NFIB

Chr 9AD

nuclear factor I B

Also known as: CTF, HMGIC/NFIB, MACID, NF-I/B, NF1-B, NFI-B, NFI-RED, NFIB2

NCBI Gene: 4781ENSG00000147862UniProt: O00712OMIM: 600728

NFIB encodes a transcriptional activator essential for proper brain development that recognizes specific DNA sequences in viral and cellular promoters. Mutations cause autosomal dominant macrocephaly with impaired intellectual development. This gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.225), indicating that such variants are likely pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.231 OMIM phenotype
Clinical Summary— NFIB
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Gene-Disease Validity (ClinGen)
syndromic complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.999
Z-score 4.55
OE 0.07 (0.03–0.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.47Z-score
OE missense 0.57 (0.50–0.65)
151 obs / 264.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.07 (0.03–0.23)
0≤0.351.4
Missense OE0.57 (0.50–0.65)
0≤0.61.4
Synonymous OE1.18
0≤1.21.6
LoF obs/exp: 2 / 27.9Missense obs/exp: 151 / 264.2Syn Z: -1.38
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNFIB-related macrocephaly, acquired, with impaired intellectual developmentLOFAD
DN
0.4190th %ile
GOF
0.3391th %ile
LOF
0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.23

Literature Evidence

LOFNFIB haploinsufficiency is associated with intellectual disability and macrocephaly.PMID:30388402

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NFIB · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients