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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KIF1A
kinesin family member 1A
Chromosome 2 · 2q37.3
NCBI Gene: 547Ensembl: ENSG00000130294.18HGNC: HGNC:888UniProt: A0A3B3IT28
118PubMed Papers
24Diseases
0Drugs
204Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-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 23. 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
1
KIF1A transports synaptic vesicle and active zone proteins via recognition of PI(3,5)P2 and active ARL8
PMID: 37824668
2
KIF1A (SPG30) mediates axon transport; HSP involves motor-sensory axon degeneration in long CNS axons
PMID: 23897027
3
KIF1A mutations identified in >1% of hereditary spastic paraplegia cases in large diagnostic cohort
PMID: 34983064
4
KIF1A C-terminal variants associated with ALS; enhance binding of synaptic vesicle precursors
PMID: 36284339
5
KIF1A-associated neurological disorder (KAND) is ultrarare neurodegenerative disease responsive to antisense oligonucleotide therapy
PMID: 39122967
6
KIF1A promotes neuroendocrine prostate cancer differentiation via OGT-mediated O-GlcNAcylation
PMID: 39505875
Disease Associationsⓘ24
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
not provided|Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30|Intellectual disability, autosomal dominant 9|Hereditary spastic paraplegia 30
★★☆☆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
Intellectual disability, autosomal dominant 9|PEHO syndrome|Hereditary spastic paraplegia 30|not provided|Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30|Syndromic intellectual disability|Inborn genetic diseases|Spastic paraplegia 30A, autosomal dominant
★★☆☆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|Hereditary spastic paraplegia 30|Inborn genetic diseases
★★☆☆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|Hereditary spastic paraplegia 30|Inborn genetic diseases|not provided
★★☆☆2025→ Residue 11
NM_001244008.2(KIF1A):c.757G>A (p.Glu253Lys)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|KIF1A-related disorder
★★☆☆2025→ Residue 253
NM_001244008.2(KIF1A):c.2350C>T (p.Arg784Ter)Pathogenic
Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9|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|Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30|not provided
★★☆☆2025→ Residue 167
NM_001244008.2(KIF1A):c.760C>T (p.Arg254Trp)Pathogenic
not provided|Inborn genetic diseases|Intellectual disability, autosomal dominant 9|Neuropathy, hereditary sensory and autonomic, type 2A;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30|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.506G>A (p.Arg169Lys)Pathogenic
not provided
★★☆☆2025→ Residue 169
NM_001244008.2(KIF1A):c.38G>A (p.Arg13His)Pathogenic
Spastic paraplegia|not provided|Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30|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
View on ClinVar ↗
Related Genes
KIF5CProtein interaction100%KIF5BProtein interaction100%TUBA1AProtein interaction100%PAFAH1B1Protein interaction99%KLC1Protein interaction99%SYPProtein interaction99%
Tissue Expression6 tissues
Brain
100%
Heart
2%
Ovary
0%
Liver
0%
Bone Marrow
0%
Lung
0%
Gene Interaction Network
Click a node to explore
KIF1AKIF5CKIF5BTUBA1APAFAH1B1KLC1SYP
PROTEIN STRUCTURE
Preparing viewer…
PDB4EJQ · 1.89 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.30Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.24 [0.18–0.30]
RankingsWhere KIF1A stands among ~20K protein-coding genes
  • #3,998of 20,598
    Most Researched118 · top quartile
  • #329of 5,498
    Most Pathogenic Variants204 · top 10%
  • #1,185of 17,882
    Most Constrained (LOEUF)0.30 · top 10%
Genes detectedKIF1A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Clinical and genetic spectra of 1550 index patients with hereditary spastic paraplegia.
PMID: 34983064
Brain · 2022
1.00
2
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis · 2022
0.90
3
Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms.
PMID: 23897027
Acta Neuropathol · 2013
0.80
4
Phosphatidylinositol 3,5-bisphosphate facilitates axonal vesicle transport and presynapse assembly.
PMID: 37824668
Science · 2023
0.70
5
Antisense oligonucleotide therapy in an individual with KIF1A-associated neurological disorder.
PMID: 39122967
Nat Med · 2024
0.60