SHANK1
Chr 19SH3 and multiple ankyrin repeat domains 1
Also known as: SPANK-1, SSTRIP, synamon
This protein functions as a scaffold in the postsynaptic density of excitatory synapses, interconnecting glutamate receptors with the actin cytoskeleton and organizing dendritic spine structure. Deletions cause autism spectrum disorder, particularly in males, with X-linked inheritance. The gene is highly constrained against loss-of-function variation (pLI >0.99), indicating that such variants are likely to be pathogenic.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
200 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 3 | 0 | 0 | 0 | 3 |
Likely Pathogenic | 4 | 0 | 0 | 0 | 4 |
VUS | 0 | 165 | 1 | 0 | 166 |
Likely Benign | 0 | 21 | 2 | 3 | 26 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 7 | 186 | 3 | 3 | 199 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SHANK1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools