KIF1B

Chr 1ADSomatic

kinesin family member 1B

Also known as: CMT2, CMT2A, CMT2A1, HMSNII, KLP, NBLST1

NCBI Gene: 23095 ENSG00000054523 UniProt: O60333 OMIM: 605995

This gene encodes a plus-end-directed microtubule motor protein that transports vesicles and organelles, including mitochondria, along microtubules. Mutations cause Charcot-Marie-Tooth disease type 2A1, a peripheral neuropathy, and increase susceptibility to neuroblastoma through autosomal dominant inheritance. The gene is extremely intolerant to loss-of-function variants (pLI ~1.0, LOEUF 0.17), indicating that complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables plus-end-directed microtubule motor activity. Involved in apoptotic process involved in development and mitochondrion transport along microtubule. Is active in mitochondrion. Implicated in Charcot-Marie-Tooth disease type 2A1; hepatocellular carcinoma; multiple sclerosis; neuroblastoma; and ovary epithelial cancer. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismAD/SomaticLOEUF 0.172 OMIM phenotypes

Clinical Summary— KIF1B

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Gene-Disease Validity (ClinGen)

Charcot-Marie-Tooth disease type 2A1 · ADLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 8.57

OE 0.10 (0.06–0.17)

Highly constrained

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

Missense Constraint?

3.60Z-score

OE missense 0.68 (0.63–0.72)

663 obs / 980.1 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.10 (0.06–0.17)

0≤0.351.4

Missense OE?0.68 (0.63–0.72)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 11 / 106.5Missense obs/exp: 663 / 980.1Syn Z: 0.17

This gene — mechanism propensity

0.5378th %ile

GOF

0.5759th %ile

LOF

0.64top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.17

Literature Evidence

LOFThe proband developed a leiomyosarcoma, and her father, who also carried the S1481N mutation, developed adenocarcinoma of the lung (211980). Analysis of tumor tissue revealed that all 4 neural crest tumors and the leiomyosarcoma retained both KIF1B alleles and showed no loss of heterozygosity (LOH),1

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

References