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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DLGAP2
DLG associated protein 2
Chromosome 8 · 8p23.3
NCBI Gene: 9228Ensembl: ENSG00000198010.13HGNC: HGNC:2906UniProt: A0A1B0GTN4
38PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmolecular adaptor activityglutamatergic synapsemodulation of chemical synaptic transmissionCOVID-19tooth diseaseself-injurious ideationcervical carcinoma
✦AI Summary

DLGAP2 encodes SAP90/PSD-95-associated protein 2 (SAPAP2), a postsynaptic scaffolding protein that regulates synaptic function and cognitive processes 1. The protein localizes to the postsynaptic density of glutamatergic synapses where it modulates synaptic plasticity and neurotransmission 2. DLGAP2 undergoes alternative splicing with tissue-specific expression patterns in brain and testis 1. The gene plays a complex role in cognitive function, as overexpression impairs synaptic plasticity and exacerbates Alzheimer's disease-related memory deficits in mouse models 3. Conversely, lower cortical DLGAP2 expression is associated with increased amyloid plaques, neurofibrillary tangles, and accelerated cognitive decline in Alzheimer's disease patients 4. DLGAP2 is subject to extensive epigenetic regulation through DNA methylation, which influences its expression and function 5. Clinically, DLGAP2 variants and methylation changes are associated with multiple neuropsychiatric conditions including schizophrenia, alcohol dependence, autism spectrum disorders, and developmental delays 267. The gene appears to serve as a critical interface between genetic susceptibility and environmental factors in neurodevelopmental and psychiatric disorders, with methylation status potentially serving as a biomarker for treatment response in alcohol dependence 6.

Sources cited
1
DLGAP2 encodes SAP90/PSD-95-associated protein 2 and undergoes alternative splicing
PMID: 10854099
2
SAPAP2 localizes to postsynaptic density and is associated with schizophrenia susceptibility
PMID: 24416398
3
DLGAP2 overexpression impairs synaptic plasticity and worsens AD-related memory deficits
PMID: 41025221
4
Lower DLGAP2 expression associates with AD pathology and cognitive decline
PMID: 32877673
5
DLGAP2 is regulated by genotype-dependent DNA methylation
PMID: 31745236
6
DLGAP2 methylation changes predict alcohol dependence treatment response
PMID: 38364647
7
DLGAP2 is a candidate gene for neurodevelopmental disorders and autism spectrum disorders
PMID: 33925474
Disease Associationsⓘ20
COVID-19Open Targets
0.33Weak
tooth diseaseOpen Targets
0.30Weak
self-injurious ideationOpen Targets
0.30Weak
cervical carcinomaOpen Targets
0.29Weak
schizophreniaOpen Targets
0.29Weak
brain cancerOpen Targets
0.28Weak
complex regional pain syndromeOpen Targets
0.28Weak
lymphatic system diseaseOpen Targets
0.28Weak
rectosigmoid junction neoplasmOpen Targets
0.28Weak
response to antihypertensive drugOpen Targets
0.28Weak
ovarian neoplasmOpen Targets
0.27Weak
connective tissue diseaseOpen Targets
0.27Weak
placenta praeviaOpen Targets
0.26Weak
Abruptio PlacentaeOpen Targets
0.26Weak
acute tonsillitisOpen Targets
0.25Weak
brain aneurysmOpen Targets
0.25Weak
placental retentionOpen Targets
0.25Weak
pyogenic granulomaOpen Targets
0.25Weak
Alzheimer diseaseOpen Targets
0.25Weak
male reproductive organ cancerOpen Targets
0.25Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NLGN2Protein interaction100%NLGN1Protein interaction100%NLGN3Protein interaction100%NLGN4XProtein interaction100%DLG4Protein interaction99%HOMER1Protein interaction98%
Tissue Expression6 tissues
Brain
100%
Liver
15%
Ovary
7%
Heart
2%
Bone Marrow
2%
Lung
2%
Gene Interaction Network
Click a node to explore
DLGAP2NLGN2NLGN1NLGN3NLGN4XDLG4HOMER1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt A0A1B0GTN4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.42Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.30 [0.22–0.42]
RankingsWhere DLGAP2 stands among ~20K protein-coding genes
  • #10,459of 20,598
    Most Researched38
  • #2,267of 17,882
    Most Constrained (LOEUF)0.42 · top quartile
Genes detectedDLGAP2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
8p23.2-pter Microdeletions: Seven New Cases Narrowing the Candidate Region and Review of the Literature.
PMID: 33925474
Genes (Basel) · 2021
1.00
2
Positional cloning and characterisation of the human DLGAP2 gene and its exclusion in progressive epilepsy with mental retardation.
PMID: 10854099
Eur J Hum Genet · 2000
0.90
3
Evaluation of hippocampal DLGAP2 overexpression on cognition, synaptic function, and dendritic spine structure in a translationally relevant AD mouse model.
PMID: 41025221
Alzheimers Dement · 2025
0.80
4
DNA methylation at DLGAP2 and risk for relapse in alcohol dependence during acamprosate treatment.
PMID: 38364647
Drug Alcohol Depend · 2024
0.70
5
Cross-Species Analyses Identify Dlgap2 as a Regulator of Age-Related Cognitive Decline and Alzheimer's Dementia.
PMID: 32877673
Cell Rep · 2020
0.60