Topic
KIFAP3
About: KIFAP3 is a research topic. Over the lifetime, 6 publications have been published within this topic receiving 262 citations. The topic is also known as: FLA3 & KAP-1.
Papers
University of Nantes1, Duke University2, Oslo University Hospital3, University of Paris4, Nationwide Children's Hospital5, Necker-Enfants Malades Hospital6, Massachusetts Eye and Ear Infirmary7, University of California, Los Angeles8, Michigan State University9, University of Missouri10, Children's Memorial Hospital11, Northwestern University12
TL;DR: The genetic, cell-based, and in vivo modeling data delineate an autosomal-dominant syndromic retinal ciliopathy in humans and suggest that multiple KIF3B pathomechanisms can impair kinesin-driven ciliary transport in the photoreceptor.
Abstract: Kinesin-2 enables ciliary assembly and maintenance as an anterograde intraflagellar transport (IFT) motor. Molecular motor activity is driven by a heterotrimeric complex comprised of KIF3A and KIF3B or KIF3C plus one non-motor subunit, KIFAP3. Using exome sequencing, we identified heterozygous KIF3B variants in two unrelated families with hallmark ciliopathy phenotypes. In the first family, the proband presents with hepatic fibrosis, retinitis pigmentosa, and postaxial polydactyly; he harbors a de novo c.748G>C (p.Glu250Gln) variant affecting the kinesin motor domain encoded by KIF3B. The second family is a six-generation pedigree affected predominantly by retinitis pigmentosa. Affected individuals carry a heterozygous c.1568T>C (p.Leu523Pro) KIF3B variant segregating in an autosomal-dominant pattern. We observed a significant increase in primary cilia length in vitro in the context of either of the two mutations while variant KIF3B proteins retained stability indistinguishable from wild type. Furthermore, we tested the effects of KIF3B mutant mRNA expression in the developing zebrafish retina. In the presence of either missense variant, rhodopsin was sequestered to the photoreceptor rod inner segment layer with a concomitant increase in photoreceptor cilia length. Notably, impaired rhodopsin trafficking is also characteristic of recessive KIF3B models as exemplified by an early-onset, autosomal-recessive, progressive retinal degeneration in Bengal cats; we identified a c.1000G>A (p.Ala334Thr) KIF3B variant by genome-wide association study and whole-genome sequencing. Together, our genetic, cell-based, and in vivo modeling data delineate an autosomal-dominant syndromic retinal ciliopathy in humans and suggest that multiple KIF3B pathomechanisms can impair kinesin-driven ciliary transport in the photoreceptor.
42 citations
TL;DR: None of 140 SNPs genotyped within the KIFAP3 locus had an effect on survival (log-rank P value for rs1541160 = 0.47) or on gene expression in that region, illustrating the complexities associated with analyzing ALS phenotypes for association.
Abstract: It was recently reported that rs1541160 on chromosome 1q24.2 has a marked effect on survival of amyotrophic lateral sclerosis (ALS) patients by influencing KIFAP3 expression. The cohorts used in that study were collected from ALS specialty clinics. We attempted to replicate these findings in a population-based cohort of 504 Italian ALS patients. None of 140 SNPs genotyped within the KIFAP3 locus (including rs1541160) had an effect on survival (log-rank P value for rs1541160 = 0.47) or on gene expression in that region. These data illustrate the complexities associated with analyzing ALS phenotypes for association.
40 citations
TL;DR: The incidence of the UMN-ALS phenotype in the CC patients of this cohort supports the hypothesis that the SNP rs1541160 within the KIFAP3 gene is a potential modifier of the ALS phenotype.
Abstract: Background: Some authors have recently reported that the CC genotype of single-nucleotide polymorphism (SNP) rs1541160 mapping within the kinesin-associated protein 3 (KIFA
17 citations
TL;DR: The results suggest that these SNPs are unlikely to be a common cause of SALS in Chinese populations.
15 citations
TL;DR: Investigation of Kinesin Associated Protein 3 using breast cancer tissue microarrays revealed overexpression of KIFAP3 protein in 84% (240/285) of breast cancers indicating the utility of the integrated approach of combining computational analysis with experimental biology.
Abstract: Gene expression profiling studies on breast cancer have generated catalogs of differentially expressed genes. However, many of these genes have not been investigated for their expression at the protein level. It is possible to systematically evaluate such genes in a high-throughput fashion for their overexpression at the protein level using breast cancer tissue microarrays. Our strategy involved integration of information from publicly available repositories of gene expression to prepare a list of genes upregulated at the mRNA level in breast cancer followed by curation of the published literature to identify those genes that were not tested for overexpression at the protein level. We identified Kinesin Associated Protein 3 (KIFAP3) as one such molecule for further validation at the protein level. Immunohistochemical labeling of KIFAP3 using breast cancer tissue microarrays revealed overexpression of KIFAP3 protein in 84% (240/285) of breast cancers indicating the utility of our integrated approach of combining computational analysis with experimental biology.
6 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2020 | 1 |
| 2012 | 2 |
| 2011 | 1 |
| 2010 | 1 |
| 2009 | 1 |