HGNC Approved Gene Symbol: INPP1
Cytogenetic location: 2q32.2 Genomic coordinates (GRCh38): 2:190,343,589-190,371,665 (from NCBI)
Cells respond to extracellular stimuli through complicated networks. Phosphatidylinositol turnover plays a key role in intracellular signaling. Inositol polyphosphate 1-phosphatase, an enzyme in the phosphatidylinositol signaling pathway, catalyzes the hydrolysis of the 1 position phosphate from inositol 1,3,4-trisphosphate (Ins(1,3,4)P3) and inositol 1,4-bisphosphate (Ins(1,4)P2) (summary by York et al., 1993).
York et al. (1993) isolated a cDNA for the human counterpart by low stringency hybridization using a cDNA encoding the bovine enzyme. The 1.74-kb human cDNA predicted a protein of 399 amino acids. The human and bovine enzymes show 84% amino acid sequence identity. Northern blot analysis of a variety of human tissues demonstrated that a 1.9-kb mRNA is ubiquitously expressed, with highest levels in pancreas and kidney.
York et al. (1993) suggested INPP1 as a candidate gene for inherited psychiatric disorders that respond to lithium ions, an inhibitor of the enzyme.
Woodcock et al. (2002) studied the role of inositol polyphosphates in cardiac hypertrophy, using primary cultures of neonatal rat ventricular cardiomyocytes as a model. Hypertrophy was induced by stimulating alpha-adrenergic receptors (see ADRA1B; 104220) or by the spontaneous contraction of dense cultures. Both hypertrophy models showed increased levels of Ins(1,4)P2 as well as the characteristic increased expression of several marker genes and increased ribosome synthesis. Transfection and overexpression of INPP1 reduced expression of hypertrophy markers and reduced the increase in ribosomal DNA transcription. Ins(1,4)P2 levels were also increased in mouse hearts hypertrophied by pressure overload. Woodcock et al. (2002) concluded that reduced INPP1 activity may have a role in cardiac hypertrophy.
By fluorescence in situ hybridization, York et al. (1993) mapped the INPP1 gene to chromosome 2q32. Okabe and Nussbaum (1995) used the Jackson Laboratory backcross DNA panel map service to map Inpp1 to mouse chromosome 1, 1.06 cM proximal to Ctla4.
Okabe, I., Nussbaum, R. L. Identification and chromosomal mapping of the mouse inositol polyphosphate 1-phosphatase gene. Genomics 30: 358-360, 1995. [PubMed: 8586440] [Full Text: https://doi.org/10.1006/geno.1995.0030]
Woodcock, E. A., Wang, B. H., Arthur, J. F., Lennard, A., Matkovich, S. J., Du, X.-J., Brown, J. H., Hannan, R. D. Inositol polyphosphate 1-phosphatase is a novel antihypertrophic factor. J. Biol. Chem. 277: 22734-22742, 2002. [PubMed: 11932254] [Full Text: https://doi.org/10.1074/jbc.M110405200]
York, J. D., Veile, R. A., Donis-Keller, H., Majerus, P. W. Cloning, heterologous expression, and chromosomal localization of human inositol polyphosphate 1-phosphatase. Proc. Nat. Acad. Sci. 90: 5833-5837, 1993. [PubMed: 8390685] [Full Text: https://doi.org/10.1073/pnas.90.12.5833]