HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DLG3
discs large MAGUK scaffold protein 3
Chromosome X Β· Xq13.1
NCBI Gene: 1741Ensembl: ENSG00000082458.13HGNC: HGNC:2902UniProt: Q59FY1
115PubMed Papers
21Diseases
0Drugs
40Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
GO:0005615protein bindingphosphatase bindingkinase bindingX-linked non-syndromic intellectual disabilitygenetic disorderX-linked intellectual disability, Siderius typenon-syndromic X-linked intellectual disability
✦AI Summary

DLG3 (discs large MAGUK scaffold protein 3), also known as SAP102, is an X-linked scaffolding protein essential for synaptic organization and plasticity in the central nervous system 1. It functions as a site-specific organizational center clustering key synaptic components necessary for learning and memory by organizing excitatory synapses and their associated signaling molecules 2. DLG3 mediates its effects through interactions with NMDA receptors and regulates postsynaptic membrane receptor levels and localization 1. Hemizygous loss-of-function variants in DLG3 cause X-linked intellectual developmental disorder 90 (XLID90), a syndromic neurodevelopmental disorder frequently associated with morphological features and intellectual disability 3. DLG3 mutations have also been implicated in autism spectrum disorder and schizophrenia 41. Additionally, abnormal DLG3 expression links to psychiatric and neurodegenerative conditions including bipolar disorder, major depression, and Alzheimer's disease 1. Beyond neurology, DLG3 influences cancer biology. High DLG3 expression correlates with decreased survival in breast cancer and is associated with tumor progression 5. In glioma, COP1-mediated ubiquitination of DLG3 facilitates cell proliferation, invasion, and migration 6. DLG3 also regulates signaling pathways including PI3K/AKT and Hippo pathways relevant to tumorigenesis 1.

Sources cited
1
DLG3/SAP102 is essential for excitatory synapse organization, clustering key synaptic components for learning and memory, and involved in XLID, ASD, schizophrenia, and cancer pathways
PMID: 39638232
2
DLG3 loss-of-function variants cause X-linked intellectual developmental disorder 90 with association to morphological features, extending to syndromic neurodevelopmental disorder
PMID: 40983642
3
DLG3 encodes neuroendocrine Dlg, a MAGUK family protein critical for synaptogenesis and acting as organizational center for membrane proteins and cytoskeletal signaling
PMID: 9598320
4
DLG3 identified as potentially pathogenic candidate gene in autism spectrum disorder cohort with diverse ancestry
PMID: 39632905
5
High DLG3 expression in breast cancer tissues correlates with decreased survival rate and pathologic stage
PMID: 31271664
6
COP1 ubiquitinates DLG3 protein to facilitate glioma cell proliferation, invasion, and migration
PMID: 37356109
Disease Associationsβ“˜21
X-linked non-syndromic intellectual disabilityOpen Targets
0.75Strong
genetic disorderOpen Targets
0.51Moderate
X-linked intellectual disability, Siderius typeOpen Targets
0.46Moderate
non-syndromic X-linked intellectual disabilityOpen Targets
0.46Moderate
Intellectual disabilityOpen Targets
0.44Moderate
neurodegenerative diseaseOpen Targets
0.36Weak
Neurodevelopmental disorderOpen Targets
0.12Weak
epilepsyOpen Targets
0.12Weak
breast cancerOpen Targets
0.10Weak
oral squamous cell carcinomaOpen Targets
0.08Suggestive
12q14 microdeletion syndromeOpen Targets
0.06Suggestive
osteoporosisOpen Targets
0.05Suggestive
postmenopausal osteoporosisOpen Targets
0.05Suggestive
pyknoachondrogenesisOpen Targets
0.05Suggestive
melorheostosisOpen Targets
0.05Suggestive
Dacryocystitis - osteopoikilosisOpen Targets
0.05Suggestive
dacryocystitis-osteopoikilosis syndromeOpen Targets
0.05Suggestive
osteomesopyknosisOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.04Suggestive
gnathodiaphyseal dysplasiaOpen Targets
0.04Suggestive
Intellectual developmental disorder, X-linked 90UniProt
Pathogenic Variants40
