DLGAP1

Chr 18

DLG associated protein 1

Also known as: DAP-1, DAP-1-ALPHA, DAP-1-BETA, DAP1, DLGAP1A, DLGAP1B, GKAP, SAPAP1

The protein functions as part of the postsynaptic scaffold in neuronal cells and serves as a structural constituent of the postsynaptic density at glutamatergic synapses. Mutations cause neurodevelopmental disorders with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.254), indicating that haploinsufficiency is likely not tolerated in the general population.

Summary from RefSeq, UniProt
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0
Active trials
11
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.25
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryDLGAP1
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.25LOEUF
pLI 0.999
Z-score 5.25
OE 0.12 (0.060.25)
Highly constrained

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

Missense Constraint
3.20Z-score
OE missense 0.64 (0.590.70)
403 obs / 628.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.12 (0.060.25)
00.351.4
Missense OE0.64 (0.590.70)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 5 / 41.5Missense obs/exp: 403 / 628.9Syn Z: 0.94
DN
0.4983th %ile
GOF
0.4973th %ile
LOF
0.76top 10%

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

LOFprediction above median · LOEUF 0.25

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DLGAP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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