KIF5B

Chr 10

kinesin family member 5B

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

NCBI Gene: 3799ENSG00000170759UniProt: P33176OMIM: 602809

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]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.28
Clinical Summary— KIF5B
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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.
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ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 99 VUS of 142 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
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?
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?
LoF OE?0.17 (0.10–0.28)
0≤0.351.4
Missense OE?0.61 (0.56–0.68)
0≤0.61.4
Synonymous OE?1.04
0≤1.21.6
LoF obs/exp: 10 / 59.4Missense obs/exp: 306 / 497.9Syn Z: -0.38
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateKIF5B-related diseaseOTHERAD

This gene — mechanism propensity

DN
0.6646th %ile
GOF
0.5465th %ile
LOF
0.61top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.28
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

142 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic4
VUS99
Likely Benign8
Benign5
Conflicting2
1
Pathogenic
4
Likely Pathogenic
99
VUS
8
Likely Benign
5
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
0
0
1
Likely Pathogenic
0
4
0
0
4
VUS
6
91
2
0
99
Likely Benign
0
4
3
1
8
Benign
0
0
3
2
5
Conflicting
—2
Total610083119

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap KIF5B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

KIF5B · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients