| Full Name | Nipped-B Like |
|---|---|
| Symbol | NIPBL |
| Chromosomal Location | 5p13.2 |
| NCBI Gene ID | [25836](https://www.ncbi.nlm.nih.gov/gene/25836) |
| OMIM | [608667](https://omim.org/entry/608667) |
| Ensembl ID | [ENSG00000104249](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000104249) |
| UniProt | [Q6KF10](https://www.uniprot.org/uniprot/Q6KF10) |
| Associated Diseases | [Cornelia de Lange Syndrome](/cornelia-de-lange-syndrome), [Intellectual Disability](/intellectual-disability), [Developmental Disorders](/developmental-disorders) |
NIPBL (Nipped-B Like) is the primary cohesin loading factor, essential for the deposition of the cohesin complex onto chromatin. Named after the Drosophila Nipped-B gene, NIPBL mutations cause the majority of Cornelia de Lange syndrome (CdLS) cases, a multisystem developmental disorder with significant neurological manifestations[1]. Beyond cohesin loading, NIPBL regulates gene expression programs critical for neurodevelopment and brain function.
NIPBL, together with its partner MAU2, forms the cohesin loader complex that:
This loading is ATP-dependent and requires the SMC1A-SMC3 ATPase head domains.
NIPBL mediates cohesin-dependent gene regulation through:
In neural development, NIPBL-regulated genes include:
NIPBL facilitates cohesin recruitment to DNA breaks for homologous recombination repair and checkpoint signaling[5].
NIPBL mutations account for approximately 60% of CdLS cases, presenting with:
Mutation types:
CdLS patients with NIPBL mutations exhibit:
NIPBL functions as a tumor suppressor in certain contexts:
NIPBL is ubiquitously expressed with elevated levels in:
Post-mitotic neurons maintain NIPBL expression for ongoing cohesin-mediated chromatin organization.
Moderate expression throughout adult brain with enrichment in:
CdLS management is supportive, addressing:
Research directions include:
Krantz ID, et al. Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B. Nature Genetics. 2004. ↩︎
Higashi TL, et al. A structure-based mechanism for cohesin loading onto chromosomes. Nature. 2020. ↩︎
Kagey MH, et al. Mediator and cohesin connect gene expression and chromatin architecture. Nature. 2010. ↩︎
Dorsett D, Strom L. The ancient and evolving roles of cohesin in gene expression and DNA repair. Current Biology. 2012. ↩︎
Watrin E, Peters JM. The cohesin complex is required for the DNA damage-induced G2/M checkpoint. Molecular Cell. 2006. ↩︎
Tonkin ET, et al. NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome. Nature Genetics. 2004. ↩︎
Oliver C, et al. Cornelia de Lange syndrome: extending the physical and psychological phenotype. American Journal of Medical Genetics Part A. 2008. ↩︎
Kon A, et al. Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. Nature Genetics. 2013. ↩︎
Merckenschlager M, Odom DT. CTCF and cohesin: linking gene regulatory elements with disease genes. Cell. 2013. ↩︎
Kline AD, et al. Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement. Nature Reviews Genetics. 2018. ↩︎