DLG4 (Disks large homolog 4) variants and mutations

DLG4 (also known as Disks large homolog 4) is a human protein-coding gene encoding a disks large homolog 4 protein. It organizes glutamate receptors, signaling enzymes, and cytoskeletal proteins at excitatory postsynaptic densities, making it central to synaptic transmission and plasticity. Haploinsufficiency can cause a neurodevelopmental disorder with intellectual disability, autism-related features, and sometimes epilepsy. This analysis covers 892 DLG4 variants and mutations. Of these, 70% have computational variant effect predictions. Disease context includes intellectual developmental disorder 62, hereditary disease, and neurodegenerative disease. Example DLG4 variants include M1?, C3S, and V7L.

Variant analysis overview

Gene: DLG4
Protein: Disks large homolog 4
UniProt accession: P78352
Organism: Homo sapiens
Variants analyzed: 892
Variant scope: all variants
Completed: 2026-08-20

Variant and mutation evidence

Variant composition: 664 unspecified-consequence records; 64 synonymous variants; 139 missense variants; 4 stop-gained variants; 1 in-frame deletions; 3 splice-region variants; 8 frameshift variants; 9 substitution
Prediction scores: 628 variants have prediction scores (70% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: intellectual developmental disorder 62, hereditary disease, neurodegenerative disease, Intellectual disability, complex neurodevelopmental disorder, Neurodevelopmental delay, Disproportionate tall stature, autoimmune disorder of central nervous system, marfanoid habitus and intellectual disability, intellectual developmental disorder with paroxysmal dyskinesia or seizures, autism spectrum disorder, intellectual disability-epilepsy-extrapyramidal syndrome.

Protein structure and variant hotspots

Protein features: 5 domains; 15 post-translational modification sites.
Structural context: 629 variants have structural context.
PTM context: 20 variants overlap post-translational modification sites.
Experimental data: 90 protein positions have experimental scores. Source: DLG4 PDZ domain domainome 1.0.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable DLG4 variants

Examples include M1?, C3S, V7L, T9N, Y12C, R13C, R13Q, Y14S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

DLG4 analysis run — DLG4 (892 variants) — completed 2026-08-20