Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Elsevier Science full text link Elsevier Science Free PMC article
Full text links

Actions

Review
.2016 Oct;132(2):115-121.
doi: 10.1016/j.jphs.2016.10.002. Epub 2016 Oct 19.

Human GRIN2B variants in neurodevelopmental disorders

Affiliations
Review

Human GRIN2B variants in neurodevelopmental disorders

Chun Hu et al. J Pharmacol Sci.2016 Oct.

Erratum in

Abstract

The development of whole exome/genome sequencing technologies has given rise to an unprecedented volume of data linking patient genomic variability to brain disorder phenotypes. A surprising number of variants have been found in the N-methyl-d-aspartate receptor (NMDAR) gene family, with the GRIN2B gene encoding the GluN2B subunit being implicated in many cases of neurodevelopmental disorders, which are psychiatric conditions originating in childhood and include language, motor, and learning disorders, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), developmental delay, epilepsy, and schizophrenia. The GRIN2B gene plays a crucial role in normal neuronal development and is important for learning and memory. Mutations in human GRIN2B were distributed throughout the entire gene in a number of patients with various neuropsychiatric and developmental disorders. Studies that provide functional analysis of variants are still lacking, however current analysis of de novo variants that segregate with disease cases such as intellectual disability, developmental delay, ASD or epileptic encephalopathies reveal altered NMDAR function. Here, we summarize the current reports of disease-associated variants in GRIN2B from patients with multiple neurodevelopmental disorders, and discuss implications, highlighting the importance of functional analysis and precision medicine therapies.

Keywords: Developmental delay; GluN2B/NR2B; Intellectual disability; NMDA receptor; Neuropsychiatric disorders.

Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

PubMed Disclaimer

Conflict of interest statement

S.F.T is a cofounder of NeurOp Inc., and a paid consultant of NeurOp Inc, Janssen Pharmaceuticals, and Pfizer Inc.

Figures

Fig. 1
Fig. 1. Locations of GluN2B mutations
Ribbon structures of a tetramer GluN1/GluN2B receptor (37,38) illustrates receptor architecture (light yellow: GluN1; light blue: GluN2B). The amino terminal domain (ATD) is shown, the S1 and S2 regions describe two portions of the polypeptide chain that comprise the agonist binding domain (ABD), and three transmembrane helices (M1, M3, M4) and the M2 re-entrant pore loop comprise the transmembrane domain (TM).A, Residues harboringde novo mutations are highlighted in MAGENTA, transmitted mutations in BLUE, and variants of unknown origin in ORANGE.B, Residues harboring mutations in human patients with a clear disease segregation or absent from ExAC are highlighted in CYAN. In both panels an (*) indicates that the variant results in a truncated protein. The residue alanine at position 590 is not shown due to poor resolution of crystal structure in this region. The variants V18 in the signal peptide, and Q1014, G1026, R1099, T1228, A1267, T1273, K1293, M1331, M1339, N1352, S1415, L1424, S1452 in the carboxyl terminal domain (CTD) are not present in the crystal structure and therefore not shown.
See this image and copyright information in PMC

References

    1. Akazawa C, Shigemoto R, Bessho Y, Nakanishi S, Mizuno N. Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats. J Comp Neurol. 1994;347:150–160. - PubMed
    1. Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron. 1994;12(3):529–540. - PubMed
    1. Cohen S, Greenberg ME. Communication between the synapse and the nucleus in neuronal development, plasticity, and disease. Annu Rev Cell Dev Biol. 2008;24:183–209. - PMC - PubMed
    1. Hall BJ, Ripley B, Ghosh A. NR2B signaling regulates the development of synaptic AMPA receptor current. J Neurosci. 2007;27(49):13446–13456. - PMC - PubMed
    1. Kutsuwada T, Sakimura K, Manabe T, Takayama C, Katakura N, Kushiya E, et al. Impairment of suckling response, trigeminal neuronal pattern formation, and hippocampal LTD in NMDA receptor epsilon 2 subunit mutant mice. Neuron. 1996;16:333–344. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full text links
Elsevier Science full text link Elsevier Science Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2026 Movatter.jp