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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NMI
N-myc and STAT interactor
Chromosome 2 · 2q23.3
NCBI Gene: 9111Ensembl: ENSG00000123609.12HGNC: HGNC:7854UniProt: Q13287
85PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of non-canonical NF-kappaB signal transductioncytoplasmnucleusGO:0005615type 2 diabetes mellitussevere acute respiratory syndromefrozen shoulderpneumoconiosis
✦AI Summary

NMI (N-myc and STAT interactor) is a pleiotropic immune regulator with dual intracellular and extracellular functions. Intracellularly, NMI enhances STAT1 and STAT5-dependent transcription by recruiting CBP/p300 coactivators in response to IL-2 and IFN-γ 1. NMI forms complexes with IFI35 to suppress antiviral responses by promoting IRF7 degradation via TRIM21-mediated ubiquitination 2, while simultaneously inhibiting NF-κB signaling to prevent endothelial dysfunction 3. Extracellularly, macrophage-secreted NMI functions as a damage-associated molecular pattern (DAMP), activating TLR4-NF-κB signaling in adjacent macrophages to promote pro-inflammatory cytokine release during sepsis and tissue injury 4. In cancer biology, NMI acts as a tumor suppressor in lung adenocarcinoma by suppressing PI3K/AKT and COX-2/PGE2 pathways while inhibiting NF-κB acetylation; low NMI expression correlates with poor prognosis 5. NMI also participates in a BRCA1-containing tricomplex that inhibits c-Myc-induced telomerase activation 6. These multifaceted roles position NMI as both a critical immunoregulator and potential therapeutic target for inflammatory and malignant diseases.

Sources cited
1
NMI enhances STAT1 and STAT5-dependent transcription by recruiting CBP/p300 coactivators in response to IL-2 and IFN-γ
PMID: 9989503
2
NMI facilitates IRF7 degradation via TRIM21-mediated ubiquitination to suppress type I interferon production during IAV infection
PMID: 33761305
3
NMI-IFI35 complex inhibits NF-κB signaling by blocking p65 nuclear translocation and endothelial cell proliferation
PMID: 29350881
4
Extracellular NMI functions as a DAMP, activating TLR4-NF-κB signaling in macrophages during sepsis and tissue injury, with elevated serum NMI correlating with severe inflammation mortality
PMID: 29038465
5
NMI acts as a tumor suppressor in lung adenocarcinoma by suppressing PI3K/AKT, MMP2/MMP9, and COX-2/PGE2 pathways; low NMI expression predicts poor prognosis
PMID: 29025423
6
NMI forms a tricomplex with BRCA1 and c-Myc that inhibits hTERT promoter activity; BRCA1 mutations disrupt this inhibition
PMID: 11916966
Disease Associationsⓘ20
type 2 diabetes mellitusOpen Targets
0.41Moderate
severe acute respiratory syndromeOpen Targets
0.37Weak
frozen shoulderOpen Targets
0.32Weak
pneumoconiosisOpen Targets
0.25Weak
smoking initiationOpen Targets
0.13Weak
neoplasmOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.07Suggestive
Failure to thriveOpen Targets
0.06Suggestive
gliomaOpen Targets
0.06Suggestive
hepatocellular carcinomaOpen Targets
0.05Suggestive
attention deficit hyperactivity disorderOpen Targets
0.05Suggestive
substance abuseOpen Targets
0.05Suggestive
ovarian neoplasmOpen Targets
0.05Suggestive
mathematical abilityOpen Targets
0.05Suggestive
diabetes mellitusOpen Targets
0.04Suggestive
pseudohyperaldosteronism type 2Open Targets
0.03Suggestive
brain cancerOpen Targets
0.03Suggestive
gastric mucosal hypertrophyOpen Targets
0.03Suggestive
lung cancerOpen Targets
0.03Suggestive
endometriosisOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MYCNProtein interaction99%MYCProtein interaction92%STAT2Protein interaction91%SOX10Protein interaction88%KAT5Protein interaction87%STAT1Protein interaction86%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
47%
Lung
45%
Ovary
28%
Heart
15%
Brain
11%
Gene Interaction Network
Click a node to explore
NMIMYCNMYCSTAT2SOX10KAT5STAT1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q13287
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.46LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.94 [0.62–1.46]
RankingsWhere NMI stands among ~20K protein-coding genes
  • #5,623of 20,598
    Most Researched85
  • #14,931of 17,882
    Most Constrained (LOEUF)1.46
Genes detectedNMI
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Mobile health (m-health) smartphone interventions for adolescents and adults with overweight or obesity.
PMID: 38375882
Cochrane Database Syst Rev · 2024
1.00
2
Challenging the pipeline.
PMID: 34525380
Stem Cell Reports · 2021
0.90
3
Downregulation of NMI promotes tumor growth and predicts poor prognosis in human lung adenocarcinomas.
PMID: 29025423
Mol Cancer · 2017
0.80
4
NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury.
PMID: 29038465
Nat Commun · 2017
0.70
5
A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer.
PMID: 11916966
J Biol Chem · 2002
0.60