Disease relevance of IMPA2

• Genetic variants in the IMPA2 gene do not confer increased risk of febrile seizures in Caucasian patients [1].
• Identification of a plasmid encoding SHV-12, TEM-1, and a variant of IMP-2 metallo-beta-lactamase, IMP-8, from a clinical isolate of Klebsiella pneumoniae [2].

Psychiatry related information on IMPA2

• The association between manic-depressive illness and IMPA2 variants supports several reports on the linkage of bipolar disorder to chromosome 18p11.2, and sustains the possible role of IMPA2 as a susceptibility gene in bipolar disorder [3].
• In our search for candidate genes for affective disorder on the short arm of chromosome 18, we cloned IMPA2, a previously unreported myo-inositol monophosphatase gene, that maps to 18p11 [4].
• The present study suggests that a promoter haplotype of IMPA2 possibly contributes to risk for bipolar disorder by elevating IMPA2 levels in the brain, albeit the genetic effect varies among populations [5].

High impact information on IMPA2

• Examination of IMPA1 and IMPA2 genes in manic-depressive patients: association between IMPA2 promoter polymorphisms and bipolar disorder [3].
• Intriguingly, two frequent single-nucleotide polymorphisms (-461C>T and -207T>C) in the IMPA2 promoter sequence and their corresponding haplotypes showed transmission disequilibrium in the Palestinian Arab trios [3].
• Collectively, these observations suggest a potential sex-dependent link between abnormalities in IMPA2 expression and calcium homeostasis in the pathophysiology of BD [6].
• These findings increase the relevance of 18p11.2 to schizophrenia susceptibility because GNAL, which has been shown previously to be implicated in schizophrenia in an independent study, is in close physical proximity to IMPA2 [4].
• Evidence for association of the myo-inositol monophosphatase 2 (IMPA2) gene with schizophrenia in Japanese samples [4].

Chemical compound and disease context of IMPA2

• Because the myo-inositol monophosphatase enzyme has been shown to be inhibited by lithium, an effective therapeutic agent for bipolar disorder, IMPA2 is a plausible positional and functional candidate gene [7].

Biological context of IMPA2

• Here we report that the genomic structure of IMPA2 is composed of eight exons, ranging in size from 46 bp to 535 bp [8].
• Altered IMPA2 gene expression and calcium homeostasis in bipolar disorder [6].
• IMPA2 promoter activity appears to be contributed by different elements in the 5' flanking region, suggesting that the gene is differentially regulated in neuronal and non-neuronal cells [9].
• Linkage and association of febrile seizures to the IMPA2 gene on human chromosome 18 [10].

Anatomical context of IMPA2

• Furthermore, IMPA2 promoter activity in both cell lines is downregulated, in a dose-dependent manner, by lithium after treatment for only 24h [9].

Associations of IMPA2 with chemical compounds

• 2. IMPA2 is therefore a candidate for genetic studies on both etiology and lithium treatment of manic-depressive illness [8].
• Two genes encoding human IMPases have so far been isolated, namely myo-inositol monophosphatase 1 (IMPA1) on chromosome 8q21.13-21.3 and myo-inositol monophosphatase 2 (IMPA2) on chromosome 18p11 [3].
• Lead(II)-binding properties of the 5'-monophosphates of adenosine (AMP2-), inosine (IMP2-), and guanosine (GMP2-) in aqueous solution. Evidence for nucleobase-lead(II) interactions [11].

Other interactions of IMPA2

• 2. In the present study, we have scanned for DNA variants in the human IMPA1 and IMPA2 genes in a pilot sample of Norwegian manic-depressive patients, followed by examination of selected polymorphisms and haplotypes in a family-based bipolar sample of Palestinian Arab proband-parent trios [3].
• Whereas most previous positive findings were not supported by subsequent studies, DRD1 and IMPA2 have been implicated in follow-up studies [12].

Analytical, diagnostic and therapeutic context of IMPA2

• The stability constants of the 1:1 complexes formed between Pb2+ and the nucleosides (Ns), adenosine and guanosine, as well as between the nucleotides (NMP2-), AMP2-, IMP2-, and GMP2-, were determined by potentiometric pH titrations in aqueous solution (25 degrees C; I = 0.1 M, NaNO3) [11].

References