KIF1B

Chr 1ADSomatic

kinesin family member 1B

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/SomaticLOEUF 0.172 OMIM phenotypes
Clinical SummaryKIF1B
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Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease type 2A1 · ADNo Known Disease Relationship

No known disease relationship

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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 8.57
OE 0.10 (0.060.17)
Highly constrained

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

Missense Constraint
3.60Z-score
OE missense 0.68 (0.630.72)
663 obs / 980.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.10 (0.060.17)
00.351.4
Missense OE0.68 (0.630.72)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 11 / 106.5Missense obs/exp: 663 / 980.1Syn Z: 0.17
DN
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),PMID:18726616

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KIF1B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC