Evidence map›Paper›PMID 40546018›Full record

ArticleGenetics2025

Revealing function-altering MECP2 mutations in individuals with autism spectrum disorder using yeast and Drosophila.

Eric Chen, Jessica Schmitt, Graeme McIntosh, Barry P Young, Tianshun Lian, Jie Liu, Kexin K Chen, J Beatrice Liston, Lily MacDonald, Bill Wang and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

19 authors.

Eric ChenDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Jessica SchmittDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Graeme McIntoshDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Barry P YoungDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Tianshun LianDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Jie LiuDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Kexin K ChenDepartment of Psychiatry and Michael Smith Labs, The Michael Smith Institute, The University of British Columbia, 301-2185 East Mall, Vancouver, BC, Canada, V6T 1Z4.ORCID 0009-0008-7657-2482
J Beatrice ListonDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Lily MacDonaldDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Bill WangDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.ORCID 0009-0002-4602-0915
Sonia Medina GiroDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Benjamin BoehmeDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Mriga DasDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Seevasant IndranDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Jesse T ChaoDepartment of Medical Biophysics, Sunnybrook Research Institute, The University of Toronto, 2075 Bayview Avenue, E240, Toronto, ON, Canada, M4N 3M5.ORCID 0000-0002-6995-9581
Sanja RogicDepartment of Psychiatry and Michael Smith Labs, The Michael Smith Institute, The University of British Columbia, 301-2185 East Mall, Vancouver, BC, Canada, V6T 1Z4.
Paul PavlidisDepartment of Psychiatry and Michael Smith Labs, The Michael Smith Institute, The University of British Columbia, 301-2185 East Mall, Vancouver, BC, Canada, V6T 1Z4.ORCID 0000-0002-0426-5028
Douglas W AllanDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.ORCID 0000-0002-3488-8365
Christopher J R LoewenDepartment of Cellular and Physiological Sciences, The Life Sciences Institute, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.ORCID 0000-0002-1760-5749

Funding

Resource Component: Acquisition, maintenance and distribution of Drosophila stocksP40OD018537 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI Annette L. Parks · 2014 to 2026
$13.5M
DROSOPHILA GENOMICS RESOURCE CENTERP40OD010949 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI Andrew Zelhof · 2012 to 2026
$9.4M
NIH HHS P40 OD010949NIH HHS P40 OD018537Simons Foundation Autism Research Initiative
6 · The paper itself

Abstract

Pathogenic variants in MECP2 commonly lead to Rett syndrome, where MECP2's function as a DNA cytosine methylation reader is believed critical. MECP2 variants are also cataloged in individuals with autism spectrum disorder (ASD), including nine missense variants which had no known clinical significance at the start of this study. To assess these nine variants as risk alleles for ASD, we developed MECP2 variant functional assays using budding yeast and Drosophila. We calibrated these assays with known pathogenic and benign variants. Our data predict that four ASD variants are loss of function and five are functional. Protein destabilization offers insight into the altered function of some of these variants. Notably, yeast and Drosophila lack DNA methylation, yet all Rett pathogenic and ASD variants located in the methyl DNA-binding domain that we analyzed proved to be loss of function, suggesting a clinically relevant role for non-methyl DNA-binding by MECP2.

Indexed as

Autism Spectrum DisorderMethyl-CpG-Binding Protein 2AnimalsDNA MethylationDrosophilaDrosophila melanogasterHumansMutationSaccharomyces cerevisiaeMECP2 protein, humanMethyl-CpG-Binding Protein 2ASDautism spectrum disorderbudding yeastDrosophilagenetic interactionsMECP2Rett syndromesentinel interaction mappingtransgenesisvariant predictionVariCarta

Identifiers

PMID40546018
PMCPMC12405999

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.