DLG2

Chr 11

discs large MAGUK scaffold protein 2

Also known as: PPP1R58, PSD-93, PSD93, chapsyn-110

NCBI Gene: 1740 ENSG00000150672 UniProt: Q15700

The encoded protein is a postsynaptic scaffolding protein that regulates surface expression of NMDA receptors and clustering of receptors, ion channels, and signaling proteins at excitatory synapses. Mutations cause intellectual disability with onset in infancy or early childhood, and the gene shows high constraint against loss-of-function variants (LOEUF 0.338). Inheritance follows an autosomal dominant pattern.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. The encoded protein forms a heterodimer with a related family member that 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. Additional transcript variants have been described, but their full-length nature is not known. [provided by RefSeq, Dec 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.34

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.708

Z-score 5.71

OE 0.21 (0.14–0.34)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.08Z-score

OE missense 0.75 (0.69–0.81)

400 obs / 535.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.21 (0.14–0.34)

0≤0.351.4

Missense OE?0.75 (0.69–0.81)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 13 / 61.2Missense obs/exp: 400 / 535.2Syn Z: 0.76

Background carrier burden — how many people carry a rare variant somewhere in DLG2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 43

1,524 rare PASS variants

Rare truncating (LoF)

1 in 570

181 rare PASS variants

Rare synonymous (reference)

1 in 67

621 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DLG2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 56	1 in 700
South Asian	~43k	1 in 53	1 in 370
Remaining (unassigned)	~30k	1 in 42	1 in 560
European (Finnish)	~27k	1 in 150	1 in 2,400
Admixed American	~22k	1 in 56	1 in 460
African / African American	~21k	1 in 56	1 in 910
East Asian	~20k	1 in 59	1 in 380
Ashkenazi Jewish	~13k	1 in 130	none seen
Middle Eastern	~2,884	1 in 46	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 19 of 26 coding exons well covered in gnomAD exomes; exons 3, 5, 8, 9, 22 and 2 more marginal. Genomes: all 26.? see exons ↓