setd1a

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setd1a

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">setd1a</th>
</tr>
<tr>
<td class="label">Full Name</td>
<td>SET Domain Containing 1A, Histone Lysine Methyltransferase</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>SETD1A</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>KMT2F, SET1, SET1A</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>16p11.2</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein-coding</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[611052](https://omim.org/entry/611052)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>[O15047](https://www.uniprot.org/uniprot/O15047)</td>
</tr>
<tr>
<td class="label">HGNC</td>
<td>[29010](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:29010)</td>
</tr>
<tr>
<td class="label">Entrez Gene</td>
<td>[9739](https://www.ncbi.nlm.nih.gov/gene/9739)</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>[ENSG00000099381](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000099381)</td>
</tr>
<tr>
<td class="label">Variant</td>
<td>Type</td>
</tr>
<tr>
<td class="label">p.R913*</td>
<td>Nonsense</td>
</tr>
<tr>
<td class="label">p.G535Afs*12</td>
<td>Frameshift</td>
</tr>
<tr>
<td class="label">c.4582-2A>G</td>
<td>Splice-site</td>
</tr>
<tr>
<td class="label">16p11.2 microdeletion</td>
<td>CNV</td>
</tr>
<tr>
<td cla

...

setd1a

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">setd1a</th>
</tr>
<tr>
<td class="label">Full Name</td>
<td>SET Domain Containing 1A, Histone Lysine Methyltransferase</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>SETD1A</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>KMT2F, SET1, SET1A</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>16p11.2</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein-coding</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[611052](https://omim.org/entry/611052)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>[O15047](https://www.uniprot.org/uniprot/O15047)</td>
</tr>
<tr>
<td class="label">HGNC</td>
<td>[29010](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:29010)</td>
</tr>
<tr>
<td class="label">Entrez Gene</td>
<td>[9739](https://www.ncbi.nlm.nih.gov/gene/9739)</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>[ENSG00000099381](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000099381)</td>
</tr>
<tr>
<td class="label">Variant</td>
<td>Type</td>
</tr>
<tr>
<td class="label">p.R913*</td>
<td>Nonsense</td>
</tr>
<tr>
<td class="label">p.G535Afs*12</td>
<td>Frameshift</td>
</tr>
<tr>
<td class="label">c.4582-2A>G</td>
<td>Splice-site</td>
</tr>
<tr>
<td class="label">16p11.2 microdeletion</td>
<td>CNV</td>
</tr>
<tr>
<td class="label">rs3782089</td>
<td>Promoter SNP</td>
</tr>
<tr>
<td class="label">rs11150601</td>
<td>Intron SNP</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

SETD1A

</div>

Pathway / Interaction Diagram

Mermaid diagram (expand to render)

Overview

SETD1A is a human gene. Variants in SETD1A have been implicated in Schizophrenia, Alzheimer's Disease, Neurodevelopmental Disorder (SETD1A-Related). This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

SETD1A (SET Domain Containing 1A), also known as KMT2F, encodes a histone H3 lysine 4 (H3K4) methyltransferase that is the catalytic subunit of the SETD1A/COMPASS complex. SETD1A deposits H3K4me3 at promoters of actively transcribed genes, a histone mark essential for transcription initiation and RNA polymerase II recruitment.[1] SETD1A is one of six mammalian H3K4 methyltransferases in the KMT2/MLL family and has emerged as one of the strongest individual gene risk factors for schizophrenia. In [neurons](/entities/neurons), SETD1A regulates synaptic gene expression, axonal branching, and cortical neuron morphology. Haploinsufficiency causes a neurodevelopmental syndrome with cognitive impairment and increased risk for neuropsychiatric and neurodegenerative disorders including [Alzheimer's disease](/diseases/alzheimers-disease).[@m2023]

Function and Mechanism

SETD1A contains an N-terminal RNA recognition motif (RRM), a central region mediating COMPASS interactions, and a C-terminal SET domain catalyzing H3K4 methylation. The SET domain requires assembly into the COMPASS complex (with WDR5, RBBP5, ASH2L, DPY30) for catalytic activity.

H3K4me3 Deposition at Promoters

The SETD1A/COMPASS complex deposits H3K4me3 at transcription start sites of actively transcribed genes. H3K4me3 is read by the TAF3 subunit of TFIID, bridging [histone modifications](/entities/histone-modifications) to RNA polymerase II pre-initiation complex assembly. SETD1A is responsible for the bulk of H3K4me3 at most gene promoters in mammalian cells, distinguishing it from MLL1/2 (which target developmental/Hox gene promoters) and MLL3/4 (which target enhancers with H3K4me1).[1]

Transcriptional Regulation in Neurons

In cortical neurons, SETD1A-dependent H3K4me3 is critical for expression of synaptic genes including glutamate receptor subunits (GRIN1, GRIN2A, GRIN2B), scaffolding proteins (DLG4/PSD-95, SHANK3), and activity-dependent transcription factors (MEF2C, CREB1).[@j2019] SETD1A haploinsufficiency reduces H3K4me3 at these promoters by 30-50%, producing measurable decreases in synaptic protein levels and synaptic transmission efficacy.[2]

Axonal Development and Neuronal Morphology

SETD1A regulates axonal branching through transcriptional control of cytoskeletal regulators. Setd1a heterozygous knockout mice exhibit reduced axonal branch complexity in cortical pyramidal neurons, decreased dendritic spine density, and deficits in cortical circuit connectivity. These morphological defects are partially rescuable by increasing H3K4me3 through pharmacological inhibition of KDM5 demethylases ([KDM5B](/genes/kdm5b), [KDM5C](/genes/kdm5c)).[3]

DNA Damage Response

SETD1A is recruited to DNA double-strand breaks where it deposits H3K4me3 to facilitate homologous recombination repair. In post-mitotic neurons that primarily use NHEJ, SETD1A's repair function intersects with [KDM4C](/genes/kdm4c)-mediated H3K9me3 removal at damage sites. SETD1A loss increases DNA damage burden, accelerating aging-related neuronal vulnerability.[4]

Mitochondrial Function and Oxidative Stress

Recent research has revealed a critical role for SETD1A in mitochondrial dynamics and neuronal survival under oxidative stress conditions. SETD1A regulates expression of key mitochondrial fusion and fission genes including MFN1, MFN2, OPA1, and DRP1 (DNM1L). Loss of SETD1A leads to fragmented mitochondria, reduced ATP production, and increased susceptibility to oxidative damage.[14]

In neurons, SETD1A deficiency causes impaired mitophagy—the selective autophagy process that removes damaged mitochondria. SETD1A-dependent H3K4me3 at promoters of PINK1 and PARKIN (PRKN) genes is required for their expression. Given that [PINK1](/genes/pink1) and [PARKIN](/genes/parkin) are central to mitophagy in [Parkinson's disease](/diseases/parkinsons-disease), SETD1A decline may contribute to the accumulation of dysfunctional mitochondria in dopaminergic neurons.[14]

Disease Associations

Schizophrenia

Loss-of-function variants in SETD1A are among the strongest individual gene risk factors for schizophrenia, with an odds ratio exceeding 35.[@j2021] Exome sequencing studies have identified protein-truncating variants in SETD1A in ~0.1% of schizophrenia cases. Affected individuals typically present with early-onset schizophrenia, cognitive impairment, and developmental delays preceding psychosis onset.[2]

Recent genome-wide association studies have identified multiple SETD1A variants associated with schizophrenia susceptibility. The rs11150601 intron variant shows significant association specifically in female patients from the UK Biobank cohort, suggesting sex-specific effects of SETD1A genetic variation on schizophrenia risk.[13]

Alzheimer's Disease

In [Alzheimer's disease](/diseases/alzheimers-disease), SETD1A expression declines in vulnerable brain regions, leading to loss of H3K4me3 at synaptic gene promoters. This contributes to the synaptic gene downregulation that precedes neuronal death. Additionally, reduced SETD1A activity impairs DNA repair capacity, increasing vulnerability to oxidative DNA damage driven by [amyloid-beta](/proteins/amyloid-beta) and neuroinflammation.[5]

The interaction between SETD1A and [tau](/proteins/tau) pathology involves competition for chromatin access: hyperphosphorylated [tau](/proteins/tau) associates with H3K4me3-marked promoters and disrupts SETD1A-COMPASS chromatin occupancy, amplifying H3K4me3 loss at synaptic genes.[5]

SETD1A interacts with multiple pathological features of Alzheimer's disease beyond chromatin relaxation. In cellular models, amyloid-beta oligomers suppress SETD1A expression and COMPASS complex formation, creating a feedforward loop where amyloid pathology impairs the epigenetic machinery needed for synaptic gene expression.[5]

SETD1A also modulates neuroinflammation through regulation of glial cell gene programs. In microglia, SETD1A controls expression of TNF, IL1B, and IL6 in response to amyloid-beta exposure. SETD1A deficiency leads to exaggerated neuroinflammatory responses, amplifying neuronal vulnerability.[14]

Heterozygous loss-of-function variants cause a recognizable neurodevelopmental syndrome (OMIM #619811) characterized by intellectual disability (typically mild-moderate), speech and language delay, behavioral features (ADHD, autism spectrum traits), and variable facial dysmorphism. Most identified variants are protein-truncating (frameshift, nonsense, splice-site) and arise de novo.[6]

Parkinson's Disease

SETD1A-dependent H3K4me3 at dopaminergic neuron-specific gene promoters (including TH, NURR1, PITX3) is required for maintenance of dopaminergic identity. Age-related SETD1A decline in the substantia nigra may contribute to dopaminergic neuron vulnerability in [Parkinson's disease](/diseases/parkinsons-disease), though direct genetic associations remain under investigation.[7]

Recent population-based studies have identified epigenetic mechanisms linking environmental factors to PD risk through SETD1A. Analysis of the UK Biobank cohort revealed that educational attainment—a known protective factor against PD—correlates with SETD1A expression levels, suggesting that higher SETD1A activity may buffer against dopaminergic neurodegeneration through enhanced chromatin regulation of neuroprotective genes.[11]

Molecular Mechanisms

SETD1A is ubiquitously expressed across all brain regions, with highest levels in the cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and thalamus. During development, SETD1A expression peaks during active neurogenesis and synaptogenesis (embryonic day 14 through postnatal day 14 in mice), then declines to moderate adult levels.[2]

At the cellular level, SETD1A is expressed in all major neural cell types but is most abundant in excitatory projection neurons. Chandelier and parvalbumin-positive (PV+) interneurons also express SETD1A, consistent with their dysfunction in SETD1A-haploinsufficient schizophrenia models. Oligodendrocyte expression of SETD1A regulates myelination gene programs.[3]

Epigenetic Regulation in Aging Brain

Age-related decline in SETD1A expression represents a conserved feature of brain aging across species. Transcriptomic analyses of human brain tissue show progressive reduction in SETD1A mRNA levels starting in the fifth decade of life, with the most pronounced declines in the [hippocampus](/brain-regions/hippocampus) and [prefrontal cortex](/brain-regions/prefrontal-cortex). This decline correlates with reduced H3K4me3 at synaptic gene promoters and provides a mechanistic link between normal aging and increased susceptibility to neurodegenerative diseases.[14]

Mouse models with conditional Setd1a knockout in adult neurons show accelerated cognitive decline, validating SETD1A as a key regulator of age-related cognitive function. These mice exhibit synaptic protein downregulation, dendritic spine loss, and impaired long-term potentiation (LTP) even in the absence of amyloid or tau pathology, suggesting that SETD1A decline alone can drive cognitive vulnerability.[15]

Common Variants

Structural Biology of SETD1A

The SETD1A protein consists of multiple functional domains that coordinate its enzymatic activity and cellular localization. Understanding these domains provides insight into disease-causing mutations and therapeutic targeting opportunities.

Domain Architecture

SETD1A contains several distinct domains: an N-terminal RNA recognition motif (RRM) that mediates interactions with nascent transcripts and facilitates promoter targeting; a central region containing multiple PHD fingers that recognize unmodified histone H3 tails and contribute to target gene specificity; and the C-terminal SET domain that catalyzes H3K4 methylation. The SET domain requires assembly into the larger COMPASS (Complex of Proteins Associated with Set1) complex for full catalytic activity.[1]

The COMPASS core consists of WDR5 (WD repeat-containing protein 5), RBBP5 (Retinoblastoma-binding protein 5), ASH2L (Absent, Small, Or Homeotic 2-like), and DPY30. WDR5 binds directly to SETD1A through a conserved "WDR5 interaction" (WDI) motif, bridging SETD1A to the rest of the complex. Crystal structures have revealed that the SET domain adopts an auto-inhibited conformation in the absence of COMPASS assembly, with the active site blocked by an N-SET loop. COMPASS binding relieves this inhibition, positioning the substrate H3 tail for methylation.[10]

Disease-Causing Variants

Over 200 pathogenic variants in SETD1A have been identified in individuals with neurodevelopmental disorders. These variants are enriched in the SET domain (affecting catalytic function) and the WDI motif (impairing COMPASS assembly). Functional studies show that most pathogenic variants reduce H3K4me3 activity by >80%, consistent with haploinsufficiency as the disease mechanism.[2]

Common pathogenic variants include: p.R913 (nonsense, truncates SET domain), p.G535Afs12 (frameshift, destabilizes protein), and splice-site variants that cause exon skipping. Missense variants in the SET domain (e.g., p.R1280W, p.L1300F) typically show partial loss of function (30-70% reduction) and may present with milder phenotypes.[6]

COMPASS Complex and Epigenetic Regulation

The SETD1A/COMPASS complex represents the major H3K4me3-writing machinery in mammalian cells, and its regulation is tightly coupled to cellular metabolism, signaling, and stress responses.

Transcriptional Co-activation

SETD1A/COMPASS functions as a co-activator for RNA polymerase II transcription by depositing H3K4me3 at promoter nucleosomes. This mark is read by multiple effector proteins, including TAF3 (TBP-associated factor 3) in the TFIID complex, which directly binds H3K4me3 through its PHD finger. This interaction stabilizes TFIID at promoters and promotes PIC (pre-initiation complex) assembly.[1]

Beyond TFIID, SETD1A-generated H3K4me3 recruits additional co-activators, including the histone acetyltransferases p300/CBP, which acetylate histone H3 and H4 to further open chromatin. This feedforward mechanism ensures robust transcriptional activation of SETD1A target genes, particularly those involved in synaptic function and neuronal survival.[1]

Regulation by Cellular Signaling

SETD1A/COMPASS activity is modulated by multiple signaling pathways. Phosphorylation of SETD1A by [CK2](/proteins/casein-kinase-2) enhances COMPASS stability and H3K4me3 activity. In contrast, stress-activated kinases such as JNK and p38 can phosphorylate SETD1A to reduce its chromatin binding, providing a mechanism for stress-induced transcriptional repression.[14]

The availability of S-adenosylmethionine (SAM)—the methyl donor for H3K4 methylation—links COMPASS activity to cellular metabolism. Under conditions of reduced SAM (e.g., mitochondrial dysfunction, oxidative stress), SETD1A activity decreases, contributing to the epigenetic changes observed in neurodegeneration.[15]

Therapeutic Implications

SETD1A haploinsufficiency provides a clear therapeutic rationale: restoring H3K4me3 levels at target promoters could ameliorate cognitive deficits in SETD1A-related disorders and potentially in AD. Two main approaches are being investigated:

KDM5 inhibitor therapy: Pharmacological inhibition of [KDM5B](/genes/kdm5b)/[KDM5C](/genes/kdm5c) H3K4 demethylases increases H3K4me3 levels genome-wide, partially compensating for SETD1A loss. KDM5 inhibitors (including CPI-455 and KDM5-C70) have shown cognitive improvement in Setd1a-haploinsufficient mouse models.[9]

SETD1A activator development: Small molecules that enhance SETD1A-COMPASS catalytic activity or stabilize the complex represent an alternative strategy. The requirement for COMPASS assembly creates opportunities for allosteric activators targeting the WDR5-SETD1A interface.[10]

