Disease relevance of KIF1B

• KIF1B knockout mice die at birth from apnea due to nervous system defects [1].
• The KIF1B heterozygotes have a defect in transporting synaptic vesicle precursors and suffer from progressive muscle weakness similar to human neuropathies [1].
• To date, a genetic defect in one of these genes has been identified in over 1,000 unrelated patients manifesting a wide range of phenotypes, i.e., Charcot-Marie-Tooth disease type 1 (CMT1) and type 2 (CMT2), Dejerine-Sottas syndrome (DSS), hereditary neuropathy with liability to pressure palsies (HNPP), and congenital hypomyelination (CH) [2].
• Recently, a missense mutation in the gene for the kinesin superfamily KIF1B was reported as the cause of Charcot Marie Tooth disease type 2A (CMT2A) [3].
• Mutational study of the 1p located genes p18ink4c, Patched-2, RIZ1 and KIF1B in oligodendrogliomas [4].

Psychiatry related information on KIF1B

• Together with the clinical data, MRCP is a very important technique in the diagnostic and therapeutic decision making of KLP [5].
• Mean thermal pain thresholds were significantly increased in the feet of the CMT2 patients when compared with the controls and they were significantly higher in the hands of the CMT2 than in the CMT1 patients [6].

High impact information on KIF1B

• Charcot-Marie-Tooth disease type 2A was previously mapped to an interval containing KIF1B [1].
• The kinesin superfamily motor protein KIF1B has been shown to transport mitochondria [1].
• KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria [7].
• In situ hybridization revealed that KIF1B is expressed abundantly in differentiated nerve cells [7].
• To further elucidate the mechanism of organelle transport, we cloned a novel member of the mouse kinesin superfamily, KIF1B [7].

Chemical compound and disease context of KIF1B

• Finally, a tri-peptide motif, KLP, which showed homology with laminin 5 (a ligand for alpha3beta1 integrin), was identified as a binding peptide for peritoneal tumors of gastric cancer [8].

Biological context of KIF1B

• Genomic structure and mutational analysis of the human KIF1B gene which is homozygously deleted in neuroblastoma at chromosome 1p36.2 [9].
• The KIF1Balpha and KIF1Bbeta are alternative splicing products of the KIF1B gene located on 1p36 [10].
• Affected members had the typical CMT2 phenotype [11].
• We examined 11 unrelated CMT2 families for linkage to CMT2A using short tandem repeat (STR) polymorphisms [12].
• We identified a novel neurofilament-light missense mutation (C64T) that causes the disease in a large Slovenian CMT2 family [13].

Anatomical context of KIF1B

• In COS-7 cells, KIF1B colocalized with lysosomal markers and expression of a mutant form of KIF1Bbeta, lacking the motor domain, impaired the intracellular distribution of lysosomes [14].
• We sought to quantify axonal loss in two upper extremity muscles in CMT1A and CMT2 subjects using the electrophysiologic endpoint measure of motor unit number estimation (MUNE) [15].
• Northern blot analysis demonstrated that KIAA0591 mRNA was preferentially expressed in both adult and fetal brains, kidney, skeletal muscle and pancreas [16].
• Here we identified a complete open reading frame of the KIAA0591 gene by screening a cDNA library derived from human substantia nigra [16].
• KIAA0591 was expressed in favorable NBLs at higher levels than in unfavorable NBLs, although RT-PCR SSCP analysis showed no mutation within the coding region of the KIAA0591 gene, when 8 neuroblastoma tissues and 15 neuroblastoma-derived cell lines were examined [16].

Associations of KIF1B with chemical compounds

• Thus, the triad of inconstant metabolite concentrations, inconstant KLP/KBA, and delta F both inconstant and non-zero, indicates that there is no state of equilibrium for these metabolite couplets in human plasma [17].

Physical interactions of KIF1B

• CHP binds to regions adjacent to the motor domains of KIF1Bbeta2 and KIF1B, but not to those of the other KIF1 family members, KIF1A and KIF1C [18].

Other interactions of KIF1B

• The region between the DFF45 and KIF1B genes was defined as homozygous deletion by Southern blotting [19].
• BACKGROUND: Axonal neuropathy linked to the CMT2A locus was originally associated with a mutation in the KIF1B gene [20].
• Twenty unrelated CMT2 patients, as well as 26 others with an undetermined form of CMT, also were screened for mutations in NF-L, but no additional mutations were found [11].
• One patient with a CMT2 clinical phenotype had three myelin protein zero mutations (I89N+V92M+I162M) [21].
• Eleven Cx32 mutations were found in 12 families, six with a CMT2 diagnosis, three with a CMT1 diagnosis and three with unclassified CMT [22].

Analytical, diagnostic and therapeutic context of KIF1B

• Despite clinical findings of normal or near-normal strength and small reductions in compound muscle action potential (CMAP) amplitude, MUNE values were significantly lower in CMT2 subjects in proximal muscles, consistent with more diffuse denervation [15].
• The KLP-containing fraction was identified with the KLP radioimmunoassay [23].
• Clinical findings are very important data to be considered in the differential diagnosis of KLP [5].
• Phage clones displaying the sequence KLP showed 64-fold higher binding to peritoneal tumors than control phage and were preferentially distributed in tumors rather than in normal organs after intraperitoneal injection into mice [8].

References