ASH1L literature, organized for scientific use.

A Yale-led study directly perturbed ASH1L within a 23-gene CRISPR program across neural progenitors and glutamatergic and GABAergic neurons, with arrayed ASH1L assays and an ash1l zebrafish model. ASH1L loss increased Ki-67-positive neural progenitors and contributed to cell-state-specific convergence analyses.

This is a gene-knockout study, not a graded ASH1L dosage-response experiment or a functional classification of patient alleles. Most network findings are cross-gene convergence results; the reported Seahorse assay did not identify a significant respiratory change for ASH1L.

Targeted perturbation in a mouse memory circuit identified a sequential CAMTA1–TCF4–ASH1L transcriptional cascade. In that task, ASH1L was required later to maintain selected memories over weeks rather than for initial memory formation.

Circuit- and task-specific mouse evidence. It separates memory stabilization from acquisition experimentally but does not define an individual human memory profile or prove progressive decline.

A Yale-led dual-system screen reported ASH1L responses across gene expression and network bursting in human induced neurons and sleep-wake and visual-startle measures in larval zebrafish.

Non-peer-reviewed model-system evidence. It does not establish benefit, safety, dose, timing, or treatment guidance for people with ASH1L-related disorder.

A Yale-led high-throughput resource profiled 520 FDA-approved drugs across nine large-effect autism-gene zebrafish mutants, extending a cross-gene behavioral and pharmacologic platform relevant to future model-based work.

ASH1L was not directly tested in this paper. Rescue validation centered on other gene models, so this is Yale platform context—not ASH1L treatment evidence.

A Yale review of large-effect autism and NDD mechanisms that places ASH1L among high-confidence chromatin and gene-regulation risk genes.

Contextual synthesis rather than an ASH1L-specific phenotype, natural-history, or intervention study.

A Yale-led standardized zebrafish pipeline across ten autism-risk genes, integrating morphology, sleep–wake behavior, sensorimotor response, whole-brain activity, dopaminergic measures, and neuroimmune readouts.

ASH1L was not one of the ten genes tested. This paper is included only as methodological context for the later Yale program and must not be cited as direct ASH1L evidence.

Reports a de novo missense variant with mild autism and an uneven neuropsychological profile, including relative verbal strengths.

Single case; the variant remained a VUS and cannot define pathogenicity or a missense-class severity rule.

Adds a truncating case with comparatively mild reported intellectual disability and reviews previously reported nonsense variants.

Case-report and literature-review evidence; it does not establish a deterministic truncation-position or severity relationship.

Combines clinical phenotyping with two mouse backgrounds, neuronal morphology, seizures, and electrophysiology; reports sex-associated differences in its human and mouse datasets.

Preprint with limited and ascertained human data. It does not establish population-level sex-specific penetrance or prognosis.

Germline and cortical-lineage mouse models show structural birth defects, altered progenitor balance, and cortical-neuron-fate effects.

Developmental mouse findings, including homozygous outcomes, do not predict the course of human heterozygous ASH1L-related disorder.

Refines the catalytic and reader-domain architecture of ASH1L, including H3K4me3 engagement and locus-specific chromatin regulation.

Structure-function evidence does not convert protein position alone into a clinical-severity or treatment prediction.

A focused cohort expanding the published human phenotype and molecular spectrum, with feature-specific denominators.

Retrospective published cohort; its denominators cannot be substituted for the connected 61-person dataset or a population estimate.

Uses ASH1L-variant human iPSC-derived neurons to examine chromatin, transcription, splicing, morphology, and in-vitro pharmacologic rescue of neurite phenotypes.

Preprint and in-vitro evidence. Tazemetostat or vorinostat rescue in cultured neurons is not clinical treatment evidence.

Links prefrontal-cortex hyperexcitability to social and seizure-related phenotypes in a mouse model and tests circuit-level chemogenetic suppression.

Circuit intervention in mice is not evidence for a human therapy or for a single cortical mechanism across ASH1L variants.

Defines an ASH1L-dependent osteoclast differentiation and bone-resorption mechanism in the tested systems.

Biological rationale for bone-focused measurement, not evidence that an individual skeletal finding is ASH1L-mediated.

Connects neuronal Ash1l, activity-dependent let-7b release, and cutaneous inflammatory signaling in a psoriasis model.

Disease-specific animal work; it does not establish psoriasis or a shared neurocutaneous mechanism in ASH1L-related NDD.

Biochemical work showed that Caf1 binds the Ash1 complex near its reader-domain region, senses unmodified H3K4, and regulates H3K36 methyltransferase activity.

Mechanistic protein-complex and chromatin evidence. It does not test human ASH1L variants, neurodevelopmental phenotypes, gene dosage, or treatment response.

Tests how full-length MRG15 enhances ASH1L nucleosome engagement and catalytic activity.

Protein-complex mechanism does not establish patient-specific MRG15 dysfunction or clinical phenotype.

In Drosophila, Ash1-dependent H3K36me2 and its Caf1-55 and MRG15 complex partners were required for normal cardiac development and function.

Distal species evidence involving the fly Ash1 ortholog. It supports a developmental tissue mechanism but does not establish a human cardiac phenotype or screening indication.

Connects Ash1l haploinsufficiency to developmental and behavioral phenotypes and implicates EphA7-dependent synaptic refinement in mice.

Model-supported pathway, not a validated human biomarker or treatment target.

He Lab work reports locomotor and metabolic hyperactivity, disturbed sleep, lower induced-seizure threshold, and increased regional neuronal activity in Ash1l-deficient mice.

Mouse behavioral and physiological phenotypes do not establish a corresponding human state mechanism or clinical endpoint.

