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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NFIB
nuclear factor I B
Chromosome 9 Β· 9p23-p22.3
NCBI Gene: 4781Ensembl: ENSG00000147862.18HGNC: HGNC:7785UniProt: A0A0A0MRX8
128PubMed Papers
21Diseases
0Drugs
35Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
RNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription factor activity, RNA polymerase II-specificDNA-binding transcription activator activity, RNA polymerase II-specificDNA bindingmacrocephaly, acquired, with impaired intellectual developmentmacrocephaly-developmental delay syndromeIntellectual disabilityMacrocephaly
✦AI Summary

NFIB is a transcription factor with critical roles in neuronal development and cell fate specification. As a DNA-binding transcription factor, NFIB recognizes palindromic sequences in promoter regions and directly regulates gene transcription 1. In the developing retina, NFIB is selectively expressed in late progenitor cells where it controls bipolar interneuron and MΓΌller glia specification while promoting proliferative quiescence 1. NFIB is also essential for astrocyte differentiation from pluripotent stem cells, as its overexpression with SOX9 rapidly generates functional astrocytes resembling adult cells 2. Beyond development, NFIB functions as an oncogenic transcription factor in several cancers. In adenoid cystic carcinomas, NFIB participates in the pathogenic MYB-NFIB fusion translocation 3. In small cell lung cancer, NFIB is a direct target of ASCL1 and contributes to malignant behavior 4. In castration-resistant prostate cancer, NFIB upregulation drives epithelial-to-mesenchymal transition and metastasis by directly regulating EMT factors CDH1 and VIM 5. These findings establish NFIB as a multifunctional regulator spanning developmental processes and pathological conditions.

Sources cited
1
NFIB is selectively expressed in late retinal progenitor cells and controls bipolar interneuron and MΓΌller glia cell fate specification while promoting proliferative quiescence
PMID: 31128945
2
NFIB overexpression with SOX9 rapidly and efficiently induces functional astrocytes from human pluripotent stem cells
PMID: 30127505
3
NFIB participates in the t(6;9) MYB-NFIB translocation characteristic of adenoid cystic carcinomas
PMID: 20452298
4
NFIB is a direct target of ASCL1 transcription factor in small cell lung cancer and contributes to malignant behavior
PMID: 27452466
5
NFIB upregulation in AR-negative castration-resistant prostate cancer drives epithelial-to-mesenchymal transition and metastasis by directly regulating EMT factors CDH1 and VIM
PMID: 38536119
Disease Associationsβ“˜21
macrocephaly, acquired, with impaired intellectual developmentOpen Targets
0.72Strong
macrocephaly-developmental delay syndromeOpen Targets
0.63Moderate
Intellectual disabilityOpen Targets
0.53Moderate
MacrocephalyOpen Targets
0.53Moderate
Abnormality of the skeletal systemOpen Targets
0.52Moderate
genetic disorderOpen Targets
0.45Moderate
coronary artery diseaseOpen Targets
0.45Moderate
mathematical abilityOpen Targets
0.42Moderate
neurodegenerative diseaseOpen Targets
0.40Weak
open-angle glaucomaOpen Targets
0.38Weak
type 2 diabetes mellitusOpen Targets
0.38Weak
glaucomaOpen Targets
0.38Weak
lipomaOpen Targets
0.37Weak
breast ductal adenocarcinomaOpen Targets
0.37Weak
minor salivary gland adenoid cystic carcinomaOpen Targets
0.37Weak
Salivary Gland Carcinoma ex Pleomorphic AdenomaOpen Targets
0.37Weak
salivary gland mucoepidermoid carcinomaOpen Targets
0.37Weak
Salivary Gland Pleomorphic AdenomaOpen Targets
0.37Weak
syndromic complex neurodevelopmental disorderOpen Targets
0.37Weak
schizophreniaOpen Targets
0.36Weak
Macrocephaly, acquired, with impaired intellectual developmentUniProt
Pathogenic Variants35
NM_001190737.2(NFIB):c.115C>T (p.Arg39Cys)Pathogenic
not provided|Macrocephaly, acquired, with impaired intellectual development
β˜…β˜…β˜†β˜†2026β†’ Residue 39
NM_001190737.2(NFIB):c.265C>T (p.Arg89Ter)Pathogenic
Macrocephaly;Intellectual disability|Macrocephaly, acquired, with impaired intellectual development|Macrocephaly|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 89
NM_001190737.2(NFIB):c.901C>T (p.Arg301Ter)Pathogenic
Macrocephaly, acquired, with impaired intellectual development|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 301
NM_001190737.2(NFIB):c.367C>T (p.Gln123Ter)Likely pathogenic
not provided|Macrocephaly, acquired, with impaired intellectual development
β˜…β˜…β˜†β˜†2024β†’ Residue 123
NM_001190737.2(NFIB):c.109C>T (p.Arg37Ter)Pathogenic
Intellectual disability;Macrocephaly|Macrocephaly, acquired, with impaired intellectual development|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 37
NM_001190737.2(NFIB):c.376A>G (p.Lys126Glu)Pathogenic
Macrocephaly;Intellectual disability|Macrocephaly, acquired, with impaired intellectual development|Marfanoid habitus and intellectual disability|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 126
NM_001190737.2(NFIB):c.142C>T (p.Arg48Ter)Pathogenic
Macrocephaly, acquired, with impaired intellectual development|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 48
NM_001190737.2(NFIB):c.373_376del (p.Asp125fs)Pathogenic
Macrocephaly, acquired, with impaired intellectual development|Inborn genetic diseases
β˜…β˜…β˜†β˜†2021β†’ Residue 125
NM_001190737.2(NFIB):c.395T>C (p.Leu132Pro)Pathogenic
Macrocephaly;Intellectual disability|Macrocephaly, acquired, with impaired intellectual development
β˜…β˜…β˜†β˜†2019β†’ Residue 132
NM_001190737.2(NFIB):c.844G>T (p.Glu282Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 282
NM_001190737.2(NFIB):c.1331G>A (p.Arg444Gln)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 444
NM_001190737.2(NFIB):c.816del (p.Thr274fs)Pathogenic
Macrocephaly, acquired, with impaired intellectual development
β˜…β˜†β˜†β˜†2024β†’ Residue 274
NM_001190737.2(NFIB):c.377_378del (p.Lys126fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 126
NM_001190737.2(NFIB):c.1465C>T (p.Gln489Ter)Likely pathogenic
Macrocephaly, acquired, with impaired intellectual development
β˜…β˜†β˜†β˜†2024β†’ Residue 489
NM_001190737.2(NFIB):c.1067C>G (p.Ser356Ter)Likely pathogenic
Macrocephaly, acquired, with impaired intellectual development
β˜…β˜†β˜†β˜†2024β†’ Residue 356
NM_001190737.2(NFIB):c.1061-1G>CLikely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2024
NM_001190737.2(NFIB):c.330C>A (p.Asp110Glu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 110
NM_001190737.2(NFIB):c.26dup (p.Gln10fs)Pathogenic
Macrocephaly, acquired, with impaired intellectual development
β˜…β˜†β˜†β˜†2023β†’ Residue 10
NM_001190737.2(NFIB):c.364C>T (p.Arg122Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 122
NM_001190737.2(NFIB):c.577G>T (p.Gly193Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 193
View on ClinVar β†—
Related Genes
NFIXProtein interaction83%NFICProtein interaction82%MPDZProtein interaction74%NFIAProtein interaction72%SLC1A3Protein interaction72%HMGA2Protein interaction71%
Tissue Expression6 tissues
Heart
100%
Brain
89%
Liver
46%
Ovary
40%
Lung
31%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
NFIBNFIXNFICMPDZNFIASLC1A3HMGA2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O00712
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.30Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.18 [0.11–0.30]
RankingsWhere NFIB stands among ~20K protein-coding genes
  • #3,659of 20,598
    Most Researched128 Β· top quartile
  • #1,672of 5,498
    Most Pathogenic Variants35
  • #1,141of 17,882
    Most Constrained (LOEUF)0.30 Β· top 10%
Genes detectedNFIB
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Histological types of breast cancer: how special are they?
PMID: 20452298
Mol Oncol Β· 2010
1.00
2
Mechanisms of small cell lung cancer metastasis.
PMID: 33296145
EMBO Mol Med Β· 2021
0.90
3
Single-Cell RNA-Seq Analysis of Retinal Development Identifies NFI Factors as Regulating Mitotic Exit and Late-Born Cell Specification.
PMID: 31128945
Neuron Β· 2019
0.80
4
ASCL1 and NEUROD1 Reveal Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct Genetic Programs.
PMID: 27452466
Cell Rep Β· 2016
0.70
5
Rapid and efficient induction of functional astrocytes from human pluripotent stem cells.
PMID: 30127505
Nat Methods Β· 2018
0.60