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GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KIF5B
kinesin family member 5B
Chromosome 10 · 10p11.22
NCBI Gene: 3799Ensembl: ENSG00000170759.12HGNC: HGNC:6324UniProt: P33176
267PubMed Papers
20Diseases
2Drugs
4Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of membrane potentialpositive regulation of potassium ion transportvesicle transport along microtubuleprotein bindingnon-small cell lung carcinomacancermedullary thyroid gland carcinomaneoplasm
✦AI Summary

KIF5B is a microtubule-dependent motor protein with diverse cellular functions. Its primary role involves anterograde axonal and dendritic transport, particularly of mitochondria and lysosomes 12. KIF5B mechanistically functions as a kinesin motor that interacts with adaptor proteins including TRAK1, OPTN, and EndoA2 to facilitate cargo movement along microtubules toward the plus end 23. Additionally, KIF5B regulates DNA damage response by generating DSB-capturing nuclear envelope tubules that enhance DNA repair through microtubule-dependent repositioning mechanisms 4. During immune responses, KIF5B drives polarization of cytolytic granules and microtubule-organizing centers toward immune synapses in NK cells [UniProt annotation]. Disease relevance is substantial: KIF5B fusions with RET and ALK occur in non-small cell lung cancer (~2.5-73% of cases) and ALK-positive histiocytosis respectively, with KIF5B-ALK fusions showing robust responses to ALK inhibition 56. Clinically, KIF5B mutations and dysregulation are implicated in neurodegeneration when associated with impaired mitochondrial transport in amyotrophic lateral sclerosis and normal tension glaucoma contexts 2. Furthermore, KIF5B participates in mechanosensory signal transmission through Piezo2 trafficking in sensory neurons, suggesting therapeutic relevance for pain management 3.

Sources cited
1
KIF5B-RET is the most common RET fusion in non-small cell lung cancer (NSCLC), occurring in 1-3% of patients, providing a therapeutic target
PMID: 31715421
2
KIF5B-ALK fusions are recurrent in ALK-positive histiocytosis (detected in 27/37 cases), with robust responses to ALK inhibition in 11/11 treated patients
PMID: 34727172
3
KIF5B functions with other kinesins and the LINC complex to generate DSB-capturing nuclear envelope tubules that promote DNA repair at nuclear periphery
PMID: 38632359
4
KIF5b is involved in astrocyte-mediated mitochondrial transfer to neurons through tunneling nanotubes, regulated by CD38-cADPR-Ca2+ signaling
PMID: 40598228
5
OPTN directly interacts with KIF5B/TRAK1 complex to stabilize anterograde axonal mitochondrial transport; loss causes neurodegeneration in ALS and normal tension glaucoma
PMID: 39979261
6
KIF5B functions as an adaptor in EndoA2-mediated Piezo2 trafficking for touch and mechanical pain sensation in dorsal root ganglion neurons
PMID: 38475827
Disease Associationsⓘ20
non-small cell lung carcinomaOpen Targets
0.67Moderate
cancerOpen Targets
0.57Moderate
medullary thyroid gland carcinomaOpen Targets
0.55Moderate
neoplasmOpen Targets
0.51Moderate
kyphomelic dysplasiaOpen Targets
0.49Moderate
Intellectual disabilityOpen Targets
0.47Moderate
thyroid cancerOpen Targets
0.46Moderate
papillary thyroid carcinomaOpen Targets
0.44Moderate
Severe muscular hypotoniaOpen Targets
0.43Moderate
neurodegenerative diseaseOpen Targets
0.41Moderate
colon carcinomaOpen Targets
0.41Moderate
Global developmental delayOpen Targets
0.41Moderate
SeizureOpen Targets
0.40Moderate
malignant colon neoplasmOpen Targets
0.39Weak
breast cancerOpen Targets
0.39Weak
lung adenocarcinomaOpen Targets
0.38Weak
thyroid neoplasmOpen Targets
0.37Weak
adenosquamous lung carcinomaOpen Targets
0.37Weak
large cell lung carcinomaOpen Targets
0.37Weak
undifferentiated pleomorphic sarcomaOpen Targets
0.37Weak
Pathogenic Variants4
NM_004521.3(KIF5B):c.833G>A (p.Arg278Gln)Likely pathogenic
not provided|Feeding difficulties in infancy;Hypotonia;Motor delay
★★☆☆2025→ Residue 278
NM_004521.3(KIF5B):c.762CAA[1] (p.Asn255del)Pathogenic
Hypertrophic cardiomyopathy|Primary dilated cardiomyopathy;Skeletal myopathy;Ophthalmoplegia;Multiple joint contractures
★★☆☆2023→ Residue 255
NM_004521.3(KIF5B):c.1493T>C (p.Leu498Pro)Pathogenic
Feeding difficulties;Intellectual disability;Severe muscular hypotonia;Fatigable weakness of swallowing muscles
★☆☆☆→ Residue 498
NM_004521.3(KIF5B):c.2252A>G (p.His751Arg)Likely pathogenic
Brain atrophy;Hypoplasia of the corpus callosum;Global developmental delay;Attention deficit hyperactivity disorder;Seizure
☆☆☆☆2016→ Residue 751
View on ClinVar ↗
Drug Targets2
PRALSETINIBApproved
Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET inhibitor
medullary thyroid gland carcinoma
SELPERCATINIBApproved
Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET inhibitor
medullary thyroid gland carcinoma
Related Genes
NEFLProtein interaction100%KIF1AProtein interaction100%NEFHProtein interaction99%RANBP2Protein interaction99%RETProtein interaction99%TPM3Protein interaction98%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
88%
Brain
65%
Lung
33%
Ovary
20%
Liver
16%
Gene Interaction Network
Click a node to explore
KIF5BNEFLKIF1ANEFHRANBP2RETTPM3
PROTEIN STRUCTURE
Preparing viewer…
PDB1BG2 · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.43Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.30 [0.21–0.43]
RankingsWhere KIF5B stands among ~20K protein-coding genes
  • #1,398of 20,598
    Most Researched267 · top 10%
  • #540of 1,025
    FDA-Approved Drug Targets2
  • #3,688of 5,498
    Most Pathogenic Variants4
  • #2,335of 17,882
    Most Constrained (LOEUF)0.43 · top quartile
Genes detectedKIF5B
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
RET fusions in solid tumors.
PMID: 31715421
Cancer Treat Rev · 2019
1.00
2
ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition.
PMID: 34727172
Blood · 2022
0.90
3
DNA double-strand break-capturing nuclear envelope tubules drive DNA repair.
PMID: 38632359
Nat Struct Mol Biol · 2024
0.80
4
Systems mapping of bidirectional endosomal transport through the crowded cell.
PMID: 39276769
Curr Biol · 2024
0.72
5
Mechanisms of electroacupuncture-induced neuroprotection in acute stroke rats: the role of astrocyte-mediated mitochondrial transfer.
PMID: 40598228
Cell Commun Signal · 2025
0.70