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Intellectual disability

Gene: GRIA1

Green List (high evidence)
GRIA1 (glutamate ionotropic receptor AMPA type subunit 1)
EnsemblGeneIds (GRCh38): ENSG00000155511
EnsemblGeneIds (GRCh37): ENSG00000155511
OMIM: 138248, Gene2Phenotype
GRIA1 is in 2 panels

7 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence (6 unrelated cases with monoallelic inheritance and functional evidence including Xenopus models) for this gene to be promoted to GREEN at the next major review.
Created: 20 Apr 2023, 10:34 a.m. | Last Modified: 20 Apr 2023, 10:34 a.m.
Panel Version: 5.67
Comment on mode of inheritance: The MOI should be monoallelic, as there is only one case identified with biallelic inheritance.
Created: 20 Apr 2023, 10:31 a.m. | Last Modified: 20 Apr 2023, 10:31 a.m.
Panel Version: 5.63
Four different heterozygous variants in GRIA1 (p.Ala636Thr, p.Gly745Asp, p.Ile627Thr & p.Arg345Gln) have been identified in six unrelated individuals and they were all reported with intellectual disability, moderate to severe cognitive impairment, delayed motor development, speech impairment and behavioural issues such as anxiety, autism spectrum disorder and attention deficit hyperactivity disorder.

Homozygous variant (p.Arg377Ter) has been identified in one individual, who presented with intellectual disability, severe cognitive impairment, delayed motor development, speech impairment (non-verbal) and self-injurious behaviour.

In vitro functional studies with major GluA1-containing AMPAR subtypes carrying the GRIA1 variant mutations showed that three of the four missense variants profoundly perturb receptor function. The homozygous stop-gain variant completely destroyed the expression of GluA1-containing AMPARs. The Xenopus gria1 models also show transient motor deficits, an intermittent seizure phenotype, and a significant impairment to working memory in mutants.

This gene has also been associated with relevant phenotypes in both OMIM (MIM #619927 & MIM #619931) and Gene2Phenotype (with 'moderate' rating).
Created: 20 Apr 2023, 10:23 a.m. | Last Modified: 20 Apr 2023, 10:49 a.m.
Panel Version: 5.67

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

Publications

Created: 20 Apr 2023, 10:23 a.m.
Last Modified: 20 Apr 2023, 10:49 a.m.
Panel version: 5.61

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.
Panel Version: 5.286
Comment on list classification: Maintaining Amber rating as no new evidence has been published since previous review. Most commonly reported as a candidate gene in large screening studies with limited segregation/phenotype/functional data. Also variable penetrance of the ID phenotype. Therefore, there is currently not enough evidence to classify as Green.
Created: 23 Dec 2020, 12:02 p.m. | Last Modified: 23 Dec 2020, 12:02 p.m.
Panel Version: 3.678

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Created: 23 Dec 2020, 12:02 p.m.
Last Modified: 23 Dec 2020, 12:02 p.m.
Panel version: 5.286

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Difficult when novel genes are reported in large cohorts where multiple novel candidates are being put forward and additional phenotypic/segregation information is limited; however, note that three of the four studies are described as moderate-severe or severe ID cohorts.
Created: 6 Feb 2020, 10:43 p.m. | Last Modified: 6 Feb 2020, 10:43 p.m.
Panel Version: 3.0

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice

Created: 6 Feb 2020, 10:43 p.m.
Last Modified: 6 Feb 2020, 10:43 p.m.
Panel version: 3.0

Helen Brittain (Genomics England Curator)

Comment on list classification: Phenotype perhaps too mild in reported cases. Further evidence would assist.
Created: 8 Mar 2018, 1:35 p.m.
Created: 8 Mar 2018, 1:35 p.m.

Panel version: Imported from Intellectual disability update Jan 2018 panel version 0.441

Sarah Leigh (Genomics England Curator)

Comment on mode of pathogenicity: Single pathogenic GOF variant identified p.(A636T)
Created: 6 Mar 2018, 6:15 p.m.
Not associated with phenotype in OMIM or G2P. Single gof variant reported in at least 6 unrelated cases all with autistic syndrome disorder and 4 with features of ID. The variants appear to be de novo in two cases. Supporting functional studies provided in PMID 28628100.
Reported as De novo variant in severe ID case (de Ligt 2012 PMID 23033978) and as a candidate ID gene (Grozeva 2015 PMID 26350204, Gilessen 2014 PMID 24896178)
Created: 6 Mar 2018, 5:24 p.m.
Created: 6 Mar 2018, 5:24 p.m.

Panel version: Imported from Intellectual disability update Jan 2018 panel version 0.370

Caroline Wright (Sanger)

Red List (low evidence)

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Lu Raymond (university of cambridge )

Red List (low evidence)

Created: 23 Feb 2016, 11:34 a.m.

Panel version: 0.306

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Intellectual developmental disorder, autosomal dominant 67, OMIM:619927
  • ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Tags
watchlist_moi
OMIM
138248
Clinvar variants
Variants in GRIA1
Penetrance
Complete
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

11 Oct 2023, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist_moi tag was added to gene: GRIA1.

11 Oct 2023, Gel status: 3

Removed Tag, Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Autism Spectrum Disorder was removed from gene: GRIA1. Tag Q2_23_promote_green was removed from gene: GRIA1.

11 Oct 2023, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to GRIA1. Source Expert Review Green was added to GRIA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

20 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: gria1 has been classified as Amber List (Moderate Evidence).

20 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: gria1 has been classified as Amber List (Moderate Evidence).

20 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: gria1 has been classified as Amber List (Moderate Evidence).

20 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: gria1 has been classified as Amber List (Moderate Evidence).

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set mode of inheritance

Achchuthan Shanmugasundram (Genomics England Curator)

Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Apr 2023, Gel status: 2

Set mode of inheritance

Achchuthan Shanmugasundram (Genomics England Curator)

Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Apr 2023, Gel status: 2

Set mode of inheritance

Achchuthan Shanmugasundram (Genomics England Curator)

Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Apr 2023, Gel status: 2

Removed Tag, Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag watchlist was removed from gene: GRIA1. Tag Q2_23_promote_green tag was added to gene: GRIA1.

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825

20 Apr 2023, Gel status: 2

Set mode of inheritance

Achchuthan Shanmugasundram (Genomics England Curator)

Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GRIA1 were changed from Intellectual disability to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931

20 Apr 2023, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825

20 Apr 2023, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825

20 Apr 2023, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825

20 Apr 2023, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825

20 Apr 2023, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178

23 Dec 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: gria1 has been classified as Amber List (Moderate Evidence).

14 Mar 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for GRIA1 were set to Intellectual disability

12 Mar 2018, Gel status: 2

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

12 Mar 2018, Gel status: 2

Set mode of pathogenicity

Ellen McDonagh (Genomics England Curator)

Mode of pathogenicity for GRIA1 was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

12 Mar 2018, Gel status: 2

Added New Source, Set mode of inheritance, Set publications

Ellen McDonagh (Genomics England Curator)

Expert Review Amber was added to GRIA1. Panel: Intellectual disability Model of inheritance for gene GRIA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene GRIA1 was set to ['28628100', '23033978', '26350204', '24896178']

13 Nov 2015, Gel status: 1

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

GRIA1 was added to Intellectual disabilitypanel. Sources: Expert Review Red

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

GRIA1 was created by ellenmcdonagh