NIPBL Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the NIPBL gene, its role in cohesin loading, associated disorders, and expression patterns.
Gene Information Card
| Symbol | NIPBL |
|---|---|
| Full Name | NIPBL, cohesin loading factor |
| Gene Type | Protein coding |
| Chromosomal Location | 5p13.2 |
| NCBI Gene ID | 25836 ncbi.nlm.nih.gov/gene/25836 |
| Ensembl ID | ENSG00000164190 |
| UniProt ID | Q6KC79 |
| OMIM ID | 608667 |
| HGNC ID | 13362 |
| Aliases | IDN3, CDLS1, Scc2, hScc2 |
Description
The NIPBL gene encodes a protein that functions as a key component of the cohesin loading complex. It is essential for sister chromatid cohesion, DNA repair, and gene regulation. Mutations in NIPBL are the primary cause of Cornelia de Lange syndrome (CdLS), a multisystem developmental disorder. The protein interacts with the cohesin complex to load it onto chromatin, facilitating proper chromosome segregation and transcriptional control.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cornelia de Lange syndrome (CdLS) | Haploinsufficiency due to loss-of-function mutations reduces NIPBL protein levels, impairing cohesin loading and gene expression regulation. | ClinVar, OMIM |
| Brachmann-de Lange syndrome | Same as CdLS; historically used interchangeably. | OMIM |
| Intellectual disability (non-syndromic) | Rare missense variants may affect NIPBL function without full CdLS phenotype. | ClinVar |
| Cancer (various) | Somatic mutations and altered expression have been reported, but role is not fully established. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Heart | 8.5 | Medium |
| Liver | 7.1 | Low |
| Kidney | 9.3 | Medium |
| Testis | 12.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 11.5 | Cervical cancer cell line; high expression |
| K562 | 9.8 | Leukemia cell line; moderate expression |
| MCF7 | 8.2 | Breast cancer cell line; moderate expression |
| HepG2 | 7.6 | Liver cancer cell line; low-moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.7423C>T (p.Arg2475Ter) | Nonsense | ~5% of CdLS cases | Premature stop codon leading to truncated protein and haploinsufficiency |
| c.6046A>G (p.Thr2016Ala) | Missense | Rare | Alters protein function; associated with mild CdLS phenotype |
| c.1A>G (p.Met1Val) | Start codon loss | Rare | Loss of translation initiation, leading to reduced protein levels |
| c.7330_7331del (p.Leu2444ValfsTer3) | Frameshift | ~2% of CdLS cases | Frameshift causing premature termination and loss of function |
Mutation functional classification
Loss of Function (LOF)
Most NIPBL mutations are loss-of-function, leading to haploinsufficiency. This is the primary mechanism in CdLS.
Gain of Function (GOF)
No clear gain-of-function mutations have been identified; NIPBL acts as a dosage-sensitive gene.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with cohesin loading, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • protein binding |
| • chromatin binding | • cohesin loading |
| • sister chromatid cohesion | • DNA repair |
| • transcription regulation |
Pathways
• Cohesin loading pathway
• Cell cycle - sister chromatid cohesion
• DNA damage response
• Developmental gene regulation
Protein Summary
The NIPBL protein (also known as Scc2) is a large, 2804-amino-acid protein that serves as a loader for the cohesin complex. It binds to chromatin and facilitates the loading of cohesin rings onto DNA, which is essential for sister chromatid cohesion during mitosis and meiosis. NIPBL also plays roles in DNA double-strand break repair and transcriptional regulation by influencing chromatin architecture. The protein contains HEAT repeats that mediate protein-protein interactions. Mutations leading to reduced NIPBL function cause Cornelia de Lange syndrome, characterized by facial dysmorphism, growth retardation, and limb anomalies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NIPBL Knockout HEK293 Cell Line | EDJ-KQ51139 | Human | 25836 | Details Get a Quote |
| NIPBL Knockout HeLa Cell Line | EDJ-KQ55828 | Human | 25836 | Details Get a Quote |
| NIPBL Knockout A-549 Cell Line | EDJ-KQ64320 | Human | 25836 | Details Get a Quote |
| NIPBL Knockout HCT 116 Cell Line | EDJ-KQ72773 | Human | 25836 | Details Get a Quote |
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