GRIN2Aglutamate receptor, ionotropic, N-methyl D-aspartate 2A
Autism Reports / Total Reports
9 / 44Rare Variants / Common Variants
169 / 5Aliases
GRIN2A, NR2A, NMDAR2AAssociated Syndromes
-Genetic Category
Rare Single Gene Mutation, Syndromic, Genetic AssociationChromosome Band
16p13.2Associated Disorders
EP, ADHD, DD/NDD, ID, EPS, ASDRelevance to Autism
Genetic association has been found between the GRIN2A gene and autism in an IMGSAC cohort (Barnby et al., 2005).
Molecular Function
The encoded protein is a subunit of N-methyl-D-aspartate (NMDA) selective glutamate receptors.
Reports related to GRIN2A (44 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Primary | Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT. | Barnby G , et al. (2005) | Yes | - |
2 | Recent Recommendation | Integrative properties of radial oblique dendrites in hippocampal CA1 pyramidal neurons. | Losonczy A and Magee JC (2006) | No | - |
3 | Recent Recommendation | Cholesterol-enriched diet affects spatial learning and synaptic function in hippocampal synapses. | Dufour F , et al. (2006) | No | - |
4 | Recent Recommendation | Zinc modulates bidirectional hippocampal plasticity by effects on NMDA receptors. | Izumi Y , et al. (2006) | No | - |
5 | Recent Recommendation | NMDA receptor function: subunit composition versus spatial distribution. | Khr G (2006) | No | - |
6 | Support | Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. | Endele S , et al. (2010) | No | ID |
7 | Support | Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy. | Klassen T , et al. (2011) | No | - |
8 | Support | Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi... | Lesca G , et al. (2012) | No | ADHD |
9 | Support | Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia. | Tarabeux J , et al. (2011) | Yes | - |
10 | Support | Diagnostic exome sequencing in persons with severe intellectual disability. | de Ligt J , et al. (2012) | No | Epilepsy, ASD |
11 | Support | Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. | Girirajan S , et al. (2013) | Yes | - |
12 | Positive Association | Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. | Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) | Yes | - |
13 | Recent Recommendation | GRIN2A mutations cause epilepsy-aphasia spectrum disorders. | Carvill GL , et al. (2013) | No | - |
14 | Recent Recommendation | Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. | Lemke JR , et al. (2013) | No | DD, ID |
15 | Recent Recommendation | GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction. | Lesca G , et al. (2013) | No | - |
16 | Support | Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation. | Venkateswaran S , et al. (2014) | No | - |
17 | Support | Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities. | Zhang Y , et al. (2015) | No | - |
18 | Support | Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms. | D'Gama AM , et al. (2015) | Yes | - |
19 | Recent Recommendation | Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease. | Johnson MR , et al. (2015) | No | - |
20 | Support | Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability | Lelieveld SH et al. (2016) | No | - |
21 | Recent Recommendation | Mechanistic Insight into NMDA Receptor Dysregulation by Rare Variants in the GluN2A and GluN2B Agonist Binding Domains. | Swanger SA , et al. (2016) | No | ASD, epilepsy/seizures |
22 | Support | Molecular Mechanism of Disease-Associated Mutations in the Pre-M1 Helix of NMDA Receptors and Potential Rescue Pharmacology. | Ogden KK , et al. (2017) | No | - |
23 | Support | Epilepsy in patients with GRIN2A alterations: Genetics, neurodevelopment, epileptic phenotype and response to anticonvulsive drugs. | von Stlpnagel C , et al. (2017) | No | DD, ID |
24 | Support | Functional Evaluation of a De Novo GRIN2A Mutation Identified in a Patient with Profound Global Developmental Delay and Refractory Epilepsy. | Chen W , et al. (2017) | No | - |
25 | Support | A de novo loss-of-function GRIN2A mutation associated with childhood focal epilepsy and acquired epileptic aphasia. | Gao K , et al. (2017) | No | - |
26 | Recent Recommendation | Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency - molecular profiling and functional rescue. | Addis L , et al. (2017) | No | - |
27 | Support | A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology. | Vissers LE , et al. (2017) | No | - |
28 | Support | Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment. | Chen XS , et al. (2017) | No | - |
29 | Support | Functional assessment of the NMDA receptor variant GluN2A R586K. | Marwick KFM , et al. (2017) | No | - |
30 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay. | Bowling KM , et al. (2017) | No | - |
31 | Support | Functional Properties of Human NMDA Receptors Associated with Epilepsy-Related Mutations of GluN2A Subunit. | Sibarov DA , et al. (2017) | No | - |
32 | Support | Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. | Lionel AC , et al. (2017) | No | - |
33 | Highly Cited | Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. | Garthwaite J , et al. (1988) | No | - |
34 | Support | Rare loss of function mutations in N-methyl-D-aspartate glutamate receptors and their contributions to schizophrenia susceptibility. | Yu Y , et al. (2018) | Yes | - |
35 | Positive Association | Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. | Pardias AF , et al. (2018) | No | - |
36 | Support | A novel missense mutation in GRIN2A causes a nonepileptic neurodevelopmental disorder. | Fernndez-Marmiesse A , et al. (2018) | No | Movement disorder |
37 | Recent recommendation | GRIN2A-related disorders: genotype and functional consequence predict phenotype. | Strehlow V , et al. (2018) | No | - |
38 | Support | De novo GRIN variants in NMDA receptor M2 channel pore-forming loop are associated with neurological diseases. | Li J , et al. (2019) | No | - |
39 | Support | Autism risk in offspring can be assessed through quantification of male sperm mosaicism. | Breuss MW , et al. (2019) | Yes | - |
40 | Support | Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability | Chevarin M et al. (2020) | No | Marfanoid habitus |
41 | Support | Next-Generation Sequencing in Korean Children With Autism Spectrum Disorder and Comorbid Epilepsy | Lee J et al. (2020) | Yes | ID, epilepsy/seizures |
42 | Support | Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression | Yin J et al. (2020) | Yes | Developmental regression, epilepsy/seizures |
43 | Support | An Epilepsy-Associated GRIN2A Rare Variant Disrupts CaMKIIñ Phosphorylation of GluN2A and NMDA Receptor Trafficking | Mota Vieira M et al. (2020) | No | - |
44 | Highly Cited | Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. | Monyer H , et al. (1994) | No | - |
Rare Variants (169)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_gain | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
- | - | copy_number_loss | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
- | - | copy_number_loss | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
- | - | copy_number_gain | Unknown | - | Unknown | 23933819 | Lemke JR , et al. (2013) | |
- | - | copy_number_loss | Unknown | - | Unknown | 23933819 | Lemke JR , et al. (2013) | |
- | - | copy_number_gain | Unknown | - | - | 28109652 | von Stlpnagel C , et al. (2017) | |
- | - | copy_number_loss | De novo | NA | Unknown | 22738016 | Lesca G , et al. (2012) | |
- | - | copy_number_loss | Familial | Maternal | - | 30544257 | Strehlow V , et al. (2018) | |
- | - | copy_number_loss | Familial | Paternal | - | 30544257 | Strehlow V , et al. (2018) | |
- | - | copy_number_loss | Familial | - | Multiplex | 30544257 | Strehlow V , et al. (2018) | |
c.3190A>G | p.Thr1064Ala | missense_variant | - | - | - | 20890276 | Endele S , et al. (2010) | |
c.428C>T | p.Thr143Ile | missense_variant | - | - | - | 22833210 | Tarabeux J , et al. (2011) | |
c.418C>G | p.Pro140Ala | missense_variant | Unknown | - | - | 29317596 | Yu Y , et al. (2018) | |
c.446C>T | p.Ala149Val | missense_variant | Unknown | - | - | 29317596 | Yu Y , et al. (2018) | |
c.2765C>T | p.Ala922Val | missense_variant | - | - | - | 22833210 | Tarabeux J , et al. (2011) | |
c.415-2A>G | - | splice_site_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.1323A>C | p.Lys441Asn | missense_variant | Unknown | - | - | 29317596 | Yu Y , et al. (2018) | |
c.1770A>C | p.Lys590Asn | missense_variant | Unknown | - | - | 29317596 | Yu Y , et al. (2018) | |
c.2650G>A | p.Asp884Asn | missense_variant | Unknown | - | - | 29317596 | Yu Y , et al. (2018) | |
c.2890C>G | p.Gln964Glu | missense_variant | Unknown | - | - | 29317596 | Yu Y , et al. (2018) | |
c.165G>A | p.Trp55Ter | stop_gained | Familial | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.1007+1G>A | - | splice_site_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.2007+2dup | - | splice_site_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.2008-1G>T | - | splice_site_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.2518C>T | p.Leu840Phe | missense_variant | Familial | - | - | 29317596 | Yu Y , et al. (2018) | |
c.2627T>C | p.Ile876Thr | missense_variant | Familial | - | - | 29317596 | Yu Y , et al. (2018) | |
c.3386A>G | p.His1129Arg | missense_variant | Unknown | - | - | 29317596 | Yu Y , et al. (2018) | |
c.3059C>G | p.Ser1020Cys | missense_variant | Unknown | - | - | 32477112 | Lee J et al. (2020) | |
- | - | copy_number_loss | Familial | Maternal | Multiplex | 23933820 | Lesca G , et al. (2013) | |
c.2998G>A | p.Val1000Met | missense_variant | Familial | - | - | 29317596 | Yu Y , et al. (2018) | |
C>T | p.(=) | synonymous_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
G>T | p.(=) | synonymous_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
c.500G>A | p.Trp167Ter | stop_gained | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1497+1G>C | - | splice_site_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1036A>T | p.Lys346Ter | stop_gained | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1613C>G | p.Ser538Ter | stop_gained | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1818G>A | p.Trp606Ter | stop_gained | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.28C>A | p.Leu10Met | missense_variant | Unknown | - | Unknown | 32722525 | Yin J et al. (2020) | |
- | - | copy_number_loss | Familial | Maternal | Multiplex | 30544257 | Strehlow V , et al. (2018) | |
c.3228C>G | p.Asn1076Lys | missense_variant | Unknown | - | - | 20890276 | Endele S , et al. (2010) | |
c.594G>A | p.Trp198Ter | stop_gained | Unknown | - | Unknown | 23933819 | Lemke JR , et al. (2013) | |
- | - | copy_number_gain | Familial | Maternal | Multiplex | 23375656 | Girirajan S , et al. (2013) | |
c.904G>T | p.Ala302Ser | missense_variant | Unknown | - | Unknown | 32722525 | Yin J et al. (2020) | |
c.1845C>A | p.Asn615Lys | missense_variant | De novo | NA | - | 20890276 | Endele S , et al. (2010) | |
C>T | p.Met788Ile | missense_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
c.2054T>C | p.Val685Ala | missense_variant | Unknown | - | - | 27839871 | Swanger SA , et al. (2016) | |
c.1552C>T | p.Arg518Cys | missense_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.1553G>A | p.Arg518His | missense_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.1592C>T | p.Thr531Met | missense_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.2191G>A | p.Asp731Asn | missense_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.2449A>G | p.Met817Val | missense_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.1818G>A | p.Trp606Ter | stop_gained | Unknown | - | - | 28109652 | von Stlpnagel C , et al. (2017) | |
c.1655C>G | p.Pro552Arg | missense_variant | De novo | NA | - | 23033978 | de Ligt J , et al. (2012) | |
c.1945C>G | p.Leu649Val | missense_variant | De novo | NA | - | 23033978 | de Ligt J , et al. (2012) | |
c.2050A>G | p.Thr684Ala | missense_variant | De novo | NA | - | 28771251 | Lionel AC , et al. (2017) | |
c.2450T>C | p.Met817Thr | missense_variant | De novo | NA | - | 28333917 | Vissers LE , et al. (2017) | |
c.1232T>A | p.Leu411Gln | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1492G>A | p.Gly498Ser | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1552C>T | p.Arg518Cys | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1595G>T | p.Gly532Val | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1642G>C | p.Ala548Pro | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1655C>G | p.Pro552Arg | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1832T>A | p.Leu611Gln | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1841A>G | p.Asn614Ser | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1903G>A | p.Ala635Thr | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1930A>G | p.Ser644Gly | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1936A>G | p.Thr646Ala | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1943A>G | p.Asn648Ser | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1945C>G | p.Leu649Val | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1959G>A | p.Met653Ile | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1961T>C | p.Ile654Thr | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2050A>G | p.Thr684Ala | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2084G>A | p.Arg695Gln | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2138T>G | p.Val713Gly | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2146G>A | p.Ala716Thr | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2197G>A | p.Ala733Thr | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2427C>A | p.Ser809Arg | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2449A>G | p.Met817Val | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2450T>C | p.Met817Thr | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2450T>G | p.Met817Arg | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2453C>A | p.Ala818Glu | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2407G>T | p.Glu803Ter | stop_gained | De novo | NA | - | 28109652 | von Stlpnagel C , et al. (2017) | |
c.4375A>G | p.Ser1459Gly | missense_variant | De novo | NA | - | 28554332 | Bowling KM , et al. (2017) | |
c.1651+1del | - | splice_site_variant | Familial | Maternal | - | 30544257 | Strehlow V , et al. (2018) | |
c.594G>A | p.Trp198Ter | stop_gained | Unknown | - | Multiplex | 30544257 | Strehlow V , et al. (2018) | |
c.2450T>C | p.Met817Thr | missense_variant | De novo | NA | - | 27479843 | Lelieveld SH et al. (2016) | |
c.2191G>A | p.Asp731Asn | missense_variant | De novo | NA | Simplex | 28182669 | Gao K , et al. (2017) | |
c.2007G>T | p.Lys669Asn | missense_variant | Unknown | - | Simplex | 23933820 | Lesca G , et al. (2013) | |
c.728C>T | p.Ala243Val | missense_variant | Unknown | - | Unknown | 23933819 | Lemke JR , et al. (2013) | |
c.869C>T | p.Ala290Val | missense_variant | Unknown | - | Unknown | 23933819 | Lemke JR , et al. (2013) | |
c.1007+1G>A | - | splice_site_variant | De novo | NA | Multiplex | 31873310 | Breuss MW , et al. (2019) | |
c.487C>T | p.Gln163Ter | stop_gained | Familial | - | Multiplex | 30544257 | Strehlow V , et al. (2018) | |
c.3827C>G | p.Ala1276Gly | missense_variant | Unknown | - | Unknown | 23933820 | Lesca G , et al. (2013) | |
- | p.phe670fs | copy_number_loss | Familial | Maternal | Multiplex | 23933820 | Lesca G , et al. (2013) | |
c.1108C>T | p.Arg370Trp | missense_variant | Unknown | - | Unknown | 23933819 | Lemke JR , et al. (2013) | |
c.2140G>A | p.Glu714Lys | missense_variant | Unknown | - | Unknown | 23933819 | Lemke JR , et al. (2013) | |
c.2179G>A | p.Ala727Thr | missense_variant | Unknown | - | Unknown | 23933819 | Lemke JR , et al. (2013) | |
c.2314A>G | p.Lys772Glu | missense_variant | Unknown | - | Unknown | 23933819 | Lemke JR , et al. (2013) | |
c.2927A>G | p.Asn976Ser | missense_variant | Unknown | - | Unknown | 23933819 | Lemke JR , et al. (2013) | |
c.1642G>A | p.Ala548Thr | missense_variant | De novo | NA | Simplex | 23933820 | Lesca G , et al. (2013) | |
c.1954T>G | p.Phe652Val | missense_variant | De novo | NA | Simplex | 23933820 | Lesca G , et al. (2013) | |
c.2081T>C | p.Ile694Thr | missense_variant | De novo | NA | Simplex | 23933820 | Lesca G , et al. (2013) | |
c.2191G>A | p.Asp731Asn | missense_variant | De novo | NA | Simplex | 26544041 | Zhang Y , et al. (2015) | |
c.2332G>C | p.Ala778Pro | missense_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
c.2855A>G | p.Lys952Arg | missense_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
c.2650G>A | p.Asp884Asn | missense_variant | Unknown | - | Unknown | 26637798 | D'Gama AM , et al. (2015) | |
c.3751G>A | p.Asp1251Asn | missense_variant | Familial | Paternal | - | 23933820 | Lesca G , et al. (2013) | |
c.1757G>A | p.Arg586Lys | missense_variant | Familial | Maternal | - | 20890276 | Endele S , et al. (2010) | |
c.2095C>T | p.Pro699Ser | missense_variant | De novo | NA | Simplex | 23933819 | Lemke JR , et al. (2013) | |
c.3120G>C | p.Glu1040Asp | missense_variant | Unknown | - | Unknown | 32277047 | Chevarin M et al. (2020) | |
- | - | copy_number_loss | Familial | Paternal | Multi-generational | 30544257 | Strehlow V , et al. (2018) | |
c.1841A>G | p.Asn614Ser | missense_variant | De novo | NA | - | 28109652 | von Stlpnagel C , et al. (2017) | |
c.1936A>G | p.Thr646Ala | missense_variant | De novo | NA | - | 28109652 | von Stlpnagel C , et al. (2017) | |
c.2007+1G>A | - | splice_site_variant | Familial | Paternal | Simplex | 23933819 | Lemke JR , et al. (2013) | |
c.2007+1G>A | - | splice_site_variant | Familial | Paternal | - | 28109652 | von Stlpnagel C , et al. (2017) | |
c.1306T>C | p.Cys436Arg | missense_variant | De novo | NA | Multiplex | 23933819 | Lemke JR , et al. (2013) | |
c.1592C>T | p.Thr531Met | missense_variant | Familial | Maternal | - | 30544257 | Strehlow V , et al. (2018) | |
c.1692del | p.Met564IlefsTer8 | frameshift_variant | Familial | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.1362del | p.Lys454AsnfsTer11 | frameshift_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.2902G>A | p.Ala968Thr | missense_variant | De novo | NA | Simplex | 22833210 | Tarabeux J , et al. (2011) | |
c.627del | p.Phe210LeufsTer10 | frameshift_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2140del | p.Glu714ArgfsTer7 | frameshift_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2408del | p.Glu803GlyfsTer5 | frameshift_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.3669C>T | p.Thr1223= | synonymous_variant | De novo | NA | Simplex | 22833210 | Tarabeux J , et al. (2011) | |
c.1001T>A | p.Leu334Ter | stop_gained | Familial | Paternal | Multiplex | 23933819 | Lemke JR , et al. (2013) | |
c.2829C>G | p.Tyr943Ter | stop_gained | Familial | Paternal | Multiplex | 23933819 | Lemke JR , et al. (2013) | |
c.2253dup | p.Ser752GlufsTer34 | frameshift_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.551T>G | p.Ile184Ser | missense_variant | Familial | Maternal | Simplex | 23933820 | Lesca G , et al. (2013) | |
c.1946_1947delinsCT | p.Leu649Pro | missense_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.2191G>A | p.Asp731Asn | missense_variant | Familial | Maternal | Simplex | 23933820 | Lesca G , et al. (2013) | |
c.2797G>A | p.Asp933Asn | missense_variant | Familial | Paternal | Simplex | 23933820 | Lesca G , et al. (2013) | |
c.547T>A | p.Phe183Ile | missense_variant | Familial | Paternal | Simplex | 23933819 | Lemke JR , et al. (2013) | |
c.1007+1G>A | - | splice_site_variant | Unknown | Not maternal | Multiplex | 23933819 | Lemke JR , et al. (2013) | |
c.1007+1G>A | p.? | splice_site_variant | Familial | Maternal | Multiplex | 23933819 | Lemke JR , et al. (2013) | |
- | - | translocation | Familial | Maternal & paternal | Multi-generational | 20890276 | Endele S , et al. (2010) | |
c.1007+1G>A | p.? | splice_site_variant | Unknown | - | Multi-generational | 23933819 | Lemke JR , et al. (2013) | |
c.2441T>C | p.Ile814Thr | missense_variant | Familial | Paternal | Simplex | 23933819 | Lemke JR , et al. (2013) | |
c.2449A>G | p.Met817Val | missense_variant | De novo | NA | Simplex | 24903190 | Venkateswaran S , et al. (2014) | |
c.883G>A | p.Gly295Ser | missense_variant | Unknown | Not maternal | Simplex | 23933820 | Lesca G , et al. (2013) | |
c.1447G>A | p.Gly483Arg | missense_variant | Familial | Maternal | Multiplex | 23933820 | Lesca G , et al. (2013) | |
c.1510C>T | p.Arg504Trp | missense_variant | Familial | Maternal | Multiplex | 23933820 | Lesca G , et al. (2013) | |
c.1553G>A | p.Arg518His | missense_variant | Familial | Paternal | Multiplex | 23933820 | Lesca G , et al. (2013) | |
c.692G>A | p.Cys231Tyr | missense_variant | Familial | Maternal | Multiplex | 23933819 | Lemke JR , et al. (2013) | |
c.2113A>G | p.Met705Val | missense_variant | Familial | Maternal | Multiplex | 23933819 | Lemke JR , et al. (2013) | |
c.2200G>C | p.Val734Leu | missense_variant | Familial | Paternal | Multiplex | 23933819 | Lemke JR , et al. (2013) | |
c.2710A>T | p.Ile904Phe | missense_variant | Familial | Paternal | Multiplex | 23933819 | Lemke JR , et al. (2013) | |
c.1686del | p.Phe562LeufsTer2 | frameshift_variant | Familial | Paternal | - | 30544257 | Strehlow V , et al. (2018) | |
c.176_177insAGGC | p.Ala60GlyfsTer79 | frameshift_variant | De novo | NA | - | 30544257 | Strehlow V , et al. (2018) | |
c.1123-2A>G | - | splice_site_variant | Familial | Maternal | Multi-generational | 23933820 | Lesca G , et al. (2013) | |
c.1592C>T | p.Thr531Met | missense_variant | Familial | Maternal | Multiplex | 23933818 | Carvill GL , et al. (2013) | |
c.2T>C | p.Met1? | initiator_codon_variant | Familial | Paternal | Multiplex | 23933818 | Carvill GL , et al. (2013) | |
c.652C>T | p.Gln218Ter | stop_gained | Familial | Maternal | Multi-generational | 20890276 | Endele S , et al. (2010) | |
c.2341_2343delinsAT | p.Gln781IlefsTer27 | frameshift_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.4161C>A | p.Tyr1387Ter | stop_gained | Familial | Maternal | Extended multiplex | 23933820 | Lesca G , et al. (2013) | |
c.2041C>T | p.Arg681Ter | stop_gained | Familial | Maternal | Extended multiplex | 23933819 | Lemke JR , et al. (2013) | |
c.1123-1G>T | - | splice_site_variant | Familial | Maternal | Multi-generational | 30544257 | Strehlow V , et al. (2018) | |
c.2041C>T | p.Arg681Ter | stop_gained | Familial | Paternal | Multi-generational | 30544257 | Strehlow V , et al. (2018) | |
c.236C>G | p.Pro79Arg | missense_variant | Familial | Maternal | Multi-generational | 23933819 | Lemke JR , et al. (2013) | |
c.2146G>A | p.Ala716Thr | missense_variant | Familial | Maternal | Multi-generational | 23933820 | Lesca G , et al. (2013) | |
c.1639_1641del | p.Ser547del | inframe_deletion | Unknown | Not maternal | Multiplex | 23933819 | Lemke JR , et al. (2013) | |
c.1585del | p.Val529TrpfsTer22 | frameshift_variant | Familial | Maternal | Multiplex | 23933819 | Lemke JR , et al. (2013) | |
c.2063G>C | p.Gly688Ala | missense_variant | De novo | NA | Possible multi-generational | 28440294 | Chen XS , et al. (2017) | |
c.2334_2338del | p.Leu779SerfsTer5 | frameshift_variant | Familial | Paternal | Simplex | 23933819 | Lemke JR , et al. (2013) | |
c.1007+1G>A | p.Phe139IlefsTer15 | splice_site_variant | Familial | Paternal | Simplex | 23933818 | Carvill GL , et al. (2013) | |
c.90dup | p.Pro31SerfsTer107 | frameshift_variant | Familial | Maternal | Multi-generational | 23933819 | Lemke JR , et al. (2013) | |
c.1586del | p.Val529GlyfsTer22 | frameshift_variant | Unknown | - | Multi-generational | 28109652 | von Stlpnagel C , et al. (2017) | |
NM_001009184.2:c.445_448delGCGTins69 | p.Ala149SerfsTer8 | frameshift_variant | Unknown | - | - | 30544257 | Strehlow V , et al. (2018) | |
c.1928C>A | p.Ala643Asp | missense_variant | De novo (paternal gonadal mosaicism) | - | Multiplex | 29644724 | Fernndez-Marmiesse A , et al. (2018) | |
c.1007+1G>A | p.Phe139IlefsTer15 | splice_site_variant | Familial | Maternal and paternal | Multi-generational | 23933818 | Carvill GL , et al. (2013) |
Common Variants (5)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.2169-7736A>G;c.2325-7736A>G;c.1698-7736A>G | - | intron_variant | - | - | - | 29483656 | Pardias AF , et al. (2018) | |
c.2168+4735G>T;c.2324+4735G>T;c.1697+4735G>T | A/C | intron_variant | - | - | - | 23453885 | Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) | |
c.2316-35G>C | - | intron_variant | - | - | - | 15830322 | Barnby G , et al. (2005) | |
c.1576T>C | p.(=) | synonymous_variant | - | - | - | 15830322 | Barnby G , et al. (2005) | |
c.*1212C>T;c.*1418C>T | - | 3_prime_UTR_variant | - | - | - | 15830322 | Barnby G , et al. (2005) |
SFARI Gene score
Strong Candidate


Genetic association was observed between the GRIN2A gene and autism in a cohort from the International Molecular Genetics Study of Autism Consortium (IMGSAC) in Barnby et al., 2005. Heterozygous variants in the GRIN2A gene are associated with focal epilepsy and speech disorder (FESD) with or without mental retardation (OMIM 245570), a childhood-onset seizure disorder with a highly variable phenotype. Strehlow et al., 2018 characterized a cohort of 248 individuals with pathogenic and likely pathogenic GRIN2A variants and found that in a subset of 70 cases with available information about neuropsychiatric co-morbidities, autism spectrum disorder was present in 6 cases.
Score Delta: Score remained at 3
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
7/1/2020

Score remained at 3
Description
Genetic association was observed between the GRIN2A gene and autism in a cohort from the International Molecular Genetics Study of Autism Consortium (IMGSAC) in Barnby et al., 2005. Heterozygous variants in the GRIN2A gene are associated with focal epilepsy and speech disorder (FESD) with or without mental retardation (OMIM 245570), a childhood-onset seizure disorder with a highly variable phenotype. Strehlow et al., 2018 characterized a cohort of 248 individuals with pathogenic and likely pathogenic GRIN2A variants and found that in a subset of 70 cases with available information about neuropsychiatric co-morbidities, autism spectrum disorder was present in 6 cases.
Reports Added
[Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression2020] [Clustering by phenotype and genome-wide association study in autism2020] [An Epilepsy-Associated GRIN2A Rare Variant Disrupts CaMKIIñ Phosphorylation of GluN2A and NMDA Receptor Trafficking2020]4/1/2020