Gene therapy: AAV-mediated SETD1A supplementation in neurons is being explored but faces challenges due to the large gene size (>5 kb coding sequence exceeding AAV packaging limits). Mini-gene constructs retaining the SET domain and critical COMPASS interaction regions are under development.[3]

Mitochondrial protection: Given the role of SETD1A in mitochondrial gene regulation, small molecules that enhance mitochondrial function (e.g., PINK1 activators, mitophagy inducers) may provide indirect therapeutic benefit in SETD1A-deficient states.[14]

Comparative Biology and Evolution

The SETD1A gene and its COMPASS complex are evolutionarily conserved across eukaryotes, reflecting the fundamental importance of H3K4me3 in transcriptional regulation. Yeast Set1, the ancestral ortholog of SETD1A, functions as the sole H3K4 methyltransferase in Saccharomyces cerevisiae, establishing the core COMPASS architecture over 1 billion years ago. The expansion to six mammalian H3K4 methyltransferases (SETD1A, SETD1B, MLL1, MLL2, MLL3, MLL4) reflects functional specialization during vertebrate evolution.

In Drosophila melanogaster, the Set1 ortholog (dSet1) is required for [homeotic gene](/entities/homeotic-genes) expression and proper body plan development. Knockdown of dSet1 leads to lethal developmental defects, demonstrating the non-redundant essential function of this enzyme family. Notably, fly SETD1A orthologs show particular importance in neuronal development, with mutants displaying defects in learning and memory circuits.

Vertebrate SETD1A and SETD1B arose from a gene duplication event in the common ancestor of teleost fish and tetrapods. Functional divergence included acquisition of novel target gene specificity, with SETD1A becoming the predominant methyltransferase for synaptic genes while SETD1B assumed greater importance in mitochondrial gene regulation. This specialization is reflected in the distinct phenotypic consequences of SETD1A versus SETD1B loss in mice: Setd1a haploinsufficiency produces neurodevelopmental and cognitive deficits, while Setd1b deficiency causes embryonic lethality with cardiac and neural tube defects.

The rapid evolution of SETD1A regulatory regions in primates—including species-specific enhancer elements in the brain—suggests that SETD1A expression may have been a target of positive selection during human evolution. This hypothesis is supported by the presence of human-specific SETD1A expression patterns in the prefrontal cortex, a brain region expanded in primates.[13]

Animal Models

Mouse models have been instrumental in understanding SETD1A function in the nervous system and validating therapeutic approaches.

Knockout and Knockdown Models

heterozygous Setd1a knockout mice (Setd1a+/-) recapitulate key features of SETD1A haploinsufficiency in humans. These mice show reduced H3K4me3 at synaptic gene promoters, decreased synaptic protein levels, impaired spatial learning and memory, and behavioral abnormalities relevant to schizophrenia (reduced prepulse inhibition, increased locomotor activity in novel environments).[3]

Conditional knockout models targeting Setd1a in adult neurons allow separation of developmental from adult-onset functions. These mice develop normally but exhibit rapid cognitive decline after Setd1a deletion, demonstrating that SETD1A is required for maintenance of cognitive function in the adult brain, not just during development.[15]

Neuron-specific Setd1a knockdown using AAV-mediated RNAi produces similar phenotypes, providing a model for acute SETD1A loss that mirrors the age-related decline observed in human brains. These models are being used to test therapeutic interventions.[9]

Rescue Experiments

Multiple studies have demonstrated rescue of Setd1a haploinsufficiency phenotypes through various approaches. Pharmacological KDM5 inhibition using CPI-455 or KDM5-C70 restores H3K4me3 levels, improves synaptic protein expression, and rescues cognitive deficits in Setd1a+/- mice. Importantly, rescue is observed even when treatment begins after symptom onset, suggesting therapeutic relevance for patients with SETD1A-related disorders.[9]

Viral delivery of wild-type Setd1a using AAV vectors partially rescues phenotypes when administered during early development. However, adult administration shows limited efficacy, likely due to the large coding sequence and challenges achieving sufficient neuronal transduction.[3]

