SPAST (Spastin) variants and mutations

SPAST (also known as Spastin) is a human protein-coding gene encoding a spastin protein. It severs microtubules and remodels the axonal cytoskeleton, enabling organelle transport and maintenance of very long corticospinal axons. Dominant loss-of-function variants are the most common cause of hereditary spastic paraplegia, classically SPG4. This analysis covers 1,384 SPAST variants and mutations. Of these, 80% have computational variant effect predictions. Disease context includes Autosomal dominant spastic paraplegia type 4, hereditary spastic paraplegia 4, and hereditary spastic paraplegia. Example SPAST variants include M1I, M1V, and N2S.

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, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable SPAST variants

Examples include M1I, M1V, N2S, S3F, S3Y, S3S, P4A, P4L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.