NFIA Gene - Nuclear Factor I A
Transcriptional regulator involved in brain development, urinary tract formation, and myeloid differentiation
Gene Information Card
| Symbol | NFIA |
|---|---|
| Full Name | Nuclear Factor I A |
| Gene Type | protein-coding |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | 4774 ncbi.nlm.nih.gov/gene/4774 |
| Ensembl ID | ENSG00000162599 |
| UniProt ID | Q12857 |
| OMIM ID | 600727 |
| HGNC ID | 7784 |
| Aliases | NFI-A, NFI-L, CTF, NF1-A |
Description
NFIA encodes a member of the nuclear factor I (NFI) family of transcription factors. These proteins bind to DNA as homodimers or heterodimers and regulate the expression of a variety of genes. NFIA is critical for brain development, particularly in the formation of the corpus callosum and hippocampus, and also plays roles in urinary tract development and myeloid cell differentiation. Mutations in NFIA are associated with brain malformations, urinary tract defects, and acute myeloid leukemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Brain malformation (corpus callosum agenesis/hypoplasia, ventriculomegaly) | Loss of function due to heterozygous deletion or mutation reduces NFIA dosage, impairing glial and neuronal differentiation during forebrain development. | ClinVar, OMIM #600727 |
| Urinary tract defects (hydronephrosis, vesicoureteral reflux) | NFIA haploinsufficiency disrupts ureteric bud branching and nephron formation. | ClinVar, OMIM #600727 |
| Acute myeloid leukemia (AML) | Somatic mutations (e.g., frameshift, nonsense) lead to loss of NFIA function, blocking myeloid differentiation and promoting leukemogenesis. | COSMIC, PubMed |
| Macrocephaly / megalencephaly | NFIA deletion or mutation associated with increased brain size, possibly due to altered glial cell proliferation. | ClinVar, OMIM #600727 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Kidney | 8.3 | Medium |
| Lung | 6.1 | Medium |
| Liver | 4.2 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | High expression |
| K562 (leukemia) | 7.5 | Medium expression |
| HepG2 | 5.1 | Low expression |
| SH-SY5Y (neuroblastoma) | 9.8 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.886C>T (p.Gln296*) | Nonsense | <0.1% | Loss of function – premature stop, likely nonsense-mediated decay |
| c.1120_1121del (p.Leu374fs) | Frameshift | <0.1% | Loss of function – truncated protein |
| Whole gene deletion | Copy number loss | <0.1% | Haploinsufficiency – associated with brain and urinary tract anomalies |
| c.457G>A (p.Gly153Arg) | Missense | <0.1% | Likely loss of function – disrupts DNA-binding domain |
Mutation functional classification
Loss of Function (LOF)
Most NFIA mutations (nonsense, frameshift, deletions, missense in DNA-binding domain) result in loss of function, leading to haploinsufficiency or complete loss of transcriptional activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NFIA.
Dominant Negative (DN)
Dominant-negative effects are not well documented; most pathogenic variants act through haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity (GO:0003700) | • RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978) |
| • Chromatin binding (GO:0003682) | • Regulation of transcription by RNA polymerase II (GO:0006357) |
| • Nervous system development (GO:0007399) | • Kidney development (GO:0001822) |
| • Myeloid cell differentiation (GO:0030099) |
Pathways
• NFI transcription factor network
• Transcriptional regulation of granulopoiesis
• Development of the corpus callosum
Protein Summary
NFIA is a 509-amino acid transcription factor containing an N-terminal DNA-binding domain and a C-terminal transactivation domain. It forms homo- or heterodimers with other NFI family members and binds to palindromic DNA sequences (TTGGCNNNNNGCCAA). The protein is involved in chromatin remodeling and regulates genes essential for glial cell differentiation, kidney morphogenesis, and myeloid lineage commitment. Post-translational modifications include phosphorylation and acetylation, which modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NFIA Knockout HEK293 Cell Line | EDJ-KQ3887 | Human | 4774 | Details Get a Quote |
| NFIA Knockout A-549 Cell Line | EDJ-KQ26105 | Human | 4774 | Details Get a Quote |
| NFIA Knockout HeLa Cell Line | EDJ-KQ26106 | Human | 4774 | Details Get a Quote |
| NFIA Knockout HCT 116 Cell Line | EDJ-KQ24753 | Human | 4774 | Details Get a Quote |
| NFIA Knockout THLE-2 Cell Line | EDC07744 | Human | 4774 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
