DLG4

Chr 17

discs large MAGUK scaffold protein 4

Also known as: MRD62, PSD95, SAP-90, SAP90

NCBI Gene: 1742 ENSG00000132535 UniProt: P78352

The DLG4 protein heteromultimerizes with DLG2 to form postsynaptic scaffolds that cluster NMDA receptors, potassium channels, and associated signaling proteins at synapses. Loss-of-function mutations cause autosomal dominant intellectual developmental disorder. The high constraint scores (pLI 0.999, LOEUF 0.238) indicate this gene is highly intolerant to loss-of-function variants, consistent with the dominant inheritance pattern where haploinsufficiency disrupts synaptic function.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal dominant 62

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — DLG4