DSCAM

Chr 21

DS cell adhesion molecule

Also known as: CHD2, CHD2-42, CHD2-52

DSCAM encodes a cell adhesion molecule that mediates neuronal self-avoidance, axon guidance, and lamina-specific synaptic connections in retinal and spinal cord development. Mutations cause autosomal dominant intellectual disability with behavioral abnormalities and seizures, typically presenting in early childhood. This gene is extremely intolerant to loss-of-function variants, indicating that proper dosage is critical for normal neurodevelopment.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.19
Clinical SummaryDSCAM
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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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 8.07
OE 0.11 (0.070.19)
Highly constrained

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

Missense Constraint
3.22Z-score
OE missense 0.74 (0.700.78)
889 obs / 1203.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.11 (0.070.19)
00.351.4
Missense OE0.74 (0.700.78)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 11 / 96.5Missense obs/exp: 889 / 1203.6Syn Z: -1.21
DN
0.5378th %ile
GOF
0.5171th %ile
LOF
0.68top 25%

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

LOFprediction above median · 1 literature citation · LOEUF 0.19

Literature Evidence

LOFStudy sequences 189 autism risk genes in a 1,543 Chinese ASD probands (1,045 from trios). Two de novo DSCAM disrupting variants (defined as nonsense, frameshift or splice site) in 1,086 Chinese ASD trios. Also one maternally inherited DSCAM disrupting variant (maternal phenotype unclear). Also, 20 mPMID:27824329

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

DSCAM · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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