KIF5B

Chr 10

kinesin family member 5B

Also known as: HEL-S-61, KINH, KNS, KNS1, UKHC

NCBI Gene: 3799ENSG00000170759UniProt: P33176

Enables identical protein binding activity; microtubule binding activity; and microtubule motor activity. Involved in several processes, including natural killer cell mediated cytotoxicity; positive regulation of protein localization to plasma membrane; and vesicle transport along microtubule. Located in several cellular components, including centriolar satellite; cytosol; and nuclear membrane. [provided by Alliance of Genome Resources, Jul 2025]

123
ClinVar variants
16
Pathogenic / LP
0.99
pLI score· haploinsufficient
2
Active trials
Clinical Summary— KIF5B
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 98 VUS of 123 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.994
Z-score 5.94
OE 0.17 (0.10–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.06Z-score
OE missense 0.61 (0.56–0.68)
306 obs / 497.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.10–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.56–0.68)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 10 / 59.4Missense obs/exp: 306 / 497.9Syn Z: -0.38

ClinVar Variant Classifications

123 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic4
VUS98
Likely Benign4
Benign3
Conflicting2
12
Pathogenic
4
Likely Pathogenic
98
VUS
4
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
11
0
12
Likely Pathogenic
0
2
2
0
4
VUS
4
88
6
0
98
Likely Benign
0
4
0
0
4
Benign
0
0
2
1
3
Conflicting
—2
Total495211123

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KIF5B · protein map & ClinVar variants

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

Gene2Phenotype Curations

KIF5B-related disease

moderate
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RET fusions in solid tumors.
Li AY et al.·Cancer Treat Rev
2019Review
ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition.
Kemps PG et al.·Blood
2022
Cabozantinib for the treatment of non-small cell lung cancer with KIF5B-RET fusion. An example of swift repositioning.
Song M et al.·Arch Pharm Res
2015Review
Dominantly acting KIF5B variants with pleiotropic cellular consequences cause variable clinical phenotypes.
Flex E et al.·Hum Mol Genet
2023
Clinical, Morphologic, and Genomic Findings in Spitz Tumors With RET Fusion: A Series of 31 Cases.
Donati M et al.·Mod Pathol
2025Cohort
Role of cytoplasmic dynein and kinesins in adenovirus transport.
Scherer J et al.·FEBS Lett
2020Review
Dominant negative variants in KIF5B cause osteogenesis imperfecta via down regulation of mTOR signaling.
Marom R et al.·PLoS Genet
2023
Personalized Medicine in Histiocytic Disorders: Novel Targets in Patients Without MAPK Alterations.
Smith KER et al.·JCO Precis Oncol
2024Case report
Oncogenic Function of a KIF5B-MET Fusion Variant in Non-Small Cell Lung Cancer.
Gow CH et al.·Neoplasia
2018
ALK-positive histiocytosis in 12 Asian children.
Feng X et al.·Hum Pathol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
KIF5B-driven unfolded protein response reprograms breast cancer immunosuppressive microenvironment for single-cell guided therapeutic targeting.
Liu Y et al.·Discov Oncol
2026🔓 Open Access
Glucose-stimulated KIF5B-driven microtubule sliding organizes microtubule networks in mouse pancreatic β cells.
Bracey KM et al.·Elife
2025🔓 Open AccessFunctional
Identification of immunogenic KIF5B-RET fusion neopeptides driving immune stimulation in tumor specific CD8+ T cells.
Castillo MB et al.·Front Immunol
2025🔓 Open Access
Human OPN-derived peptide SV prevents BPD model through interacting with KIF5B to repair mitochondrial damage and inhibit apoptosis.
Yan R et al.·iScience
2025🔓 Open AccessFunctional
An unusual spindle cell variant of papillary thyroid carcinoma with KIF5B::MET fusion: report of a case.
Ding Q et al.·Virchows Arch
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Non-Small Cell Lung Cancer

Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity

RECRUITING
NCT01639508Phase PHASE2Memorial Sloan Kettering Cancer CenterStarted 2012-07
Cabozantinib
Solid TumorAdvanced Solid TumorMetastatic Cancer

KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II

RECRUITING
NCT05525858Seoul National University Bundang HospitalStarted 2022-09-28
AlectinibAtezolizumabErlotinib

External Resources

Links to major genomics databases and tools