Human Gene Module / Chromosome 9 / GRIN1

GRIN1Glutamate receptor, ionotropic, N-methyl D-aspartate 1

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
2 / 30
Rare Variants / Common Variants
89 / 0
Aliases
GRIN1, RP11-350O14.1,  GluN1,  MRD8,  NMDA1,  NMDAR1,  NR1
Associated Syndromes
-
Chromosome Band
9q34.3
Associated Disorders
DD/NDD, ID, ASD
Relevance to Autism

Decreased social interaction in GRIN1-knockout mice was observed in two separate studies (Gandal et al., 2012; Saunders et al., 2013).

Molecular Function

The protein encoded by this gene is a critical subunit of N-methyl-D-aspartate receptors, members of the glutamate receptor channel superfamily which are heteromeric protein complexes with multiple subunits arranged to form a ligand-gated ion channel. These subunits play a key role in the plasticity of synapses, which is believed to underlie memory and learning.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to GRIN1 (30 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction Gandal MJ , et al. (2012) No -
2 Recent Recommendation Knockout of NMDA receptors in parvalbumin interneurons recreates autism-like phenotypes Saunders JA , et al. (2013) No -
3 Support De novo mutations in epileptic encephalopathies Epi4K Consortium , et al. (2013) No -
4 Recent Recommendation Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism Moy SS , et al. (2013) No -
5 Support Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing Redin C , et al. (2014) No -
6 Recent Recommendation Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy Lemke JR , et al. (2016) No ASD
7 Support Mutations in HECW2 are associated with intellectual disability and epilepsy Halvardson J , et al. (2016) No -
8 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
9 Support Novel homozygous missense variant of GRIN1 in two sibs with intellectual disability and autistic features without epilepsy Rossi M , et al. (2017) No Stereotypic movements of the midline, hypotonia, a
10 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 -
11 Support GRIN1 mutation associated with intellectual disability alters NMDA receptor trafficking and function Chen W , et al. (2017) No Hypotonia, stereotypic behavior
12 Support De novo GRIN1 mutations: An emerging cause of severe early infantile encephalopathy Zehavi Y , et al. (2017) No Early onset encephalopathy, hypotonia
13 Support Rare loss of function mutations in N-methyl-D-aspartate glutamate receptors and their contributions to schizophrenia susceptibility Yu Y , et al. (2018) No -
14 Support De novo mutations in GRIN1 cause extensive bilateral polymicrogyria Fry AE , et al. (2018) No Autistic features
15 Support The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders Jiao Q , et al. (2019) No DD, ID, autistic behavior
16 Support Abnormal circadian rhythm in patients with GRIN1-related developmental epileptic encephalopathy Scala M , et al. (2019) No Stereotypies
17 Support De novo GRIN variants in NMDA receptor M2 channel pore-forming loop are associated with neurological diseases Li J , et al. (2019) No -
18 Support Control of Long-Term Synaptic Potentiation and Learning by Alternative Splicing of the NMDA Receptor Subunit GluN1 Sengar AS , et al. (2019) Yes -
19 Support - Santos-Gómez A et al. (2021) No Autistic features, stereotypy
20 Support - Brock S et al. (2022) No -
21 Support - brain (Lipi) No -
22 Support - Chen Y et al. (2021) No -
23 Support - Levchenko O et al. (2022) No -
24 Support - Zhou X et al. (2022) Yes -
25 Support - Balasar et al. (2023) No -
26 Support - M Cecilia Poli et al. () No -
27 Support - Marketa Wayhelova et al. (2024) No -
28 Support - Amalia J Napoli et al. (2024) No -
29 Support - Yuchen Xu et al. (2024) No ASD
30 Support - Axel Schmidt et al. (2024) No Cognitive impairment
