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Record W2682847713 · doi:10.1002/humu.23282

Heterozygous variants in<i>ACTL6A</i>, encoding a component of the BAF complex, are associated with intellectual disability

2017· article· en· W2682847713 on OpenAlexaff
Ronit Marom, Mahim Jain, Lindsay C. Burrage, I-Wen Song, Brett H. Graham, Chester Brown, Servi J.C. Stevens, Alexander P.A. Stegmann, Andrew T. Gunter, Julie Kaplan, Ralitza H. Gavrilova, Marwan Shinawi, Jill A. Rosenfeld, Yangjin Bae, Alyssa A. Tran, Yuqing Chen, James T. Lu, Richard A. Gibbs, Christine M. Eng, Yaping Yang, Justine Rousseau, Bert B.A. de Vries, Philippe M. Campeau, Brendan Lee

Bibliographic record

VenueHuman Mutation · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicChromatin Remodeling and Cancer
Canadian institutionsCentre Hospitalier Universitaire Sainte-JustineUniversité de Montréal
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Diabetes and Digestive and Kidney DiseasesNational Center for Research ResourcesNational Institute of General Medical SciencesNational Human Genome Research InstituteZonMwACMG Foundation for Genetic and Genomic MedicineNational Cancer InstituteNational Institutes of HealthNational Institute of Allergy and Infectious DiseasesOsteogenesis Imperfecta Foundation
KeywordsIntellectual disabilityBiologyMissense mutationGeneticsRNA splicingGeneMutationChromatin remodelingChromatin

Abstract

fetched live from OpenAlex

Pathogenic variants in genes encoding components of the BRG1-associated factor (BAF) chromatin remodeling complex have been associated with intellectual disability syndromes. We identified heterozygous, novel variants in ACTL6A, a gene encoding a component of the BAF complex, in three subjects with varying degrees of intellectual disability. Two subjects have missense variants affecting highly conserved amino acid residues within the actin-like domain. Missense mutations in the homologous region in yeast actin were previously reported to be dominant lethal and were associated with impaired binding of the human ACTL6A to β-actin and BRG1. A third subject has a splicing variant that creates an in-frame deletion. Our findings suggest that the variants identified in our subjects may have a deleterious effect on the function of the protein by disturbing the integrity of the BAF complex. Thus, ACTL6A gene mutation analysis should be considered in patients with intellectual disability, learning disabilities, or developmental language disorder.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.820
Threshold uncertainty score0.224

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.040
GPT teacher head0.293
Teacher spread0.253 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations32
Published2017
Admission routes1
Has abstractyes

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