DLG1

Chr 3

discs large MAGUK scaffold protein 1

Also known as: DLGH1, SAP-97, SAP97, hdlg

NCBI Gene: 1739 ENSG00000075711 UniProt: Q12959 OMIM: 601014

This gene encodes an essential multidomain scaffolding protein that recruits channels, receptors and signaling molecules to discrete plasma membrane domains and maintains cell-cell adhesion in polarized cells. Mutations cause intellectual disability with seizures, and the gene shows autosomal dominant inheritance. The gene is highly constrained against loss-of-function mutations, reflecting its critical role in normal development and neuronal function.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a multi-domain scaffolding protein that is required for normal development. This protein may have a role in septate junction formation, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. A multitude of transcript variants deriving from alternative splicing and the use of multiple alternate promoter have been observed, including some splice variants that may be specific to brain and other tissues. An upstream uORF may regulate translation at some splice variants of this gene. [provided by RefSeq, Sep 2018]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.29

Clinical Summary— DLG1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

101 VUS of 166 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.994

Z-score 5.93

OE 0.17 (0.10–0.29)

Highly constrained

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

Missense Constraint?

1.50Z-score

OE missense 0.81 (0.75–0.88)

403 obs / 496.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.17 (0.10–0.29)

0≤0.351.4

Missense OE?0.81 (0.75–0.88)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 10 / 59.3Missense obs/exp: 403 / 496.8Syn Z: 1.54

This gene — mechanism propensity

0.4190th %ile

GOF

0.6150th %ile

LOF

0.70top 10%

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

LOFprediction above median · LOEUF 0.29

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

ClinVar Variant Classifications

166 submitted variants in ClinVar

ClinVar

Classification Summary

VUS101

Likely Benign18

Benign9

101

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	100	1	0	101
Likely Benign	5	6	7	18
Benign	4	1	4	9
Total	109	8	11	128

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

89 pathogenic / likely-pathogenic (of 118) ClinVar copy-number / structural variants overlap DLG1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →