KIF1A — kinesin family member 1A

17 sources retrieved · Most recent: April 2026 · Index updated 3 months ago

118PubMed Papers

#3,983 · top 20% of 19K genes

24Diseases

#184 · top 1.0%

0Drugs

204Pathogenic Variants

top 6%

OMIM Disease GeneHighly ConstrainedVariant-RichExperimental GO EvidenceSwiss-Prot Reviewed

identical protein bindingprotein bindingneuronal dense core vesiclemicrotubule bindingintellectual disability, autosomal dominant 9hereditary spastic paraplegia 30Autosomal recessive spastic paraplegia type 30neuropathy, hereditary sensory, type 2C

AI Summary

KIF1A is a plus-end-directed kinesin motor protein essential for anterograde axonal transport of synaptic vesicle precursors (SVPs) and dense core vesicles (DCVs) 1. The motor function is regulated through calcium-dependent interactions with CALM1, which increases vesicle motility, and through scaffolding protein interactions with PPFIA2 and TANC2 that recruit DCVs to synaptic sites [UniProt]. KIF1A specifically recognizes phosphatidylinositol 3,5-bisphosphate on precursor vesicles via coincident detection with active ARL8, directing cotransport of both synaptic vesicle and active zone proteins to developing presynapses 1. Pathogenic KIF1A variants cause multiple neurodegenerative disorders. Mutations in KIF1A represent a significant portion of hereditary spastic paraplegia (HSP) cases, particularly SPG30, affecting long central nervous system axons with maximal corticospinal tract degeneration 2 3. KIF1A also associates with hereditary sensory and autonomic neuropathy type 2 (HSAN2) and amyotrophic lateral sclerosis (ALS), where variants predominantly in the C-terminal cargo-binding region enhance SVP binding 4. KIF1A-associated neurological disorder (KAND) represents a severe neurodegenerative condition with heterozygous de novo missense variants, recently showing therapeutic responsiveness to allele-specific antisense oligonucleotide treatment 5. Beyond neurological disease, KIF1A unexpectedly promotes neuroendocrine differentiation in prostate cancer through OGT-mediated O-GlcNAcylation 6.

Sources cited

KIF1A transports synaptic vesicle and active zone proteins via recognition of PI(3,5)P2 and active ARL8

PMID: 37824668

KIF1A (SPG30) mediates axon transport; HSP involves motor-sensory axon degeneration in long CNS axons

PMID: 23897027

KIF1A mutations identified in >1% of hereditary spastic paraplegia cases in large diagnostic cohort

PMID: 34983064

KIF1A C-terminal variants associated with ALS; enhance binding of synaptic vesicle precursors

PMID: 36284339

KIF1A-associated neurological disorder (KAND) is ultrarare neurodegenerative disease responsive to antisense oligonucleotide therapy

PMID: 39122967

KIF1A promotes neuroendocrine prostate cancer differentiation via OGT-mediated O-GlcNAcylation

PMID: 39505875

Disease Associations24

intellectual disability, autosomal dominant 9Open Targets

0.85Strong

hereditary spastic paraplegia 30Open Targets

0.82Strong

Autosomal recessive spastic paraplegia type 30Open Targets

0.79Strong

neuropathy, hereditary sensory, type 2COpen Targets

0.77Strong

spastic paraplegia 30A, autosomal dominantOpen Targets

0.69Moderate

hereditary sensory and autonomic neuropathy type 2Open Targets

0.66Moderate

spastic paraplegia 30B, autosomal recessiveOpen Targets

0.58Moderate

neurodegenerative diseaseOpen Targets

0.58Moderate

hereditary spastic paraplegiaOpen Targets

0.54Moderate

genetic disorderOpen Targets

0.53Moderate

KIF1A related neurological disorderOpen Targets

0.51Moderate

lysosomal storage diseaseOpen Targets

0.50Moderate

Alzheimer diseaseOpen Targets

0.49Moderate

Spastic paraplegiaOpen Targets

0.49Moderate

Parkinson diseaseOpen Targets

0.48Moderate

multiple sclerosisOpen Targets

0.48Moderate

PEHO syndromeOpen Targets

0.47Moderate

syndromic intellectual disabilityOpen Targets

0.45Moderate

Intellectual disabilityOpen Targets

0.45Moderate

hereditary sensory and autonomic neuropathyOpen Targets

0.37Weak

NESCAV syndromeUniProt

Neuropathy, hereditary sensory, 2CUniProt

Spastic paraplegia 30A, autosomal dominantUniProt

Spastic paraplegia 30B, autosomal recessiveUniProt

Pathogenic Variants204

NM_001244008.2(KIF1A):c.761G>A (p.Arg254Gln)Pathogenic

★★☆☆2026→ Residue 254

NM_001244008.2(KIF1A):c.430G>T (p.Val144Phe)Likely pathogenic

Intellectual disability, autosomal dominant 9|Spastic paraplegia 30A, autosomal dominant;Intellectual disability, autosomal dominant 9

