KIF5A (Kinesin heavy chain isoform 5A) variants and mutations

KIF5A (also known as Kinesin heavy chain isoform 5A) is a human protein-coding gene encoding a kinesin heavy chain isoform 5A protein. It drives anterograde transport of organelles and proteins along axonal microtubules and is especially important in long motor neurons. Pathogenic variants can cause hereditary spastic paraplegia, axonal Charcot-Marie-Tooth disease, or amyotrophic lateral sclerosis depending on the affected region and mechanism. This analysis covers 1,237 KIF5A variants and mutations. Of these, 71% have computational variant effect predictions. Disease context includes hereditary spastic paraplegia 10, Autosomal dominant spastic paraplegia type 10, and amyotrophic lateral sclerosis. Example KIF5A variants include M1I, A2E, and A2G.

Variant analysis overview

Gene: KIF5A
Protein: Kinesin heavy chain isoform 5A
UniProt accession: Q12840
Organism: Homo sapiens
Variants analyzed: 1237
Variant scope: all variants
Completed: 2026-08-22

Variant and mutation evidence

Variant composition: 1,109 unspecified-consequence records; 59 synonymous variants; 58 missense variants; 1 in-frame insertions; 3 splice-region variants; 2 stop-gained variants; 3 frameshift variants; 3 substitution
Prediction scores: 873 variants have prediction scores (71% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: hereditary spastic paraplegia 10, Autosomal dominant spastic paraplegia type 10, amyotrophic lateral sclerosis, myoclonus, intractable, neonatal, hereditary spastic paraplegia, Spastic paraplegia, inherited neurodegenerative disorder, Intellectual disability, autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation, demyelinating polyneuropathy, familial infantile myoclonic epilepsy, Charcot-Marie-Tooth disease type 2.

Protein structure and variant hotspots

Protein features: 1 domains; 1 binding sites; 2 post-translational modification sites.
Structural context: 434 variants have structural context.
PTM context: 6 variants overlap post-translational modification sites.

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 KIF5A variants

Examples include M1I, A2E, A2G, A2K, A2T, A2V, E3Q, E3E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

KIF5A analysis run — KIF5A (1,237 variants) — completed 2026-08-22