineralization associated
- Aliases:
- TNSALP, TNALP, TNAP
- MANE:
- ENST00000374840.8
Annotations refreshed 1 month ago.
Predicted protein structure
Clinical relevance (Genomics England PanelApp)
Diagnostic Grade (Green)
DDG2P
BIALLELIC, autosomal or pseudoautosomalEarly onset or syndromic epilepsy
BIALLELIC, autosomal or pseudoautosomalFetal anomalies
BOTH monoallelic and biallelic, autosomal or pseudoautosomalHypophosphataemia or rickets
BIALLELIC, autosomal or pseudoautosomalLikely inborn error of metabolism
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomalOsteogenesis imperfecta
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomalRare syndromic craniosynostosis or isolated multisuture synostosis
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomalSkeletal dysplasia
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
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Disease associations (Open Targets)
hypophosphatasia
0.87infantile hypophosphatasia
0.83adult hypophosphatasia
0.76odontohypophosphatasia
0.67childhood hypophosphatasia
0.66osteogenesis imperfecta
0.55hereditary disease
0.54ALPL-related autosomal recessive hypophosphatasia
0.52perinatal lethal hypophosphatasia
0.51nephrolithiasis
0.50
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Protein function (UniProt)
Alkaline phosphatase, tissue-nonspecific isozyme
Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has broad substrate specificity and can hydrolyze a considerable variety of compounds: however, only a few substrates, such as diphosphate (inorganic pyrophosphate; PPi), pyridoxal 5'-phosphate (PLP) and N-phosphocreatine are natural substrates (PubMed:12162492, PubMed:2220817). Plays an essential role in skeletal and dental mineralization via its ability to hydrolyze extracellular diphosphate, a potent mineralization inhibitor, to phosphate: it thereby promotes hydroxyapatite crystal formation and increases inorganic phosphate concentration (PubMed:23688511, PubMed:25982064). Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix (By similarity). Also promotes dephosphorylation of osteopontin (SSP1), an inhibitor of hydroxyapatite crystallization in its phosphorylated state; it is however unclear whether ALPL/TNAP mediates SSP1 dephosphorylation via a direct or indirect manner (By similarity). Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable form of vitamin B6, in order to provide a sufficient amount of PLP in the brain, an essential cofactor for enzymes catalyzing the synthesis of diverse neurotransmitters (PubMed:20049532, PubMed:2220817). Additionally, also able to mediate ATP degradation in a stepwise manner to adenosine, thereby regulating the availability of ligands for purinergic receptors (By similarity). Also capable of dephosphorylating microbial products, such as lipopolysaccharides (LPS) as well as other phosphorylated small-molecules, such as poly-inosine:cytosine (poly I:C) (PubMed:28448526). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating hydrolysis of N-phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation (By similarity). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity)
Diseases associated with ALPL
Curated MONDO disease pages that list ALPL among their top associated genes.