NIPBL

2583671175ENSG00000164190ENSMUSG00000022141Q6KC79Q6KCD5NM_015384NM_133433NM_027707NM_201232NP_056199NP_597677NP_081983NP_957684Nipped-B-like protein (Nipbl), also known as Scc2 or delangin is a protein that in humans is encoded by the NIPBL gene. Nipbl is required for the association of cohesin with DNA and is the major subunit of the cohesin loading complex. Heterozygous mutations in NIPBL account for an estimated 60% of case of Cornelia de Lange Syndrome. Nipped-B-like protein (Nipbl), also known as Scc2 or delangin is a protein that in humans is encoded by the NIPBL gene. Nipbl is required for the association of cohesin with DNA and is the major subunit of the cohesin loading complex. Heterozygous mutations in NIPBL account for an estimated 60% of case of Cornelia de Lange Syndrome. Nipbl is a large hook-shaped protein containing HEAT repeats. Nipbl forms a complex with Mau4 known as the cohesin loading complex or Kollerin. Cohesin is a ring-shaped protein complex responsible for sister chromatid cohesion. Cohesin is also thought to mediate enhancer-promoter interactions and generate Topologically associating domain. As well as mediating cohesion and regulating DNA architecture the cohesin complex is required for DNA repair by homologous recombination. Given that Nipbl is required for cohesin's association with DNA it is thought that Nipbl is also required for all of these processes. Consistently, inactivation of Nipbl results in the loss topologically associating domains and cohesion. Nipbl/Scc2 binds dynamically to chromatin principally through an association with cohesin. Nipbl’s movement within chromatin is consistent with a mechanism involving hopping between chromosomal cohesin rings. A cohesin-independent function in the regulation of gene expression has also been demonstrated for Nipbl. Mutations in this gene result in Cornelia de Lange syndrome (CdLS), a disorder characterized by dysmorphic facial features, growth delay, limb reduction defects, and mental retardation. As these mutations are usually heterozygous, CdLS is caused by a reduction in the abundance of Nipbl not a complete loss. Experiments on cells from patients and mice indicate that the reduction is by less than half. It is not known why a reduction in Nipbl expression results in CdLS. This article incorporates text from the United States National Library of Medicine, which is in the public domain.