ABCC9 p.Ala1462Gly
| Predicted by SNAP2: | C: N (66%), D: D (80%), E: D (80%), F: D (75%), G: D (66%), H: D (71%), I: D (63%), K: D (80%), L: D (80%), M: D (66%), N: D (71%), P: D (85%), Q: D (71%), R: D (75%), S: N (61%), T: N (57%), V: D (53%), W: D (85%), Y: D (80%), |
| Predicted by PROVEAN: | C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] ABCC9/SUR2 in the brain: Implications for hippocam... Ageing Res Rev. 2015 Nov;24(Pt B):111-25. doi: 10.1016/j.arr.2015.07.007. Epub 2015 Jul 28. Nelson PT, Jicha GA, Wang WX, Ighodaro E, Artiushin S, Nichols CG, Fardo DW
ABCC9/SUR2 in the brain: Implications for hippocampal sclerosis of aging and a potential therapeutic target.
Ageing Res Rev. 2015 Nov;24(Pt B):111-25. doi: 10.1016/j.arr.2015.07.007. Epub 2015 Jul 28., [PMID:26226329]
Abstract [show]
The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium ("KATP") channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The KATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is a result of ABCC9 mutations; we discuss neurologic manifestations of this genetic syndrome. More common brain disorders linked to ABCC9 gene variants include hippocampal sclerosis of aging (HS-Aging), sleep disorders, and depression. HS-Aging is a prevalent neurological disease with pathologic features of both neurodegenerative (aberrant TDP-43) and cerebrovascular (arteriolosclerosis) disease. As to potential therapeutic intervention, the human pharmacopeia features both SUR2 agonists and antagonists, so ABCC9/SUR2 may provide a "druggable target", relevant perhaps to both HS-Aging and Alzheimer's disease. We conclude that more work is required to better understand the roles of ABCC9/SUR2 in the human brain during health and disease conditions.
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No. Sentence Comment
1213 Rosser et al. (1998) 3 Developmental delay noted in 2/3 cases Robertson et al. (1999) 2 Developmental delay/mild mental retardation in both cases Concolino et al. (2000) 1 "Psychomotor development was normal" Lazalde et al. (2000) 4 No specific mention of neurological disorders Engels et al. (2002) 1 Brain atrophy and ultrasound-confirmed "bilateral calcification of the Arteriae thalamostriatae" Grange et al. (2006) Woman and two daughters No mention of cognitive or cerebral anomaly Graziadio et al. (2011) 1 "mildly delayed psychomotor development" Scurr et al. (2010) 9 Motor or speech delay in 9/10 cases Kobayashi et al. (2010) 1 Clinical syndrome included "developmental delay" Czeschik et al. (2012) 2 Both with ABCC9 mutations, 1/2 with mild developmental delay Garcia-Gonzalez et al. (2012) 1 Delayed psychomotor development with cerebral cortical atrophy on CT scan van Bon et al. (2012) 9 previously unpublished, 1 father/daughter, 1 sib pair All with ABCC9 mutations, 3 diagnosed with intellectual disability and/or developmental delay, 8/9 with macrocephaly Hiraki et al. (2014) Father and son "mild psychomotor delay ... and an autistic disorder based on the DSM-IV" Park et al. (2014) 1 ABCC9 mutation (p.Ala1462Gly, c.4385C>G) confirmed; atrophic changes of the brain on MRI identify a single particular SNP that met criteria for a statistically significant association with a specific disease.
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ABCC9 p.Ala1462Gly 26226329:1213:1224
status: NEW