GRIN Portal v1.0

Welcome to the interactive website for families, clinicians, and researchers dedicated to comprehending GRIN-related disorders

Individuals
Functionally tested variants
Phenotypes (HPOs)

Latest news for the community

  • Access the latest GRIN related publications here.

Interested in other Genes?

Visit also our other Gene Portals!

What is new in version 1.0?

  • The general appearance was updated.
  • Variant analysis shows an ACMG criteria-based variant classification.
  • Variant analysis now allows ACMG criteria customization.
  • A report can now be downloaded in the Variant analysis tab.

History of GRIN research

First description of de novo variants in individuals with intellectual disability
Hamdan et al.
Delineation of the phenotype
Ohba et al.
Delineation of the phenotype
Lemke et al.
First report of cases with brain malformations
Fry et al.
First Report on memantine treatment in a gain-of-function case
Xu et al.

GRIN1-related disorders

GRIN1-related disorder is characterized by mild-to-profound developmental delay / intellectual disability in all affected individuals. Other common manifestations are epilepsy, muscular hypotonia, movement disorders, spasticity, feeding difficulties, and behavior problems. A subset of individuals shows a malformation of cortical development consisting of extensive and diffuse bilateral polymicrogyria. More details can be found on GeneReviews.

Clinical information from the GRIN registry

GRIN1 Phenotypes

Developmental Delay / Intellectual Disability

Abbreviations: DD/ID, Developmental Delay / Intellectual Disability

Seizures

Age at seizure onset

Movement disorder

Cerebral visual impairment

Malformation of cortical development

History of GRIN2A research

First description of de novo variants in individuals with intellectual disability
Endele et al.
Delineation of the phenotype
First report on treatment with memantine in a Gain-of-Function case
Pierson et al.
Delineation of the speech phenotype
Turner et al.
Comprehensive genotype-phenotype correlation
Strehlow et al.
First report on L-Serine treatment in cases with null variants
Krey et al.
First report of recessive inheritance in cases with null variants
Strehlow et al.

GRIN2A-related disorders

GRIN2A-related disorder is characterized by either mild-to-profound developmental delay / intellectual disability in two thirds of affected individuals. Other common manifestations are speech disorders, epilepsy, muscular hypotonia, movement disorders, spasticity, feeding difficulties, and behavior problems. More details can be found on GeneReviews.

Clinical information from the GRIN registry

GRIN2A Phenotypes

Developmental Delay / Intellectual Disability

Abbreviations: DD/ID, Developmental Delay / Intellectual Disability

Seizures

Age at seizure onset

Age at seizure offset

Movement disorder

Further phenotypes

History of GRIN2B research

First description of de novo variants in individuals with intellectual disability
Endele et al.
Delineation of the phenotype
Lemke et al.
Delineation of the phenotype, first report of cases with brain malformations, first report on treatment with memantine in GoF cases
Platzer et al.
First report on L-Serine treatment in a Loss-of-Function case
Soto et al.
First report on L-Serine treatment in cases with null variants
Krey et al.

GRIN2B-related disorders

GRIN2B-related disorder is characterized by mild-to-profound developmental delay / intellectual disability in all affected individuals. Other common manifestations are epilepsy, muscular hypotonia, movement disorders, spasticity, feeding difficulties, and behavior problems. A subset of individuals shows a malformation of cortical development consisting of extensive and diffuse bilateral polymicrogyria. More details can be found on GeneReviews.

Clinical information from the GRIN registry

GRIN2B Phenotypes

Developmental Delay / Intellectual Disability

Abbreviations: DD/ID, Developmental Delay / Intellectual Disability

Seizures

Age at seizure onset

Movement Disorder

Further Phenotypes

History of GRIN2D research

First description of de novo variants with epileptic encephalopathy, first report on treatment with memantine, ketamine, and magnesium in GoF cases
Li et al.
Delineation of the phenotype
XiangWei et al.

GRIN2D-related disorders

GRIN2D-related disorder is characterized by moderate-to-profound developmental delay / intellectual disability in all affected individuals. Other common manifestations are epilepsy, muscular hypotonia, movement disorders, spasticity, feeding difficulties, and behavior problems.

More details can be found on Gene Reviews.

Clinical information from the GRIN registry

GRIN2D Phenotypes

Developmental Delay / Intellectual Disability

Abbreviations: DD/ID, Developmental Delay / Intellectual Disability

Seizures

Age at seizure onset

Movement Disorder

Further Phenotypes

What are GRIN-related disorders?

Expert curated subtitles available in English, German, Danish, Greek, Russian, Spanish, Italian, Ukrainian, and Romanian.

If your family has received a diagnosis of GRIN-related disorders, you've probably never heard of it before. That's okay. Your doctors probably haven't either! But the GRIN Portal community is here to help.

This 6-minute What are GRIN-related disorders? video helps families learn about these disorders in plain language. You'll learn:

- Scientific terms (such as genes, proteins, and variants/mutations) that will help you understand GRIN-related disorders
- What causes GRIN-related disorders
- How GRIN-related disorders are diagnosed
- The symptoms of GRIN-related disorders

Thank you to all contributors!

International

Related organizations

Italy

Austria

Germany

Spain

Brasil

The Netherlands



...and many more! Please contact us if you would like your organization to be listed here.

How to analyse your variant

Loading...
Discover how to customize variant classifications by exploring our tutorial.
Filtered Subset

Variant location


Transcripts: GRIN1: NM_007327.4, GRIN2A: NM_001134407.3, GRIN2B: NM_000834.5, GRIN2D: NM_000836.4


UniProt GRIN1: Q05586

UniProt GRIN2A: Q12879



UniProt GRIN2B: Q13224


UniProt GRIN2D: O15399
Filtered Subset

Number of variants with phenotypic data per domain

Degree of the intellectual disability (ID)

Proportion of individuals with seizures

Filtered Subset







Functional data represent fold changes in receptor activity by gene variant compared to wild-type. Zero means no change from wild-type. Logarithmic scaling was used for the plot. Fold changes below 0.02 are displayed as 0.02. Fold changes >50 are displayed as 50.





All data from the literature and:


Disclaimer: The functional data on this website is provided for academic and research purposes only. It has not undergone clinical validation, and should not be used for medical advice, diagnosis, or treatment.

If you are from Europe, Asia, Africa or other

This chapter of the study is led by geneticist Dr. Johannes Lemke (University of Leipzig). Please fill out the online consent form and continue with the online clinical questionnaire; you can ask your doctor to help fill it out. Please keep your return code and return link to re-access your entry at a later time. The Leipzig team will contact CFERV to conduct functional studies for novel variants entered in the registry. In case we have questions on your entry, you may be contacted by an administrator. In case you have questions, please contact GRIN@medizin.uni-leipzig.de .


Info

Both chapters of the registry will be merged, and patients only need to be enrolled at Colorado or Leipzig. If you have already enrolled but have additional novel information, please get in contact and update your entry.

If you are from North or South America or Australia

1. Email grinresearch@cuanschutz.edu your de-identified genetic testing results to make sure you qualify (and any other questions too!).
2. After we review your genetic testing results, the research coordinator will send you a consent form; sign and return to them. This may take 1-2 weeks.
3. The coordinator will send you the clinical questionnaire. We are updating the questionnaire and want you to fill out the latest version, even if you've already done it before.
4. Fill out the questionnaire; you can ask your doctor to help fill it out.
5. Return the filled-out questionnaire to the coordinator; they will contact CFERV to conduct functional studies for novel variants. Functional analysis takes several months. Your clinician can contact us at grinresearch@cuanschutz.edu to review your results or to discuss medical management. We cannot discuss medical management with you directly.
6. In the near future, we will email you for yearly updates. If you haven't heard from us, then please contact us again. Thank you for participating!!!!

Portal version 1.1

The GRIN Portal is a coalition of investigators seeking to aggregate and harmonize data generated to study GRIN-related disorders, and to make summary data interactively accessible for the wider scientific community, while providing educational resources for everyone. The goals of this project are:

  • Providing information on GRIN-related disorders
  • Supporting research on GRIN-related disorders
  • Facilitating recruitment of individuals to the global GRIN registries

  • Providing support in variant interpretation and classification
  • Visualizing data from the global GRIN registries
  • Linking researchers, clinicians and families

The project is overseen by Johannes Lemke (contact PI), Steve Traynelis (contact PI), Tim Benke and Dennis Lal. This GRIN Portal is an ongoing project and interested collaborators are invited to reach out to join the project. For more information about ongoing projects see here .
The current version of the GRIN Portal has been developed by an international team of researchers and clinicians:

Team Leaders

Johannes Lemke (Leipzig, Germany): General concept, clinical & genetic data

Tim Benke (Denver, US): Clinical & genetic data

Steve Traynelis (Atlanta, US): Molecular data

Dennis Lal (Cleveland, US): General concept, web development, bioinformatics, video production

Clinical & Genetic Data

Ilona Krey

Jenifer Sargent

Chiara Klöckner

Vincent Strehlow

Konrad Platzer

Molecular Data

Scott Myers

Hongjie Yuan

Animal Data

Amy Ramsey

Web Development

Arthur Stefanski

Chiara Klöckner

Tobias Brünger

Marie Mcnee

Tobias Brünger

Eduardo Perez-Palma

Bioinformatics

Chiara Klöckner

Tobias Brünger

Eduardo Perez-Palma

Marie Mcnee

Patrick May

Video

Arthur Stefanski

Arthur Stefanski

Chiara Klöckner

Tobias Brünger

Marie Mcnee

Past Updates

- v0.4 (01/08/2023) Update of clinical and functional dataset, literature references, family organizations, comparison of multiple subsets
- v0.3 (12/04/2022) Layout changes
- v0.2 (25/11/2021) Fixed minor bugs, updated clinical dataset, added variant report download and assessment of multiple variants, added pathogenic variant enriched regions and intolerant microdomains, added multiple family oganizations
- v0.1 (02/06/2021) Public release

Imprint

We object to any commercial use and disclosure of data.

Copyright and use: The authors grants you the right of use to make a private copy for personal purposes. However, you are not entitled to change and/or pass on the materials or publish them yourself. Upon request, you will receive free information about the personal data stored about you. To do so, please contact the administrator.

No liability: The contents of this web project have been carefully checked and created to the best of our knowledge. However, the curation and incorporation of the data presented here is an ongoing process and may not be complete or accurate. No responsibility can be accepted for any damage caused by reliance on or use of the contents of this website.

Terms of Use

All data here are publicly for the benefit of the wider biomedical community. You can freely explore the data, and we encourage the use and publication of results generated from these data. However, we encourage you to contact us before embarking on analyses to check if your proposed analysis overlaps with our team's current work. Further, we request that you actively acknowledge and give attribution to the GRIN Portal project and link back to the relevant page, wherever possible. All users of our data agree not to attempt to reidentify participants. Our data set has been subjected to extensive quality control but may be imperfect so that errors may remain.
If you spot any results that seem impossible or have suggestions for GRIN Portal improvements: contact us so that we can improve.

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