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SPG4

Chr 2AD

spastin

Also known as: ADPSP, FSP2, SPG4

The protein is an ATP-dependent microtubule severing enzyme that cuts polyglutamylated microtubules and is critical for maintaining complex microtubule arrays in axons, cell division, and membrane trafficking between cellular compartments. Mutations cause spastic paraplegia 4, the most common form of autosomal dominant hereditary spastic paraplegia, which primarily affects the corticospinal tracts and lower extremities. This follows autosomal dominant inheritance with high penetrance but variable expressivity.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD1 OMIM phenotype
Clinical SummarySPG4
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — SPG4
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (2)

ensembl: Error: Ensembl fetch failed: 400 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/SPG4?content-type=application/json&expand=1

gnomad: Error: Gene not found

Population Genetics & Constraint

Constraint data not available from gnomAD.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SPG4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic, structural and clinical analysis of spastic paraplegia 4.
Varghaei P et al.·Parkinsonism Relat Disord
2022
Movement disorders in hereditary spastic paraplegias.
Pedroso JL et al.·Arq Neuropsiquiatr
2023Review
Corticospinal tract and motor cortex degeneration in pure hereditary spastic paraparesis type 4 (SPG4).
Navas-Sánchez FJ et al.·Amyotroph Lateral Scler Frontotemporal Degener
2022
Top 5 results · since 2015Search PubMed ↗