Evidence map›Paper›PMID 38307912›Full record

ArticleScientific reports2024

Differential functional consequences of GRIN2A mutations associated with schizophrenia and neurodevelopmental disorders.

Nate Shepard, David Baez-Nieto, Sumaiya Iqbal, Erkin Kurganov, Nikita Budnik, Arthur J Campbell, Jen Q Pan, Morgan Sheng, Zohreh Farsi

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
12.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
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  14. Current neuropharmacology · 2025
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  16. Decoding the genetic landscape of autism: A comprehensive review.World journal of clinical pediatrics · 2024
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Nate ShepardStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
David Baez-NietoStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sumaiya IqbalThe Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Erkin KurganovStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nikita BudnikStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Arthur J CampbellStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jen Q PanStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Morgan ShengStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. msheng@broadinstitute.org.
Zohreh FarsiStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. zfarsi@broadinstitute.org.
Broad Institute · USInstitute of Cognitive and Brain Sciences · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human genetic studies have revealed rare missense and protein-truncating variants in GRIN2A, encoding for the GluN2A subunit of the NMDA receptors, that confer significant risk for schizophrenia (SCZ). Mutations in GRIN2A are also associated with epilepsy and developmental delay/intellectual disability (DD/ID). However, it remains enigmatic how alterations to the same protein can result in diverse clinical phenotypes. Here, we performed functional characterization of human GluN1/GluN2A heteromeric NMDA receptors that contain SCZ-linked GluN2A variants, and compared them to NMDA receptors with GluN2A variants associated with epilepsy or DD/ID. Our findings demonstrate that SCZ-associated GRIN2A variants were predominantly loss-of-function (LoF), whereas epilepsy and DD/ID-associated variants resulted in both gain- and loss-of-function phenotypes. We additionally show that M653I and S809R, LoF GRIN2A variants associated with DD/ID, exert a dominant-negative effect when co-expressed with a wild-type GluN2A, whereas E58Ter and Y698C, SCZ-linked LoF variants, and A727T, an epilepsy-linked LoF variant, do not. These data offer a potential mechanism by which SCZ/epilepsy and DD/ID-linked variants can cause different effects on receptor function and therefore result in divergent pathological outcomes.

Indexed as

EpilepsyNeurodevelopmental DisordersSchizophreniaHumansMutationReceptors, N-Methyl-D-AspartateReceptors, N-Methyl-D-Aspartate

Identifiers

PMID38307912
PMCPMC10837427
OpenAlexW4391472857

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.