MétaCan
Menu
Back to cohort
Record W2965961249 · doi:10.1038/s41467-019-11437-w

Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome

2019· article· en· W2965961249 on OpenAlexafffund
Abigail U. Carbonell, Chang Hoon Cho, Jaafar Tindi, Pamela A. Counts, Juliana C. Bates, Hediye Erdjument‐Bromage, Svetlana Cvejic, Alana Iaboni, Ifat Kvint, J. Rosensaft, Ehud Banne, Evdokia Anagnostou, Thomas A. Neubert, Stephen W. Scherer, Sophie Molholm, Bryen A. Jordan

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsHospital for Sick ChildrenUniversity of TorontoSickKids FoundationHolland Bloorview Kids Rehabilitation Hospital
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute on AgingIntellectual and Developmental Disabilities Research CenterOntario Brain InstituteNational Institute of Mental HealthHospital for Sick ChildrenNational Center for Advancing Translational SciencesWellcome TrustNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesAutism SpeaksNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsHaploinsufficiencyNeurodevelopmental disorderAutism spectrum disorderAutismPhenotypeInteractomeNeuroscienceRett syndromeGeneticsBiologyBioinformaticsGeneMedicinePsychiatry

Abstract

fetched live from OpenAlex

Neurodevelopmental disorders, including autism spectrum disorder, have complex polygenic etiologies. Single-gene mutations in patients can help define genetic factors and molecular mechanisms underlying neurodevelopmental disorders. Here we describe individuals with monogenic heterozygous microdeletions in ANKS1B, a predicted risk gene for autism and neuropsychiatric diseases. Affected individuals present with a spectrum of neurodevelopmental phenotypes, including autism, attention-deficit hyperactivity disorder, and speech and motor deficits. Neurons generated from patient-derived induced pluripotent stem cells demonstrate loss of the ANKS1B-encoded protein AIDA-1, a brain-specific protein highly enriched at neuronal synapses. A transgenic mouse model of Anks1b haploinsufficiency recapitulates a range of patient phenotypes, including social deficits, hyperactivity, and sensorimotor dysfunction. Identification of the AIDA-1 interactome using quantitative proteomics reveals protein networks involved in synaptic function and the etiology of neurodevelopmental disorders. Our findings formalize a link between the synaptic protein AIDA-1 and a rare, previously undefined genetic disease we term ANKS1B haploinsufficiency syndrome.

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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.934
Threshold uncertainty score0.449

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 science0.0010.001
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 head0.013
GPT teacher head0.265
Teacher spread0.252 · 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 designBench or experimental
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

Citations38
Published2019
Admission routes2
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicGenetics and Neurodevelopmental DisordersFrench-language works237,207