Score remained at 3
Description
Genetic association was observed between the GRIN2A gene and autism in a cohort from the International Molecular Genetics Study of Autism Consortium (IMGSAC) in Barnby et al., 2005. Heterozygous variants in the GRIN2A gene are associated with focal epilepsy and speech disorder (FESD) with or without mental retardation (OMIM 245570), a childhood-onset seizure disorder with a highly variable phenotype. Strehlow et al., 2018 characterized a cohort of 248 individuals with pathogenic and likely pathogenic GRIN2A variants and found that in a subset of 70 cases with available information about neuropsychiatric co-morbidities, autism spectrum disorder was present in 6 cases.
1/1/2020

Score remained at 3
Description
Genetic association was observed between the GRIN2A gene and autism in a cohort from the International Molecular Genetics Study of Autism Consortium (IMGSAC) in Barnby et al., 2005. Heterozygous variants in the GRIN2A gene are associated with focal epilepsy and speech disorder (FESD) with or without mental retardation (OMIM 245570), a childhood-onset seizure disorder with a highly variable phenotype. Strehlow et al., 2018 characterized a cohort of 248 individuals with pathogenic and likely pathogenic GRIN2A variants and found that in a subset of 70 cases with available information about neuropsychiatric co-morbidities, autism spectrum disorder was present in 6 cases.
10/1/2019

