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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NIT2
nitrilase family member 2
Chromosome 3 · 3q12.2
NCBI Gene: 56954Ensembl: ENSG00000114021.13HGNC: HGNC:29878UniProt: Q9NQR4
37PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
omega-amidase activityextracellular exosomecytosoloxaloacetate metabolic processsynovium disorderlung adenocarcinomaneoplasmpoisoning
✦AI Summary

NIT2 (nitrilase family member 2) is a cytosolic omega-amidase enzyme with dual functions in metabolism and tumor suppression. Primary metabolic function: NIT2 catalyzes hydrolysis of α-ketoglutaramate and α-ketosuccinamate to produce α-ketoglutarate and oxaloacetate, respectively, thereby linking sulfur metabolism to the tricarboxylic acid cycle 1. The enzyme contains a catalytic triad (E43, K112, C153) essential for substrate binding and catalytic activity 1. Mechanism: NIT2 activity is redox-sensitive, with reversible oxidation of cysteine residues impairing catalytic function under oxidative stress 2. Beyond metabolism, NIT2 exhibits tumor-suppressive properties through non-metabolic mechanisms: it inhibits cell growth via G2 arrest by upregulating 14-3-3sigma 3 and restrains oxidative phosphorylation by inhibiting BRD1-mediated histone acetylation 4. Disease relevance: NIT2 expression inversely correlates with chemoresistance in gastric cancer, where depletion promotes 5-FU resistance 4. Paradoxically, NIT2 overexpression predicts poor prognosis in tongue squamous cell carcinoma 5, and genetic variants increasing NIT2 expression elevate lung adenocarcinoma risk 6. Clinical significance: NIT2 loss impairs endothelial angiogenesis and induces senescence 2, suggesting therapeutic potential in cancer chemosensitization and vascular dysfunction.

Sources cited
1
NIT2 is an ω-amidase that hydrolyzes α-ketoglutaramate and α-ketosuccinamate; contains catalytic triad essential for activity
PMID: 22674578
2
NIT2 activity is redox-sensitive with reversible cysteine oxidation; regulates endothelial glutamine metabolism and angiogenesis
PMID: 41408486
3
NIT2 ectopic expression inhibits cell growth via G2 arrest by upregulating 14-3-3sigma; shows allelic imbalance in cancers
PMID: 17488281
4
NIT2 depletion causes 5-FU chemoresistance in gastric cancer; NIT2 restrains OXPHOS through BRD1 inhibition
PMID: 39565874
5
NIT2 overexpression in tongue squamous cell carcinoma correlates with decreased disease-free survival and poor prognosis
PMID: 31925645
6
rs277646-T allele in NIT2 increases lung adenocarcinoma risk through alternative polyadenylation affecting miR-650 binding
PMID: 39003419
Disease Associationsⓘ20
synovium disorderOpen Targets
0.28Weak
lung adenocarcinomaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
poisoningOpen Targets
0.03Suggestive
glaucomaOpen Targets
0.03Suggestive
open-angle glaucomaOpen Targets
0.02Suggestive
atrial fibrillationOpen Targets
0.02Suggestive
colorectal cancerOpen Targets
0.01Suggestive
ulcerative colitisOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
gastric cancerOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
colorectal carcinomaOpen Targets
0.01Suggestive
systemic juvenile idiopathic arthritisOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
Down syndromeOpen Targets
0.01Suggestive
tongue squamous cell carcinomaOpen Targets
0.01Suggestive
chromophobe renal cell carcinomaOpen Targets
0.01Suggestive
lung cancerOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CSProtein interaction96%GOT1Protein interaction92%GOT2Protein interaction92%GOT1L1Protein interaction83%IDH1Protein interaction83%IDH2Protein interaction83%
Tissue Expression6 tissues
Liver
100%
Heart
25%
Bone Marrow
24%
Ovary
21%
Lung
20%
Brain
15%
Gene Interaction Network
Click a node to explore
NIT2CSGOT1GOT2GOT1L1IDH1IDH2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9NQR4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.25LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.87 [0.62–1.25]
RankingsWhere NIT2 stands among ~20K protein-coding genes
  • #10,658of 20,598
    Most Researched37
  • #13,176of 17,882
    Most Constrained (LOEUF)1.25
Genes detectedNIT2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NIT2 dampens BRD1 phase separation and restrains oxidative phosphorylation to enhance chemosensitivity in gastric cancer.
PMID: 39565874
Sci Transl Med · 2024
1.00
2
Growth inhibitory effect of the human NIT2 gene and its allelic imbalance in cancers.
PMID: 17488281
FEBS J · 2007
0.90
3
Integrating apaQTL and eQTL analysis identifies a potential causal variant associated with lung adenocarcinoma risk in the Chinese population.
PMID: 39003419
Commun Biol · 2024
0.80
4
Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomes Attenuates Experimental Periodontitis in Mice Partly by Delivering miRNAs.
PMID: 40078652
Int J Nanomedicine · 2025
0.70
5
NIT2 overexpression predicts poor prognosis in tongue squamous cell carcinoma patients.
PMID: 31925645
Mol Biol Rep · 2020
0.60