SHANK1 (Q9Y566) variants and mutations

SHANK1 (also known as Q9Y566) is a human protein-coding gene encoding a SH3 and multiple ankyrin repeat domains protein 1 protein. It organizes postsynaptic protein networks at excitatory synapses and links glutamate receptors to signaling and cytoskeletal machinery. Rare disruptive variants have been associated with neurodevelopmental and psychiatric phenotypes, although penetrance and causal evidence vary. This analysis covers 2,966 SHANK1 variants and mutations. Of these, 97% have computational variant effect predictions. Disease context includes Intellectual disability, neurodevelopmental disorder, and autism. Example SHANK1 variants include H3Q, H3R, and S4I.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable SHANK1 variants

Examples include H3Q, H3R, S4I, P5T, A6P, A6S, A6T, A6V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.