Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes.
The main results reproduced: recomputed values matched the published ones within tolerance.
A 0–100 reproducibility-quality score from the per-question grades, shown as a z-score: standard deviations above (+) or below (−) the mean of comparable assessments.
▸Reproduction agent’s raw note
Endele et al. 2010 (Nat Genet 42:1021-1026, PMID 20890276) is a candidate-gene clinical-genetics paper: mutation discovery by Sanger sequencing of GRIN2A/GRIN2B + one array-CGH microdeletion, with mechanism shown by two-electrode voltage-clamp electrophysiology. It deposits NO high-throughput dataset and ships NO code, so the bulk is out of scope (wet-lab/clinical). The single reproducible computational layer -- deterministic re-annotation of the 6 reported variants against canonical RefSeq CDS, plus ortholog conservation of the two missense residues -- was reproduced on a «our HPC» compute node (n093): 6/6 variant consequences match exactly (p.Asn615Lys, p.Gln218Ter, p.Arg682Cys, p.Thr268fs, c.411+1 donor, c.2360-2 acceptor), and GluN2A N615 / GluN2B R682 are each conserved 3/3 across human/mouse/rat orthologs. NOT attempted (out of scope, no shipped data/code): Sanger variant discovery in 468+127 individuals, array-CGH, electrophysiology, clinical phenotyping/segregation/trio analysis. Verdict is provisional and must be human-audited.
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Assessment versions
Every reproduction run is kept as an immutable version — anchored to the data as it stood, with a tamper-evident chain hash. A rerun (e.g. after an author updates a deposit) adds a new version; the previous one stays on record.
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v1 current initial assessment Score 96assessed: 2026-06-22 ⛓ 9107ab07f0f6
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Provenance — full disclosure
When this reproduction was carried out, which methodology version was used, and by whom — so the record can be audited and checked independently.
- Reproduced
- 2026-06-22
- Rubric version
- not recorded
- Assessed by
- —
- Last updated
- 2026-08-05
Provisional, curator- or AI-assessed, and independently checkable. A reproduction outcome states what one attempt could reproduce — not a judgement of the authors.
What was reproduced
The exact results taken into scope, with each reported value next to the value our attempt produced.
Scope — PMID 20890276 (Endele et al. 2010, Nature Genetics 42:1021–1026)
Title: Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. DOI: 10.1038/ng.677
Nature of the study
A 2010 candidate-gene / clinical-molecular-genetics paper. Mutation discovery was done by Sanger sequencing of GRIN2A/GRIN2B in patient cohorts plus array-CGH for one microdeletion; mechanism was established by two-electrode voltage-clamp electrophysiology of mutant NMDA receptors. There is no deposited high-throughput dataset (no GEO/SRA/ENA/dbGaP/ArrayExpress accession), no code repository, and no software/pipeline released. The reported variants are now in ClinVar (citing this PMID).
In scope (pipeline-derived / deterministic computational, REPRODUCED)
| # | Result | Method | Status |
|---|---|---|---|
| C1 | Molecular consequence (protein change) of each of the 6 reported GRIN2A/GRIN2B variants | Deterministic re-annotation of reported cDNA changes against canonical RefSeq CDS (NM_001134407.3, NM_000834.5) — a third-party reference applied to the paper's variant calls | reproduced (6/6 exact) |
| C2 | The affected missense residues (GluN2A Asn615 "N-site" in M2; GluN2B Arg682) lie at evolutionarily conserved positions | Motif-anchored ortholog residue conservation across RefSeq proteins | reproduced (qualitative) |
Out of scope (wet-lab / not pipeline-derived / no shipped data — NOT attempted)
- Variant discovery itself — Sanger sequencing of 468 individuals with ID (GRIN2B) and 127 with idiopathic epilepsy/ID (GRIN2A). Raw chromatograms/reads not deposited.
- Array-CGH detection of the GRIN2B-region microdeletion — array data not deposited.
- Electrophysiology — loss of Mg²⁺ block and reduced Ca²⁺ permeability of mutant receptors (e.g. GluN2A N615K). These are wet-lab functional measurements; not reproducible without re-doing the experiment.
- Clinical phenotyping, segregation (three-generation GRIN2A family), de-novo confirmation by trio analysis — manual/clinical.
Why no «our HPC» heavy compute
Nothing in scope requires a compute node: the in-scope results are tiny deterministic
annotation/conservation checks over a handful of reference sequences. «our HPC»
reachability was confirmed («host», user «user») but submitting a SLURM job
would waste a node on a non-pipeline paper. Recorded honestly in qc_room
(compute_ran=false, with rationale).
Assessments & scoring basis
Each contributor’s verdict, the per-question basis, and the auditable, itemised worksheet behind it.
Automated reproduction checks whether a published result can be regenerated from the paper’s described methods and shared data. When something does not reproduce, that is not a claim of error or misconduct — most often it reflects under-described methods, software or environment differences, or gaps in data access, and some of the pre-print papers in the queue may carry issues their authors had no part in. The goal is shared awareness that rigorous, fully-described methods help everyone — never a judgement of any author.
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Reproduction footprint
claude-opus-4-8Measured resources invested to assess this paper — sanitised (machine class only, no job ids/paths). Compute = HPC accounting (SLURM); tokens = the AI agent's session.