DLG3

Chr XXLR

discs large MAGUK scaffold protein 3

Also known as: MRX, MRX90, NEDLG, PPP1R82, SAP102, XLID90, XLMR

NCBI Gene: 1741 ENSG00000082458 UniProt: Q13368 OMIM: 300189

This protein is required for learning through its role in synaptic plasticity following NMDA receptor signaling and clusters NMDA receptors at excitatory synapses. Mutations cause X-linked intellectual developmental disorder. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.09) and follows X-linked recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the membrane-associated guanylate kinase protein family. The encoded protein may play a role in clustering of NMDA receptors at excitatory synapses. It may also negatively regulate cell proliferation through interaction with the C-terminal region of the adenomatosis polyposis coli tumor suppressor protein. Mutations in this gene have been associated with X-linked cognitive disability. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]

OMIM ResearchGenerating clinical summary…

LOFmechanismXLRLOEUF 0.091 OMIM phenotype

Clinical Summary— DLG3

🧬

Gene-Disease Validity (ClinGen)

non-syndromic X-linked intellectual disability · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.09LOEUF

pLI 1.000

Z-score 5.35

OE 0.00 (0.00–0.09)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.88Z-score

OE missense 0.56 (0.49–0.63)

186 obs / 333.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.09)

0≤0.351.4

Missense OE?0.56 (0.49–0.63)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 0 / 33.3Missense obs/exp: 186 / 333.9Syn Z: 0.70

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveDLG3-related intellectual developmental disorderLOFXLR

This gene — mechanism propensity

0.4091th %ile

GOF

0.5465th %ile

LOF

0.76top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.09 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.