Decreased from 3 to 2
New Scoring Scheme
Description
Genetic association was observed between the GRIN2A gene and autism in a cohort from the International Molecular Genetics Study of Autism Consortium (IMGSAC) in Barnby et al., 2005. Heterozygous variants in the GRIN2A gene are associated with focal epilepsy and speech disorder (FESD) with or without mental retardation (OMIM 245570), a childhood-onset seizure disorder with a highly variable phenotype. Strehlow et al., 2018 characterized a cohort of 248 individuals with pathogenic and likely pathogenic GRIN2A variants and found that in a subset of 70 cases with available information about neuropsychiatric co-morbidities, autism spectrum disorder was present in 6 cases.
Reports Added
[New Scoring Scheme]7/1/2019

Decreased from 3 to 3
Description
Genetic association was observed between the GRIN2A gene and autism in a cohort from the International Molecular Genetics Study of Autism Consortium (IMGSAC) in Barnby et al., 2005. Heterozygous variants in the GRIN2A gene are associated with focal epilepsy and speech disorder (FESD) with or without mental retardation (OMIM 245570), a childhood-onset seizure disorder with a highly variable phenotype. Strehlow et al., 2018 characterized a cohort of 248 individuals with pathogenic and likely pathogenic GRIN2A variants and found that in a subset of 70 cases with available information about neuropsychiatric co-morbidities, autism spectrum disorder was present in 6 cases.
1/1/2019

Decreased from 4 to 3
Description
Genetic association was observed between the GRIN2A gene and autism in a cohort from the International Molecular Genetics Study of Autism Consortium (IMGSAC) in Barnby et al., 2005. Heterozygous variants in the GRIN2A gene are associated with focal epilepsy and speech disorder (FESD) with or without mental retardation (OMIM 245570), a childhood-onset seizure disorder with a highly variable phenotype. Strehlow et al., 2018 characterized a cohort of 248 individuals with pathogenic and likely pathogenic GRIN2A variants and found that in a subset of 70 cases with available information about neuropsychiatric co-morbidities, autism spectrum disorder was present in 6 cases.
Reports Added
[Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation.2014] [Functional Evaluation of a De Novo GRIN2A Mutation Identified in a Patient with Profound Global Developmental Delay and Refractory Epilepsy.2017] [GRIN2A-related disorders: genotype and functional consequence predict phenotype.2018]4/1/2018

Decreased from 4 to 4.3
Description
4
Reports Added
[Rare loss of function mutations in N-methyl-D-aspartate glutamate receptors and their contributions to schizophrenia susceptibility.2018] [Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.2018] [A novel missense mutation in GRIN2A causes a nonepileptic neurodevelopmental disorder.2018]7/1/2017

Decreased from 4 to 4
Description
There is association and linkage evidence for the GRIN2A gene. For example, genetic association has been found between the GRIN2A gene and autism in an IMGSAC cohort (Barnby et al., 2005).
4/1/2017

Decreased from 4 to 4
Description
There is association and linkage evidence for the GRIN2A gene. For example, genetic association has been found between the GRIN2A gene and autism in an IMGSAC cohort (Barnby et al., 2005).
Reports Added
[Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.2013] [Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia.2011] [Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT.2005] [Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes.2010] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [GRIN2A mutations cause epilepsy-aphasia spectrum disorders.2013] [Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes.2013] [GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction.2013] [Diagnostic exome sequencing in persons with severe intellectual disability.2012] [Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain.1988] [Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.1994] [Integrative properties of radial oblique dendrites in hippocampal CA1 pyramidal neurons.2006] [Cholesterol-enriched diet affects spatial learning and synaptic function in hippocampal synapses.2006] [Zinc modulates bidirectional hippocampal plasticity by effects on NMDA receptors.2006] [NMDA receptor function: subunit composition versus spatial distribution.2006] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.2015] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Mechanistic Insight into NMDA Receptor Dysregulation by Rare Variants in the GluN2A and GluN2B Agonist Binding Domains.2016] [Molecular Mechanism of Disease-Associated Mutations in the Pre-M1 Helix of NMDA Receptors and Potential Rescue Pharmacology.2017] [Epilepsy in patients with GRIN2A alterations: Genetics, neurodevelopment, epileptic phenotype and response to anticonvulsive drugs.2017] [A de novo loss-of-function GRIN2A mutation associated with childhood focal epilepsy and acquired epileptic aphasia.2017] [Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency - molecular profiling and functional rescue.2017] [A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.2017] [Functional assessment of the NMDA receptor variant GluN2A R586K.2017] [Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]1/1/2017

Decreased from 4 to 4
Description
There is association and linkage evidence for the GRIN2A gene. For example, genetic association has been found between the GRIN2A gene and autism in an IMGSAC cohort (Barnby et al., 2005).
Reports Added
[Molecular Mechanism of Disease-Associated Mutations in the Pre-M1 Helix of NMDA Receptors and Potential Rescue Pharmacology.2017] [Epilepsy in patients with GRIN2A alterations: Genetics, neurodevelopment, epileptic phenotype and response to anticonvulsive drugs.2017] [A de novo loss-of-function GRIN2A mutation associated with childhood focal epilepsy and acquired epileptic aphasia.2017] [Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency - molecular profiling and functional rescue.2017]10/1/2016

Decreased from 4 to 4
Description
There is association and linkage evidence for the GRIN2A gene. For example, genetic association has been found between the GRIN2A gene and autism in an IMGSAC cohort (Barnby et al., 2005).
7/1/2016

Decreased from 4 to 4
Description
There is association and linkage evidence for the GRIN2A gene. For example, genetic association has been found between the GRIN2A gene and autism in an IMGSAC cohort (Barnby et al., 2005).
1/1/2016

Decreased from 4 to 4
Description
There is association and linkage evidence for the GRIN2A gene. For example, genetic association has been found between the GRIN2A gene and autism in an IMGSAC cohort (Barnby et al., 2005).
Reports Added
[Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.2013] [Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia.2011] [Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT.2005] [Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes.2010] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [GRIN2A mutations cause epilepsy-aphasia spectrum disorders.2013] [Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes.2013] [GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction.2013] [Diagnostic exome sequencing in persons with severe intellectual disability.2012] [Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain.1988] [Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.1994] [Integrative properties of radial oblique dendrites in hippocampal CA1 pyramidal neurons.2006] [Cholesterol-enriched diet affects spatial learning and synaptic function in hippocampal synapses.2006] [Zinc modulates bidirectional hippocampal plasticity by effects on NMDA receptors.2006] [NMDA receptor function: subunit composition versus spatial distribution.2006] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.2015]7/1/2014

Increased from No data to 4
Description
There is association and linkage evidence for the GRIN2A gene. For example, genetic association has been found between the GRIN2A gene and autism in an IMGSAC cohort (Barnby et al., 2005).
4/1/2014

Increased from No data to 4
Description
There is association and linkage evidence for the GRIN2A gene. For example, genetic association has been found between the GRIN2A gene and autism in an IMGSAC cohort (Barnby et al., 2005).
Krishnan Probability Score
Score 0.63703855943237
Ranking 56/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99804480805101
Ranking 1249/18225 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.94842664598765
Ranking 17679/18665 scored genes
[Show Scoring Methodology]
Larsen Cumulative Evidence Score
Score 9
Ranking 197/461 scored genes
[Show Scoring Methodology]
Zhang D Score
Score -0.085195646077055
Ranking 11774/20870 scored genes
[Show Scoring Methodology]