DLGAP3

Chr 1

DLG associated protein 3

Also known as: DAP3, SAPAP3, SPAPA3

NCBI Gene: 58512 ENSG00000116544 UniProt: O95886 OMIM: 611413

DLGAP3 encodes a synaptic scaffold protein that organizes postsynaptic density complexes and links ion channels to the cytoskeleton at glutamatergic and cholinergic synapses. Mutations cause autosomal dominant intellectual disability with autism spectrum disorder features. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.14), indicating intolerance to protein truncation.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable PDZ domain binding activity; molecular adaptor activity; and scaffold protein binding activity. Predicted to be involved in modulation of chemical synaptic transmission and protein-containing complex assembly. Predicted to be located in plasma membrane. Predicted to be active in several cellular components, including cholinergic synapse; glutamatergic synapse; and neuromuscular junction. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.14

Clinical Summary— DLGAP3

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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.

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ClinVar Variants

1 VUS of 25 total submissions

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?

0.14LOEUF

pLI 1.000

Z-score 5.32

OE 0.03 (0.01–0.14)

Highly constrained

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

Missense Constraint?

2.63Z-score

OE missense 0.70 (0.64–0.76)

415 obs / 595.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.14)

0≤0.351.4

Missense OE?0.70 (0.64–0.76)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 1 / 35.0Missense obs/exp: 415 / 595.4Syn Z: 0.03

This gene — mechanism propensity

0.4289th %ile

GOF

0.4283th %ile

LOF

0.82top 5%

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

LOFprediction above median · LOEUF 0.14

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

25 submitted variants in ClinVar

ClinVar

Classification Summary

VUS1

Likely Benign6

Benign5

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	1	0	1
Likely Benign	1	2	3	6
Benign	0	0	5	5
Total	1	3	8	12

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap DLGAP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →