DLG4

Chr 17p13.1

discs large MAGUK scaffold protein 4

Aliases:: PSD-95, PSD95, SAP90, SAP-90
MANE:: ENST00000399506.9

OMIM: 602887 ↗NCBI: 1742 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

DLG4 · P78352

v62025-08-01

Predicted Aligned Error matrix for DLG4 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

77.6/ 100

Confident

724 residues

Confidence breakdown

Very high(≥ 90)51%
Confident(70–90)23%
Low(50–70)6%
Very low(< 50)20%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Ataxia and cerebellar anomalies - narrow panel
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

intellectual developmental disorder 62
0.77
hereditary disease
0.52
neurodegenerative disease
0.51
Intellectual disability
0.50
complex neurodevelopmental disorder
0.46
Neurodevelopmental delay
0.43
Disproportionate tall stature
0.37
autoimmune disorder of central nervous system
0.37
marfanoid habitus and intellectual disability
0.36
intellectual developmental disorder with paroxysmal dyskinesia or seizures
0.35

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Disks large homolog 4

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)