NFIB Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the NFIB transcription factor gene, its expression, associated diseases, and mutations.
Gene Information Card
| Symbol | NFIB |
|---|---|
| Full Name | Nuclear Factor I B |
| Gene Type | Protein coding |
| Chromosomal Location | 9p23-p22.3 |
| NCBI Gene ID | 4781 ncbi.nlm.nih.gov/gene/4781 |
| Ensembl ID | ENSG00000147862 |
| UniProt ID | O00712 |
| OMIM ID | 600728 |
| HGNC ID | 7785 |
| Aliases | NFI-B, NF1B, HMGIC/NFIB fusion, CTF (CCAAT-box-binding transcription factor) |
Description
The NFIB gene encodes nuclear factor I B, a member of the NFI family of transcription factors. NFIB binds to specific DNA sequences (TTGGCNNNNNGCCAA) and regulates transcription of various genes involved in development, differentiation, and cellular proliferation. It plays critical roles in brain, lung, and muscle development. NFIB is also implicated in several cancers, where it can act as a tumor suppressor or oncogene depending on context. Alternative splicing generates multiple isoforms with distinct functions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lung cancer (small cell lung cancer, SCLC) | NFIB amplification and overexpression promote tumor progression and metastasis; NFIB cooperates with ASCL1 and other oncogenes. | COSMIC, PubMed |
| Breast cancer | NFIB expression is associated with poor prognosis; promotes epithelial-to-mesenchymal transition (EMT) and metastasis. | COSMIC, PubMed |
| Neuroblastoma | NFIB is a tumor suppressor; loss of NFIB expression correlates with aggressive disease and MYCN amplification. | COSMIC, PubMed |
| Colorectal cancer | NFIB overexpression enhances cell proliferation and invasion; associated with poor survival. | COSMIC, PubMed |
| Intellectual disability (autosomal dominant) | Heterozygous mutations in NFIB cause intellectual disability with speech delay and dysmorphic features. | ClinVar, OMIM |
| Macrocephaly and developmental delay | NFIB mutations lead to abnormal brain development; macrocephaly and corpus callosum abnormalities. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Muscle (skeletal) | 6.1 | Low |
| Heart | 5.4 | Low |
| Kidney | 4.2 | Low |
| Liver | 2.1 | Not detected |
| Testis | 1.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 15.2 | High expression |
| MCF7 (breast cancer) | 8.7 | Medium expression |
| HepG2 (liver cancer) | 3.4 | Low expression |
| K562 (leukemia) | 2.9 | Low expression |
| SH-SY5Y (neuroblastoma) | 1.5 | Very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1000C>T (p.Arg334Ter) | Nonsense | Rare (0.01%) | Loss of function; causes intellectual disability |
| c.1204A>G (p.Thr402Ala) | Missense | 0.05% | Unknown; possibly benign |
| Gene amplification | Copy number gain | Frequent in SCLC (30-40%) | Oncogenic; promotes tumor growth |
| c.1507_1508insA (p.Thr503AsnfsTer5) | Frameshift | Rare | Loss of function; associated with developmental delay |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (nonsense, frameshift) lead to haploinsufficiency, causing neurodevelopmental disorders. In cancer, loss of NFIB can promote tumor progression in some contexts (e.g., neuroblastoma).
Gain of Function (GOF)
Gain-of-function via gene amplification or overexpression is oncogenic in lung and breast cancers, enhancing metastatic potential.
Dominant Negative (DN)
Dominant-negative effects have been proposed for certain missense mutations that disrupt DNA binding or dimerization, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Transcriptional regulation by NFIB
• p53 pathway (NFIB regulates p53 target genes)
• Wnt signaling pathway (NFIB modulates beta-catenin activity)
• TGF-beta signaling pathway (NFIB interacts with SMADs)
• Cell cycle regulation (NFIB controls cyclin expression)
Protein Summary
NFIB is a 481-amino acid protein with a conserved N-terminal DNA-binding domain and a C-terminal transactivation domain. It forms homo- or heterodimers with other NFI family members (NFIA, NFIC, NFIX) to regulate gene expression. NFIB is involved in chromatin remodeling and interacts with histone-modifying enzymes. Its expression is developmentally regulated, with high levels in neural and lung tissues. Post-translational modifications include phosphorylation and sumoylation, affecting its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NFIB Knockout HEK293 Cell Line | EDJ-KQ5335 | Human | 4781 | Details Get a Quote |
| NFIB Knockout A-549 Cell Line | EDJ-KQ28421 | Human | 4781 | Details Get a Quote |
| NFIB Knockout HCT 116 Cell Line | EDJ-KQ28422 | Human | 4781 | Details Get a Quote |
| NFIB Knockout HeLa Cell Line | EDC10174 | Human | 4781 | Details Get a Quote |
