|Institutional Source||Beutler Lab|
|Gene Name||alkaline phosphatase, liver/bone/kidney|
|Synonyms||TNSALP, TNAP, Akp-2, Akp2|
|Is this an essential gene?||Essential (E-score: 1.000)|
|Stock #||R8686 (G1)|
|Chromosomal Location||137741733-137796384 bp(-) (GRCm38)|
|Type of Mutation||missense|
|DNA Base Change (assembly)||A to T at 137743801 bp (GRCm38)|
|Amino Acid Change||Histidine to Glutamine at position 341 (H341Q)|
|Ref Sequence||ENSEMBL: ENSMUSP00000030551 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000030551]|
AA Change: H341Q
PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
AA Change: H341Q
|Meta Mutation Damage Score||0.9632|
|Coding Region Coverage||
|Validation Efficiency||100% (58/58)|
FUNCTION: This gene encodes a preproprotein that is proteolytically cleaved to yield a signal peptide and a proproptein that is subsequently processed to generate the active mature peptide. The encoded protein is a membrane-bound glycosylated enzyme that catalyzes the hydrolysis of phosphate esters at alkaline pH. The mature peptide maintains the ratio of inorganic phosphate to inorganic pyrophosphate required for bone mineralization. Mice that lack this enzyme show symptoms of osteomalacia, softening of the bones. In humans, mutations in this gene are associated with hypophosphatasia, an inherited metabolic bone disease in which deficiency of this enzyme inhibits bone mineralization leading to skeletal defects. Mutations in the mouse gene mirror the symptoms of human hypophosphatasia. A pseudogene of this gene is present on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]
PHENOTYPE: Males hemizygous for a null mutation exhibit reduced body size, shortened hindlimbs and tail, osteomalacia, and markedly reduced plasma phosphate levels due to impaired kidney reabsorption. Female heterozygotes exhibit milder symptoms. [provided by MGI curators]
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Alpl||
(F):5'- ACAGGCTGCTTCGCTGTATC -3'
(R):5'- ACTTGGCCATGAGATGCCTG -3'
(F):5'- TGTATCCCAGGGACAGGCTACTC -3'
(R):5'- CCATGAGATGCCTGAGGTAGACC -3'