Ash1l overexpression in mouse fetal ovaries altered DNA double-strand-break repair signaling and increased oocyte apoptosis in the tested system.

This is an overexpression experiment—the opposite perturbation direction from haploinsufficiency—and does not establish fertility risk in people with ASH1L-related disorder.

Provides structural information about the PHD finger and histone-tail recognition.

Cancer context; it does not support a clinical inference for ASH1L-related neurodevelopmental disorder.

Examines common-variant association with Tourette syndrome using family-based and case-control analyses.

The family transmission result and nonsignificant case-control result concern common-variant risk and must not be conflated with rare pathogenic ASH1L loss-of-function disorder.

Technical report on genome editing and neuronal differentiation challenges in ASH1L-haploinsufficient stem-cell systems.

Preprint focused on model generation and laboratory workflow, not human phenotype or treatment.

He Lab developmental neural-lineage deletion supports effects on cortical development, myelination, cognition, and behavior.

Nestin-lineage mouse deletion includes multiple neural cell classes and does not isolate a mature astrocyte, microglial, or human mechanism.

Region-specific mouse work links Ash1l deficiency to altered transcription, neuronal hyperactivity, excitation/inhibition imbalance, and seizures.

Regional perturbation does not define all cell types, clinical variants, or human seizure trajectories.

He Lab mouse study reports postnatal vorinostat-associated improvement in selected social and memory measures.

Preclinical mouse pharmacology. It does not establish human efficacy, safety, timing, or clinical use of vorinostat.

Develops chemical probes that inhibit ASH1L catalytic activity in leukemia models.

ASH1L-related NDD is primarily a reduced-dosage disorder; an ASH1L inhibitor is not a therapeutic rationale for haploinsufficiency.

Reviews ASH1L genetics and model biology across Tourette syndrome, autism, and intellectual disability.

Narrative synthesis; disease contexts and variant mechanisms should not be merged into one clinical phenotype.

Twin report relevant to epilepsy, inheritance, and within-family phenotypic comparison.

Related individuals are not independent recurrence events and cannot establish penetrance.

Human genetic analysis with functional and animal-model follow-up supporting ASH1L as a Tourette-susceptibility gene.

Tourette-susceptibility findings are a distinct ascertainment and disease context from ASH1L haploinsufficiency-related NDD.

Foundational focused human series supporting de novo loss-of-function as a disease mechanism.

Small early series; it does not define the full phenotype, natural history, or prevalence of individual features.

Structural work defined how MRG15 binding releases ASH1L catalytic autoinhibition and activates its H3K36 methyltransferase function.

Purified-complex structure and biochemistry do not establish the functional consequence of an individual human variant or a clinical severity relationship.

Defines MRG15-associated activation and the autoinhibitory architecture of the ASH1L catalytic region.

Structural complex evidence is not a clinical phenotype or variant-severity assay.

In mouse muscle and myoblast systems, Ash1l opposed Polycomb repression at selected myogenic genes, activated Cdon, and supported myoblast fusion during formation and regeneration.

Direct muscle-lineage evidence, but not proof of a primary human myopathy or an explanation for every tone, gait, fatigue, or recovery finding.

Historically Yale-affiliated study showing an extra-neural role in epidermal differentiation, proliferation, and wound repair in mice.

Mouse epidermal biology does not establish a universal human skin phenotype in ASH1L-related NDD.

Supports an Ash1l-dependent chromatin mechanism in induced regulatory T-cell polarization and autoimmunity models.

Immune model evidence does not establish an immune phenotype in heterozygous ASH1L-related disorder.

Biochemical and structural work supporting MRG15-dependent activation of ASH1L methyltransferase activity.

Cofactor activation in purified and cellular systems does not establish patient-specific dysfunction.

Early syndrome-level case report that helped establish the clinical association between disruptive ASH1L variation and neurodevelopmental disorder.

Single early case; not a complete syndrome definition or feature-frequency estimate.

Shows activity-dependent recruitment of Ash1l and H3K36me2 at the Nrxn1α promoter in mouse cortical neurons.

One-locus in-vitro/model result; it does not establish fluctuating human cognition, regression, or treatment response.

Establishes an ASH1L role in hematopoietic stem-cell quiescence and self-renewal.

Mechanistic tissue context, not evidence of a blood or immune manifestation in an individual with ASH1L-related NDD.

ASH1L catalytic activity opposed Polycomb repression and supported timely activation of selected developmental genes in mouse differentiation systems.

Selected-locus model evidence; it does not establish genome-wide H3K27me3 spread or failed bivalent-domain resolution in human ASH1L patient cells.

Defines an Ash1l–A20/Tnfaip3 mechanism restraining inflammatory signaling in macrophage and mouse models.

Tissue- and model-specific; it does not establish a human cytokine or immune phenotype in ASH1L haploinsufficiency.

Historically Yale-affiliated molecular work examining ASH1L-dependent Hox regulation and chromatin function.

Foundational gene-regulation evidence from a non-neurodevelopmental context; not human phenotype evidence.

Foundational catalytic-domain structure demonstrating an autoinhibitory loop that blocks substrate access in the inactive state.

Purified catalytic-domain structure does not define cell-type phenotype or clinical variant effect.

Biochemical evidence that H3K36 methylation can directly inhibit PRC2-mediated H3K27 methylation.

Mark-level antagonism does not show that ASH1L haploinsufficiency produces global Polycomb spreading or a uniform human clinical state.

Foundational evidence for H3K4me3/H3K27me3 bivalent domains that poise developmental regulators in embryonic stem cells.

Bivalency is a general developmental-chromatin concept. Its abnormal resolution has not yet been demonstrated broadly in ASH1L patient cells.