Protein / target

Disks large homolog 4

Encoded byDLG4P78352Homo sapiensSwiss-Prot

UniProt: P78352 Ensembl: ENSG00000132535 HGNC: HGNC:2903 NCBI Gene: 1742

Small-molecule tractable

Druggability

High-Quality Ligand

Research papers

Protein at a glance

Biological role

Protein-macromolecule adaptor

Strongest disease association

Genetic Diseases, Inborn

Via encoding gene DLG4 · Genetic evidence · score 0.85

Research activity

Emerging research

7 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins.

View complete UniProt function annotation

Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression (By similarity). Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (PubMed:26334723)

Subcellular location

Cell membranePostsynaptic densitySynapseCytoplasmCell projection, axonCell projection, dendritic spineCell projection, dendritePresynapse

Domains and Gene Ontology detail (71)

Domains & features

PDZ 1PDZ 2PDZ 3SH3Guanylate kinase-like

Gene Ontology

Cadherens junction
CAMPA glutamate receptor complex
Ccell junction
Ccerebellar mossy fiber
Ccortical cytoskeleton
Ccytoplasm
Ccytosol
Cdendrite cytoplasm
Cdendritic spine
Cendocytic vesicle membrane
Cendoplasmic reticulum
Cexcitatory synapse

724 aa · 80 kDa · 3 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Excitatory neurotransmissionGOInhibitory neurotransmissionUniProtCell adhesionGO

View supporting evidence

Excitatory neurotransmission

·excitatory synapse
·glutamatergic synapse
·positive regulation of excitatory postsynaptic potential

Inhibitory neurotransmission

·Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synapt…

Cell adhesion

·cell junction
·cell-cell adhesion

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene DLG4

Gene-level evidence surfaced through the gene DLG4that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Genetic Diseases, Inborn

0.85Well supported

Genetic evidence dominant · Open Targets 0.52

Complex neurodevelopmental disorder

0.61Moderately supported

Genetic evidence dominant · Open Targets 0.46

Neurodegenerative Diseases

0.36Preliminary

Pathway evidence dominant · Open Targets 0.51 · no direct causal or clinical evidence

Autoimmune disorder of central nervous system

0.24Preliminary

Pathway evidence dominant · Open Targets 0.37 · no direct causal or clinical evidence

View evidence synthesis (4)

Genetic Diseases, InbornWell supported

0.85

agreement 0.71–0.99

Genetic100%Literature0%

Open Targets aggregate 0.52 · 2 independent evidence families

Complex neurodevelopmental disorderModerately supported

0.61

agreement 0.49–0.73

Genetic100%Genetic literaturedup

Open Targets aggregate 0.46 · 1 independent evidence family · 1 not counted as duplicate

Neurodegenerative DiseasesPreliminary

0.36

agreement 0.19–0.54

Pathway86%Literature14%

Open Targets aggregate 0.51 · 2 independent evidence families · no direct causal or clinical evidence

Autoimmune disorder of central nervous systemPreliminary

0.24

agreement 0.01–0.47

Pathway100%

Open Targets aggregate 0.37 · 1 independent evidence family · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Genetic Diseases, Inborn0.52

Neurodegenerative Diseases0.51

Complex neurodevelopmental disorder0.46

Autoimmune disorder of central nervous system0.37

Tractability

Small molecules — Emerging

Feasibility evidence (high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)

SM · High-Quality LigandAB · UniProt loc high confAB · GO CC high confPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.