Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

GRIN2B

HGNC:4586 (protein-coding gene)

glutamate ionotropic receptor NMDA type subunit 2B

Unique Cases:
27
Disorders:
ID, ASD, EP, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
GRIN2B is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:26875626, PubMed:26919761, PubMed:28126851, PubMed:8768735). Sensitivity to glutamate and channel kinetics depend... (Source: Uniprot)
Previous symbols
NMDAR2B
Alias symbols
GluN2B, NR2B
Chromosomal Location
12p13.1
Genomic Coordinates
GRCh37:chr12:13714410-14133022
GRCh38:chr12:13537337-13982012
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

10.82

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.06

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive3 Supportive2 Strong2

Publications:

Husson T et. al., Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use., Transl Psychiatry, 2020
Lemke JR et. al., GRIN2B mutations in West syndrome and intellectual disability with focal epilepsy., Ann Neurol, 2014
Trujillano D et. al., Clinical exome sequencing: results from 2819 samples reflecting 1000 families., Eur J Hum Genet, 2017
De Rubeis S et. al., Synaptic, transcriptional and chromatin genes disrupted in autism., Nature, 2014
O'Roak BJ et. al., Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders., Science, 2012
O'Roak BJ et. al., Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations., Nature, 2012
Endele S et. al., Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes., Nat Genet, 2010
Coe BP et. al., Refining analyses of copy number variation identifies specific genes associated with developmental delay., Nat Genet, 2014
Guo H et. al., Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model., Mol Autism, 2018
Chérot E et. al., Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients., Clin Genet, 2018
Harripaul R et. al., Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families., Mol Psychiatry, 2018
Wang T et. al., De novo genic mutations among a Chinese autism spectrum disorder cohort., Nat Commun, 2016
Grozeva D et. al., Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability., Hum Mutat, 2015
Kenny EM et. al., Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders., Mol Psychiatry, 2014

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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