NM_021120.4(DLG3):c.2266C>T (p.Arg756Ter)Pathogenic
not provided|Intellectual disability, X-linked 90
β˜…β˜…β˜†β˜†2025β†’ Residue 756
NM_021120.4(DLG3):c.649C>T (p.Arg217Ter)Pathogenic
not provided|Intellectual disability, X-linked 90
β˜…β˜…β˜†β˜†2024β†’ Residue 217
NM_021120.4(DLG3):c.2035C>T (p.Arg679Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 679
NM_021120.4(DLG3):c.159del (p.Tyr54fs)Pathogenic
not provided|Intellectual disability, X-linked 90
β˜…β˜…β˜†β˜†2022β†’ Residue 54
NM_021120.4(DLG3):c.631C>T (p.Arg211Ter)Pathogenic
Inborn genetic diseases|DLG3-related disorder|not provided
β˜…β˜…β˜†β˜†2020β†’ Residue 211
NM_021120.4(DLG3):c.1513_1519del (p.Tyr505fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 505
NM_021120.4(DLG3):c.592C>T (p.Arg198Trp)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 198
NM_021120.4(DLG3):c.1373C>G (p.Ser458Ter)Pathogenic
Intellectual disability, X-linked 90|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 458
NM_021120.4(DLG3):c.985+5G>ALikely pathogenic
Intellectual disability, X-linked 90|not provided
β˜…β˜†β˜†β˜†2025
NM_021120.4(DLG3):c.1349_1350del (p.Ala450fs)Pathogenic
Intellectual disability, X-linked 90
β˜…β˜†β˜†β˜†2025β†’ Residue 450
NM_021120.4(DLG3):c.131dup (p.Asn45fs)Likely pathogenic
Intellectual disability, X-linked 90
β˜…β˜†β˜†β˜†2025β†’ Residue 45
NC_000023.11:g.(70500990_70502096)_(70502336_?)delLikely pathogenic
Intellectual disability, X-linked 90
β˜…β˜†β˜†β˜†2025
NM_021120.4(DLG3):c.691A>T (p.Lys231Ter)Likely pathogenic
Intellectual disability, X-linked 90
β˜…β˜†β˜†β˜†2025β†’ Residue 231
NM_021120.4(DLG3):c.1015dup (p.Ser339fs)Likely pathogenic
Intellectual disability, X-linked 90
β˜…β˜†β˜†β˜†2025β†’ Residue 339
NM_021120.4(DLG3):c.1619_1628del (p.Asp540fs)Likely pathogenic
Intellectual disability, X-linked 90
β˜…β˜†β˜†β˜†2025β†’ Residue 540
NM_021120.4(DLG3):c.2371G>T (p.Glu791Ter)Likely pathogenic
Intellectual disability, X-linked 90
β˜…β˜†β˜†β˜†2025β†’ Residue 791
NM_021120.4(DLG3):c.1462dup (p.Ser488fs)Likely pathogenic
Intellectual disability, X-linked 90
β˜…β˜†β˜†β˜†2025β†’ Residue 488
NM_021120.4(DLG3):c.1302+5G>ALikely pathogenic
Intellectual disability, X-linked 90
β˜…β˜†β˜†β˜†2025
NM_021120.4(DLG3):c.791del (p.Gly264fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 264
NM_021120.4(DLG3):c.2095_2097del (p.Asp699del)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 699
View on ClinVar β†—
Related Genes
NLGN2Protein interaction100%NLGN1Protein interaction100%NLGN3Protein interaction100%NLGN4YProtein interaction100%NLGN4XProtein interaction100%GRIN1Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Ovary
64%
Heart
50%
Lung
26%
Bone Marrow
13%
Liver
9%
Gene Interaction Network
Click a node to explore
DLG3NLGN2NLGN1NLGN3NLGN4YNLGN4XGRIN1
PROTEIN STRUCTURE
Preparing viewer…
PDB2FE5 Β· 1.10 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.07Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.02 [0.01–0.07]
RankingsWhere DLG3 stands among ~20K protein-coding genes
  • #4,111of 20,598
    Most Researched115 Β· top quartile
  • #1,537of 5,498
    Most Pathogenic Variants40
  • #18of 17,882
    Most Constrained (LOEUF)0.07 Β· top 1%
Genes detectedDLG3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Neuronal Activity Promotes Glioma Progression by Inducing Proneural-to-Mesenchymal Transition in Glioma Stem Cells.
PMID: 37963207
Cancer Res Β· 2024
1.00
2
Further phenotypical delineation of DLG3-related neurodevelopmental disorders.
PMID: 40983642
Eur J Hum Genet Β· 2025
0.90
3
Multifaceted roles of DLG3/SAP102 in neurophysiology, neurological disorders and tumorigenesis.
PMID: 39638232
Neuroscience Β· 2025
0.80
4
Parallel mRNA and microRNA profiling of HEV71-infected human neuroblastoma cells reveal the up-regulation of miR-1246 in association with DLG3 repression.
PMID: 24739954
PLoS One Β· 2014
0.70
5
DLG3, the gene encoding human neuroendocrine Dlg (NE-Dlg), is located within the 1.8-Mb dystonia-parkinsonism region at Xq13.1.
PMID: 9598320
Genomics Β· 1998
0.60