External Links

[OMIM: 611052](https://omim.org/entry/611052)
[GeneCards: SETD1A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SETD1A)
[UniProt: O15047](https://www.uniprot.org/uniprot/O15047)
[Allen Brain Atlas: SETD1A](https://portal.brain-map.org/search?query=SETD1A)
[GTEx Portal: SETD1A](https://gtexportal.org/home/gene/SETD1A)

References

[Shilatifard, The COMPASS family of histone H3K4 methylases: mechanisms of regulation in development and disease pathogenesis (2012)](https://doi.org/10.1146/annurev-biochem-051710-134100)

[Singh et al., Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders (2016)](https://doi.org/10.1038/nn.4267)

[Mukai et al., Recapitulation and reversal of schizophrenia-related phenotypes in Setd1a-deficient mice (2019)](https://doi.org/10.1016/j.neuron.2019.09.014)

[Hoshii et al., A Non-catalytic function of SETD1A regulates cyclin K and the DNA damage response (2018)](https://doi.org/10.1016/j.cell.2018.07.032)

[Frost et al., Tau promotes neurodegeneration through global chromatin relaxation (2014)](https://doi.org/10.1038/nn.3639)

[Kummeling et al., Expanding the phenotypic spectrum of SETD1A-related disorder (2021)](https://doi.org/10.1002/ajmg.a.62037)

[Basavarajappa & Bhatt, Epigenetic mechanisms in neurological and neurodegenerative diseases (2021)](https://doi.org/10.3389/fgene.2021.747927)

[Nagahama et al., Setd1a insufficiency in mice attenuates excitatory synaptic function and recapitulates schizophrenia-related behavioral abnormalities (2020)](https://doi.org/10.1016/j.celrep.2020.108126)

[Johansson et al., Structural analysis of human KDM5B guides histone demethylase inhibitor development (2016)](https://doi.org/10.1038/nsmb.3270)

[Li et al., Structural basis for activity regulation of MLL family methyltransferases (2016)](https://doi.org/10.1038/nature16952)

[Yin et al., Epigenetic Mediating Mechanisms in Parkinson's Disease: The Impact of Educational Attainment on SETD1A Expression (2025)](https://doi.org/10.1002/mds.70010)

[Wainberg et al., Shared genetic risk loci between Alzheimer's disease and related dementias, Parkinson's disease, and amyotrophic lateral sclerosis (2023)](https://doi.org/10.1186/s13195-023-01244-3)

[Lehrer & Rheinstein, The rs11150601 Intron Variant of SETD1A Is Associated With Female Schizophrenia in the UK Biobank Cohort (2026)](https://doi.org/10.1002/ajmg.b.33054)

[Takahashi et al., SETD1A regulates mitochondrial dynamics and protects against oxidative stress-induced neuronal death (2024)](https://doi.org/10.1016/j.nbd.2024.106175)

[Chen et al., Loss of SETD1A accelerates age-related cognitive decline through mitochondrial dysfunction (2023)](https://doi.org/10.1016/j.aging.2023.105892)

Pathway Diagram

The following diagram shows the key molecular relationships involving setd1a discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

SETD1A

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-setd1a
kg_node_id	SETD1A
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-ff00f1e8a99c
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-setd1a'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

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Certainty

25%

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Outgoing

24

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

setd1a

setd1a

setd1a

Pathway / Interaction Diagram

Overview

Function and Mechanism

H3K4me3 Deposition at Promoters

Transcriptional Regulation in Neurons

Axonal Development and Neuronal Morphology

DNA Damage Response

Mitochondrial Function and Oxidative Stress

Disease Associations

Schizophrenia

Alzheimer's Disease

Parkinson's Disease

Molecular Mechanisms

Epigenetic Regulation in Aging Brain

Common Variants

Structural Biology of SETD1A

Domain Architecture

Disease-Causing Variants

COMPASS Complex and Epigenetic Regulation

Transcriptional Co-activation

Regulation by Cellular Signaling

Therapeutic Implications

See Also

Comparative Biology and Evolution

Animal Models

Knockout and Knockdown Models

Rescue Experiments

External Links

References

Pathway Diagram

💬 Discussion