★★☆☆2026→ Residue 144

NM_001244008.2(KIF1A):c.4339C>T (p.Arg1447Ter)Pathogenic

not provided|Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9

★★☆☆2025→ Residue 1447

NM_001244008.2(KIF1A):c.646C>T (p.Arg216Cys)Pathogenic

★★☆☆2025→ Residue 216

NM_001244008.2(KIF1A):c.37C>T (p.Arg13Cys)Pathogenic

not provided|Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9|Intellectual disability, autosomal dominant 9|See cases|Hereditary spastic paraplegia 30;Intellectual disability, autosomal dominant 9|KIF1A related neurological disorder|Inborn genetic diseases|Hereditary spastic paraplegia 30

★★☆☆2025→ Residue 13

NM_001244008.2(KIF1A):c.1031C>T (p.Thr344Met)Pathogenic

Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30|Intellectual disability, autosomal dominant 9|Inborn genetic diseases

★★☆☆2025→ Residue 344

NM_001244008.2(KIF1A):c.914C>T (p.Pro305Leu)Pathogenic

Intellectual disability, autosomal dominant 9|not provided|Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9|Hereditary spastic paraplegia 30|Hereditary spastic paraplegia|KIF1A related neurological disorder

★★☆☆2025→ Residue 305

NM_001244008.2(KIF1A):c.31C>T (p.Arg11Trp)Pathogenic

Hereditary spastic paraplegia|Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9|Inborn genetic diseases|not provided|Hereditary spastic paraplegia 30

★★☆☆2025→ Residue 11

NM_001244008.2(KIF1A):c.757G>A (p.Glu253Lys)Pathogenic

Intellectual disability, autosomal dominant 9|not provided|Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30|Hereditary spastic paraplegia 30|KIF1A-related disorder

★★☆☆2025→ Residue 253

NM_001244008.2(KIF1A):c.2350C>T (p.Arg784Ter)Pathogenic

Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30|not provided|Hereditary spastic paraplegia 30

★★☆☆2025→ Residue 784

NM_001244008.2(KIF1A):c.206C>T (p.Ser69Leu)Pathogenic

Hereditary spastic paraplegia|Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9|not provided|Hereditary spastic paraplegia 30

★★☆☆2025→ Residue 69

NM_001244008.2(KIF1A):c.1048C>T (p.Arg350Trp)Likely pathogenic

Hereditary spastic paraplegia 30|Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30|not provided

★★☆☆2025→ Residue 350

NM_001244008.2(KIF1A):c.2840del (p.Leu947fs)Pathogenic

Neuropathy, hereditary sensory, type 2C|Neuropathy, hereditary sensory and autonomic, type 2A|Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9|KIF1A-related disorder|not provided

★★☆☆2025→ Residue 947

NM_001244008.2(KIF1A):c.296C>T (p.Thr99Met)Pathogenic

Intellectual disability, autosomal dominant 9|PEHO syndrome|not provided|Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory, type 2C|KIF1A-related disorder

★★☆☆2025→ Residue 99

NM_001244008.2(KIF1A):c.500G>A (p.Arg167His)Pathogenic

Hereditary spastic paraplegia 30|Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9|not provided

★★☆☆2025→ Residue 167

NM_001244008.2(KIF1A):c.506G>A (p.Arg169Lys)Pathogenic

not provided

★★☆☆2025→ Residue 169

NM_001244008.2(KIF1A):c.760C>T (p.Arg254Trp)Pathogenic

not provided|Inborn genetic diseases|Neuropathy, hereditary sensory and autonomic, type 2A;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30|Intellectual disability, autosomal dominant 9|Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30|KIF1A-related disorder

★★☆☆2025→ Residue 254

NM_001244008.2(KIF1A):c.38G>A (p.Arg13His)Pathogenic

Spastic paraplegia|not provided|Neuropathy, hereditary sensory, type 2C;Hereditary spastic paraplegia 30;Intellectual disability, autosomal dominant 9|Intellectual disability, autosomal dominant 9|Hereditary spastic paraplegia 30

★★☆☆2025→ Residue 13

NM_001244008.2(KIF1A):c.798+1G>APathogenic

not provided|Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9

★★☆☆2025

NM_001244008.2(KIF1A):c.773C>T (p.Thr258Met)Pathogenic

Hereditary spastic paraplegia 30;Intellectual disability, autosomal dominant 9;Neuropathy, hereditary sensory, type 2C|Inborn genetic diseases|Hereditary spastic paraplegia 30|not provided|Intellectual disability, autosomal dominant 9|Neuropathy, hereditary sensory, type 2C|Hereditary spastic paraplegia

★★☆☆2024→ Residue 258

Tissue Expression6 tissues

Brain

100%

Heart

Ovary

Liver

Bone Marrow

Lung

Gene Interaction Network6 neighbors

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Structure17 PDB hits

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PDB4EJQ · 1.89 Å · X-ray

View on RCSB

ConstraintgnomAD v4.1

LOEUFⓘ

0.30Highly Constrained

pLIⓘ

1.00Intolerant

Observed/Expected LoF0.24 [0.18–0.30]

Rankings3 dim

Where KIF1A stands among ~20K protein-coding genes

#3,998of 20,598
Most Researched118 · top quartile
#332of 5,509
Most Pathogenic Variants204 · top 10%
#1,185of 17,882
Most Constrained (LOEUF)0.30 · top 10%