DLGAP2

Chr 8

DLG associated protein 2

Also known as: C8orf68, DAP2, ERICH1-AS1, SAPAP2

The protein is a membrane-associated protein that organizes synapses and facilitates signaling in neuronal cells. Loss-of-function mutations cause neurodevelopmental disorders with intellectual disability and autism spectrum features, inherited in an autosomal recessive pattern. The high constraint scores (pLI 0.999, LOEUF 0.199) indicate the gene is highly intolerant to loss-of-function variants, consistent with severe developmental phenotypes when both alleles are affected.

Summary from RefSeq, UniProt, Mechanism
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0
Active trials
9
Pubs (1 yr)
129
P/LP submissions
0%
P/LP missense
0.20
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryDLGAP2
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADLimited

Limited evidence — not for standalone diagnostic reporting

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
128 unique Pathogenic / Likely Pathogenic· 224 VUS of 410 total submissions
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GeneReview available — DLGAP2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.20LOEUF
pLI 1.000
Z-score 5.35
OE 0.08 (0.030.20)
Highly constrained

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

Missense Constraint
-1.00Z-score
OE missense 1.11 (1.041.18)
711 obs / 640.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.08 (0.030.20)
00.351.4
Missense OE1.11 (1.041.18)
00.61.4
Synonymous OE1.40
01.21.6
LoF obs/exp: 3 / 39.1Missense obs/exp: 711 / 640.1Syn Z: -5.48
DN
0.5477th %ile
GOF
0.5269th %ile
LOF
0.73top 10%

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

LOFprediction above median · LOEUF 0.20

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

410 submitted variants in ClinVar

Classification Summary

Pathogenic120
Likely Pathogenic8
VUS224
Likely Benign31
Benign13
Conflicting2
120
Pathogenic
8
Likely Pathogenic
224
VUS
31
Likely Benign
13
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
120
0
120
Likely Pathogenic
0
0
8
0
8
VUS
1
140
83
0
224
Likely Benign
0
5
15
11
31
Benign
0
5
4
4
13
Conflicting
2
Total115023015398

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

View in ClinVar →

Protein Context — Lollipop Plot

DLGAP2 · 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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