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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DLGAP4
DLG associated protein 4
Chromosome 20 · 20q11.23
NCBI Gene: 22839Ensembl: ENSG00000080845.19HGNC: HGNC:24476UniProt: A0A0B4J2C2
47PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmolecular adaptor activitymodulation of chemical synaptic transmissionglutamatergic synapseAbnormality of the skeletal systembasal cell carcinomaskin neoplasmgram-negative bacterial infections
✦AI Summary

DLGAP4 (DLG associated protein 4) is a synaptic scaffold protein that plays critical roles in both neuronal development and synapse organization. The protein functions as an adapter linking ion channels to the postsynaptic cytoskeleton and may induce enrichment of PSD-95/SAP90 at the plasma membrane 1. During cortical development, DLGAP4 is strongly expressed in the ventricular zone and interacts with key proteins including EML1, where it regulates progenitor cell dynamics, morphology, proliferation, and neuronal migration 1. The protein is essential for organizing radial glial cell adherens junction components and actin cytoskeleton dynamics at the apical domain 1. Beyond its developmental roles, DLGAP4 serves as a substrate for calpain-5, a calcium-activated protease involved in synaptic protein processing 2. Clinically, DLGAP4 dysfunction is associated with neurological disorders, as chr20 translocations disrupting the gene co-segregate with cerebellar ataxia and cause epigenetic remodeling leading to dysregulated expression 3. Circular RNAs derived from DLGAP4 have emerged as potential biomarkers for acute ischemic stroke 4 and are involved in diabetic kidney disease progression through miRNA sponging mechanisms 5. The gene also shows altered expression in various cancers, suggesting broader pathological roles beyond the nervous system 6.

Sources cited
1
DLGAP4 functions in cortical development, ventricular zone expression, and neuronal migration
PMID: 35585091
2
Chromosomal translocations disrupting DLGAP4 cause cerebellar ataxia and epigenetic dysregulation
PMID: 24986922
3
DLGAP4 serves as a proteolytic substrate for calpain-5
PMID: 40650235
4
Circular RNAs from DLGAP4 are potential biomarkers for acute ischemic stroke
PMID: 37186176
5
Exosomal circ_DLGAP4 promotes diabetic kidney disease through miRNA sponging
PMID: 33230102
6
DLGAP4 expression is altered in hepatocellular carcinoma
PMID: 36396671
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.33Weak
basal cell carcinomaOpen Targets
0.32Weak
skin neoplasmOpen Targets
0.31Weak
gram-negative bacterial infectionsOpen Targets
0.28Weak
skin diseaseOpen Targets
0.26Weak
actinic keratosisOpen Targets
0.24Weak
cutaneous melanomaOpen Targets
0.24Weak
skin cancerOpen Targets
0.23Weak
joint diseaseOpen Targets
0.22Weak
exostosisOpen Targets
0.16Weak
squamous cell carcinomaOpen Targets
0.14Weak
supraventricular ectopyOpen Targets
0.14Weak
sleep apneaOpen Targets
0.13Weak
ovarian dysfunctionOpen Targets
0.13Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.08Suggestive
lipomaOpen Targets
0.05Suggestive
childhood disintegrative disorderOpen Targets
0.04Suggestive
15q11q13 microduplication syndromeOpen Targets
0.03Suggestive
response to statinOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DLG4Protein interaction99%SHANK3Protein interaction98%SHANK2Protein interaction97%DLGAP3Protein interaction86%DLG2Protein interaction77%DLG3Protein interaction77%
Tissue Expression6 tissues
Lung
100%
Brain
99%
Ovary
78%
Heart
74%
Liver
57%
Bone Marrow
9%
Gene Interaction Network
Click a node to explore
DLGAP4DLG4SHANK3SHANK2DLGAP3DLG2DLG3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9Y2H0
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.33Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.22 [0.15–0.33]
RankingsWhere DLGAP4 stands among ~20K protein-coding genes
  • #9,195of 20,598
    Most Researched47
  • #1,394of 17,882
    Most Constrained (LOEUF)0.33 · top 10%
Genes detectedDLGAP4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Novel role of the synaptic scaffold protein Dlgap4 in ventricular surface integrity and neuronal migration during cortical development.
PMID: 35585091
Nat Commun · 2022
1.00
2
Epigenetic remodelling and dysregulation of DLGAP4 is linked with early-onset cerebellar ataxia.
PMID: 24986922
Hum Mol Genet · 2014
0.90
3
DLGAP4 acts as an effective prognostic predictor for hepatocellular carcinoma and is closely related to tumour progression.
PMID: 36396671
Sci Rep · 2022
0.80
4
Serum Circ-DLGAP4 and miR-9 as Potential Biomarkers in Pancreatic Cancer.
PMID: 40709841
J Clin Lab Anal · 2025
0.70
5
Exosomal circ_DLGAP4 promotes diabetic kidney disease progression by sponging miR-143 and targeting ERBB3/NF-κB/MMP-2 axis.
PMID: 33230102
Cell Death Dis · 2020
0.60