Rare Variants   (89)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2590-363A>G - intron_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1045G>A p.Ala349Thr missense_variant Unknown - - 29317596 Yu Y , et al. (2018)
c.421G>A p.Val141Met missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.670A>G p.Asn224Asp missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1861G>A p.Ala621Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1906T>G p.Trp636Gly missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2531G>C p.Gly844Ala missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1858G>C p.Asp620His missense_variant De novo - - 28228639 Chen W , et al. (2017)
c.1652T>C p.Leu551Pro missense_variant De novo - - 29365063 Fry AE , et al. (2018)
c.1658C>T p.Pro553Leu missense_variant De novo - - 29365063 Fry AE , et al. (2018)
c.1940A>G p.Tyr647Cys missense_variant De novo - - 29365063 Fry AE , et al. (2018)
c.1949A>T p.Asn650Ile missense_variant De novo - - 29365063 Fry AE , et al. (2018)
c.1958C>G p.Ala653Gly missense_variant De novo - - 29365063 Fry AE , et al. (2018)
c.1975C>T p.Arg659Trp missense_variant De novo - - 29365063 Fry AE , et al. (2018)
c.2021A>T p.Asn674Ile missense_variant De novo - - 29365063 Fry AE , et al. (2018)
c.2365G>A p.Asp789Asn missense_variant De novo - - 29365063 Fry AE , et al. (2018)
c.2381G>A p.Arg794Gln missense_variant De novo - - 29365063 Fry AE , et al. (2018)
c.2530C>T p.Arg844Cys missense_variant De novo - - 30945278 Jiao Q , et al. (2019)
- p.Arg548Trp missense_variant De novo - - 34884460 Santos-Gómez A et al. (2021)
- p.Asp732Glu missense_variant De novo - - 34884460 Santos-Gómez A et al. (2021)
- p.Met818Val missense_variant De novo - - 34884460 Santos-Gómez A et al. (2021)
- p.Pro805Ser missense_variant De novo - - 34884460 Santos-Gómez A et al. (2021)
- p.Ser617Cys missense_variant De novo - - 34884460 Santos-Gómez A et al. (2021)
c.1654A>C p.Lys552Gln missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.1656C>A p.Asp552Glu missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.1670C>G p.Pro557Arg missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.1795G>C p.Asp599His missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.1852G>C p.Glu618Gln missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.1923G>A p.Met641Ile missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.1933G>T p.Ala645Ser missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.1940A>C p.Tyr647Ser missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.1950C>G p.Asn650Lys missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.1984G>A p.Glu662Lys missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.2416G>A p.Ala806Thr missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.2443G>A p.Gly815Arg missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.2444G>T p.Arg815Leu missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.2449T>C p.Phe817Leu missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.2479G>A p.Ala827Thr missense_variant Unknown - - 27164704 Lemke JR , et al. (2016)
c.2530C>T p.Arg844Cys missense_variant De novo - - 27164704 Lemke JR , et al. (2016)
c.2063C>A p.Ser688Tyr missense_variant De novo - - 28389307 Zehavi Y , et al. (2017)
c.2479G>A p.Ala827Thr missense_variant De novo - - 28389307 Zehavi Y , et al. (2017)
c.1852G>C p.Gly618Arg missense_variant Unknown - - 38177409 M Cecilia Poli et al. ()
c.230C>T p.Ser77Leu missense_variant De novo - Simplex 35873028 Chen Y et al. (2021)
c.2272G>A p.Glu758Lys missense_variant De novo - - 27479843 Lelieveld SH et al. (2016)
c.1853G>T p.Gly618Val missense_variant De novo - - 39039281 Axel Schmidt et al. (2024)
c.2530C>T p.Arg844Cys missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1858G>A p.Asp620Asn missense_variant De novo - Simplex 28228639 Chen W , et al. (2017)
c.1658C>T p.Pro553Leu missense_variant De novo - Simplex 35393335 Brock S et al. (2022)
c.1957G>A p.Ala653Thr missense_variant De novo - Simplex 35393335 Brock S et al. (2022)
c.1972G>T p.Ala658Ser missense_variant De novo - Simplex 35393335 Brock S et al. (2022)
c.2231G>A p.Cys744Tyr missense_variant De novo - Simplex 35393335 Brock S et al. (2022)
c.1744C>T p.Arg582Cys missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1733C>G p.Pro578Arg missense_variant De novo - Simplex 25167861 Redin C , et al. (2014)
c.2443G>A p.Gly815Arg missense_variant De novo - Simplex 31176596 Scala M , et al. (2019)
c.2443G>T p.Gly815Trp missense_variant De novo - Simplex 31176596 Scala M , et al. (2019)
c.2356G>A p.Glu786Lys missense_variant Unknown - Simplex 37524782 Balasar et al. (2023)
c.1616_1618dup p.Thr539dup inframe_insertion De novo - - 27164704 Lemke JR , et al. (2016)
c.1910C>T p.Ala637Val missense_variant De novo - Simplex 38538865 Yuchen Xu et al. (2024)
c.1921A>T p.Met641Leu missense_variant De novo - Simplex 38538865 Yuchen Xu et al. (2024)
c.1923G>A p.Met641Ile missense_variant De novo - Simplex 38538865 Yuchen Xu et al. (2024)
c.1949A>T p.Asn650Ile missense_variant De novo - Simplex 38538865 Yuchen Xu et al. (2024)
c.1954G>A p.Ala652Thr missense_variant De novo - Simplex 38538865 Yuchen Xu et al. (2024)
c.1961T>G p.Phe654Cys missense_variant De novo - Simplex 38538865 Yuchen Xu et al. (2024)
c.1964T>A p.Leu655Gln missense_variant De novo - Simplex 38538865 Yuchen Xu et al. (2024)
c.1909G>T p.Ala637Ser missense_variant De novo - Unknown 38538865 Yuchen Xu et al. (2024)
c.1910C>T p.Ala637Val missense_variant De novo - Unknown 38538865 Yuchen Xu et al. (2024)
c.1913G>C p.Gly638Ala missense_variant Unknown - Unknown 38538865 Yuchen Xu et al. (2024)
c.1913G>T p.Gly638Val missense_variant De novo - Unknown 38538865 Yuchen Xu et al. (2024)
c.1921A>G p.Met641Val missense_variant De novo - Unknown 38538865 Yuchen Xu et al. (2024)
c.1923G>A p.Met641Ile missense_variant De novo - Unknown 38538865 Yuchen Xu et al. (2024)
c.1924A>C p.Ile642Leu missense_variant Unknown - Unknown 38538865 Yuchen Xu et al. (2024)
c.1925T>C p.Ile642Thr missense_variant De novo - Unknown 38538865 Yuchen Xu et al. (2024)
c.1927A>G p.Ile643Val missense_variant Unknown - Unknown 38538865 Yuchen Xu et al. (2024)
c.1930G>A p.Val644Met missense_variant Unknown - Unknown 38538865 Yuchen Xu et al. (2024)
c.1940A>C p.Tyr647Ser missense_variant De novo - Unknown 38538865 Yuchen Xu et al. (2024)
- p.Ile619_Gly620dup inframe_insertion De novo - - 34884460 Santos-Gómez A et al. (2021)
c.1858G>A p.Gly620Arg missense_variant De novo - - 34884460 Santos-Gómez A et al. (2021)
c.1921A>G p.Met641Val missense_variant De novo - - 34884460 Santos-Gómez A et al. (2021)
c.2414C>T p.Pro805Leu missense_variant De novo - - 34884460 Santos-Gómez A et al. (2021)
c.2441C>A p.Ala814Asp missense_variant De novo - - 34884460 Santos-Gómez A et al. (2021)
c.2479G>A p.Gly827Arg missense_variant De novo - - 34884460 Santos-Gómez A et al. (2021)
c.2500G>C p.Glu834Gln missense_variant De novo - - 34884460 Santos-Gómez A et al. (2021)
c.1918G>C p.Ala640Pro missense_variant De novo - Simplex 35887114 Levchenko O et al. (2022)
c.1191A>C p.Arg397Ser missense_variant De novo - Simplex 27334371 Halvardson J , et al. (2016)
c.1422C>A p.Tyr474Ter stop_gained Familial Both parents Simplex 35393335 Brock S et al. (2022)
c.2479G>A p.Gly827Arg missense_variant De novo - Simplex 38321498 Marketa Wayhelova et al. (2024)
c.1666C>T p.Gln556Ter stop_gained Familial Both parents Multiplex 27164704 Lemke JR , et al. (2016)
c.679G>C p.Ala227Pro missense_variant Familial Both parents Multiplex 28051072 Rossi M , et al. (2017)
c.649C>T p.Gln217Ter missense_variant Familial Both parents Multiplex 27164704 Lemke JR , et al. (2016)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 Genes

We 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.

1/1/2020
1
icon
1

Score remained at 1

Description

Decreased social interaction in GRIN1-knockout mice was observed in two separate studies (Gandal et al., 2012; Saunders et al., 2013). Mutations in GRIN1 are associated with an autosomal dominant form with intellectual disability (MRD8; OMIM 614254). 7 of 28 individuals with GRIN1 variants in Lemke et al., 2016 had ASD in addition to intellectual disability with or without epilepsy; this included a homozygous partial loss-of-function GRIN1 missense variant in two siblings with ASD and ID from a consanguineous family, as well as two de novo loss-of-function missense variants in patients with ASD and severe ID.

Reports Added
[Control of Long-Term Synaptic Potentiation and Learning by Alternative Splicing of the NMDA Receptor Subunit GluN1.2019]
10/1/2019
3
icon
1

Decreased from 3 to 1

New Scoring Scheme
Description

Decreased social interaction in GRIN1-knockout mice was observed in two separate studies (Gandal et al., 2012; Saunders et al., 2013). Mutations in GRIN1 are associated with an autosomal dominant form with intellectual disability (MRD8; OMIM 614254). 7 of 28 individuals with GRIN1 variants in Lemke et al., 2016 had ASD in addition to intellectual disability with or without epilepsy; this included a homozygous partial loss-of-function GRIN1 missense variant in two siblings with ASD and ID from a consanguineous family, as well as two de novo loss-of-function missense variants in patients with ASD and severe ID.

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

Decreased social interaction in GRIN1-knockout mice was observed in two separate studies (Gandal et al., 2012; Saunders et al., 2013). Mutations in GRIN1 are associated with an autosomal dominant form with intellectual disability (MRD8; OMIM 614254). 7 of 28 individuals with GRIN1 variants in Lemke et al., 2016 had ASD in addition to intellectual disability with or without epilepsy; this included a homozygous partial loss-of-function GRIN1 missense variant in two siblings with ASD and ID from a consanguineous family, as well as two de novo loss-of-function missense variants in patients with ASD and severe ID.

Reports Added
[Abnormal circadian rhythm in patients with GRIN1-related developmental epileptic encephalopathy.2019] [De novo GRIN variants in NMDA receptor M2 channel pore-forming loop are associated with neurological diseases.2019]
4/1/2019
3
icon
3

Decreased from 3 to 3

Description

Decreased social interaction in GRIN1-knockout mice was observed in two separate studies (Gandal et al., 2012; Saunders et al., 2013). Mutations in GRIN1 are associated with an autosomal dominant form with intellectual disability (MRD8; OMIM 614254). 7 of 28 individuals with GRIN1 variants in Lemke et al., 2016 had ASD in addition to intellectual disability with or without epilepsy; this included a homozygous partial loss-of-function GRIN1 missense variant in two siblings with ASD and ID from a consanguineous family, as well as two de novo loss-of-function missense variants in patients with ASD and severe ID.

Reports Added
[The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders.2019]
4/1/2017
3
icon
3

Decreased from 3 to 3

Description

Decreased social interaction in GRIN1-knockout mice was observed in two separate studies (Gandal et al., 2012; Saunders et al., 2013). Mutations in GRIN1 are associated with an autosomal dominant form with intellectual disability (MRD8; OMIM 614254). 7 of 28 individuals with GRIN1 variants in Lemke et al., 2016 had ASD in addition to intellectual disability with or without epilepsy; this included a homozygous partial loss-of-function GRIN1 missense variant in two siblings with ASD and ID from a consanguineous family, as well as two de novo loss-of-function missense variants in patients with ASD and severe ID.

Reports Added
[De novo mutations in epileptic encephalopathies.2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction.2012] [Knockout of NMDA receptors in parvalbumin interneurons recreates autism-like phenotypes.2013] [Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism.2013] [Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy.2016] [Mutations in HECW2 are associated with intellectual disability and epilepsy.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Novel homozygous missense variant of GRIN1 in two sibs with intellectual disability and autistic features without epilepsy.2017] [Molecular Mechanism of Disease-Associated Mutations in the Pre-M1 Helix of NMDA Receptors and Potential Rescue Pharmacology.2017] [GRIN1 mutation associated with intellectual disability alters NMDA receptor trafficking and function.2017] [De novo GRIN1 mutations: An emerging cause of severe early infantile encephalopathy.2017]
1/1/2017
3
icon
3

Decreased from 3 to 3

Description

Decreased social interaction in GRIN1-knockout mice was observed in two separate studies (Gandal et al., 2012; Saunders et al., 2013). Mutations in GRIN1 are associated with an autosomal dominant form with intellectual disability (MRD8; OMIM 614254). 7 of 28 individuals with GRIN1 variants in Lemke et al., 2016 had ASD in addition to intellectual disability with or without epilepsy; this included a homozygous partial loss-of-function GRIN1 missense variant in two siblings with ASD and ID from a consanguineous family, as well as two de novo loss-of-function missense variants in patients with ASD and severe ID.

Reports Added
[Novel homozygous missense variant of GRIN1 in two sibs with intellectual disability and autistic features without epilepsy.2017] [Molecular Mechanism of Disease-Associated Mutations in the Pre-M1 Helix of NMDA Receptors and Potential Rescue Pharmacology.2017] [GRIN1 mutation associated with intellectual disability alters NMDA receptor trafficking and function.2017]
7/1/2016
3
icon
3

Decreased from 3 to 3

Description

Decreased social interaction in GRIN1-knockout mice was observed in two separate studies (Gandal et al., 2012; Saunders et al., 2013). Mutations in GRIN1 are associated with an autosomal dominant form with intellectual disability (MRD8; OMIM 614254). 7 of 28 individuals with GRIN1 variants in Lemke et al., 2016 had ASD in addition to intellectual disability with or without epilepsy; this included a homozygous partial loss-of-function GRIN1 missense variant in two siblings with ASD and ID from a consanguineous family, as well as two de novo loss-of-function missense variants in patients with ASD and severe ID.

Reports Added
[Mutations in HECW2 are associated with intellectual disability and epilepsy.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016]
4/1/2016
5
icon
3

Decreased from 5 to 3

Description

Decreased social interaction in GRIN1-knockout mice was observed in two separate studies (Gandal et al., 2012; Saunders et al., 2013). Mutations in GRIN1 are associated with an autosomal dominant form with intellectual disability (MRD8; OMIM 614254). 7 of 28 individuals with GRIN1 variants in Lemke et al., 2016 had ASD in addition to intellectual disability with or without epilepsy; this included a homozygous partial loss-of-function GRIN1 missense variant in two siblings with ASD and ID from a consanguineous family, as well as two de novo loss-of-function missense variants in patients with ASD and severe ID.

Reports Added
[De novo mutations in epileptic encephalopathies.2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction.2012] [Knockout of NMDA receptors in parvalbumin interneurons recreates autism-like phenotypes.2013] [Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism.2013] [Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy.2016]
7/1/2015
icon
5

Increased from to 5

Description

Decreased social interaction in GRIN1-knockout mice was observed in two separate studies (Gandal et al., 2012; Saunders et al., 2013). Mutations in GRIN1 are associated with an autosomal dominant form with intellectual disability (MRD8; OMIM 614254).

Krishnan Probability Score

Score 0.61251149887656

Ranking 167/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.97270894606804

Ranking 2310/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.9446230042452

Ranking 16148/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.38612792655463

Ranking 1609/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
Submit New Gene

Report an Error