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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NIT1
nitrilase 1
Chromosome 1 · 1q23.3
NCBI Gene: 4817Ensembl: ENSG00000158793.15HGNC: HGNC:7828UniProt: B7Z410
34PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleusmitochondriondeaminated glutathione amidase activitycytoplasmneurodegenerative diseaseAlzheimer diseasemultiple sclerosislysosomal storage disease
✦AI Summary

NIT1 (nitrilase 1) is a metabolite repair enzyme that catalyzes hydrolysis of deaminated glutathione (dGSH), a harmful byproduct generated by transaminases during primary metabolism 1. This repair function prevents accumulation of non-functional dGSH and is physiologically significant, with NIT1 deficiency linked to neurological disorders 2. Beyond its enzymatic role, NIT1 functions as a tumor suppressor through multiple mechanisms. It directly interacts with the tumor suppressor FHIT, forming a tetrameric complex 3, and suppresses colorectal cancer proliferation by activating TGFβ1-Smad2/3 signaling pathways 4. NIT1 loss of expression promotes cell growth and resistance to DNA damage stress while increasing NMBA-induced tumor incidence. In cancer cells, NIT1 enhances apoptotic responsiveness additively with FHIT's tumor suppressor activity 5. NIT1 also acts as a negative regulator of primary T cells. The protein localizes to the mitochondrion, nucleus, and cytoplasm, reflecting its dual roles in metabolic repair and tumor suppression. These findings suggest NIT1 represents a convergence point between fundamental metabolic homeostasis and cancer prevention.

Sources cited
1
NIT1 functions as a metabolite repair enzyme that hydrolyzes deaminated glutathione (dGSH)
PMID: 28373563
2
NIT1 deficiency in humans is linked to neurological disorder (brain small vessel disease)
PMID: 41390003
3
NIT1 physically interacts with FHIT tumor suppressor protein and forms tetrameric structures
PMID: 36766695
4
NIT1 suppresses colorectal cancer cell proliferation through TGFβ1-Smad2/3 signaling pathway activation
PMID: 29449642
5
NIT1 collaborates with FHIT in tumor suppression and has tumor suppressor properties in lung cancer
PMID: 21189170
Disease Associationsⓘ21
neurodegenerative diseaseOpen Targets
0.49Moderate
Alzheimer diseaseOpen Targets
0.22Weak
lysosomal storage diseaseOpen Targets
0.22Weak
multiple sclerosisOpen Targets
0.22Weak
Parkinson diseaseOpen Targets
0.22Weak
headache disorderOpen Targets
0.09Suggestive
lung cancerOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
cancerOpen Targets
0.06Suggestive
non-small cell lung carcinomaOpen Targets
0.04Suggestive
Abnormality of the skeletal systemOpen Targets
0.03Suggestive
Crohn's diseaseOpen Targets
0.03Suggestive
ankylosing spondylitisOpen Targets
0.02Suggestive
psoriasisOpen Targets
0.02Suggestive
sclerosing cholangitisOpen Targets
0.02Suggestive
ulcerative colitisOpen Targets
0.02Suggestive
adenocarcinomaOpen Targets
0.02Suggestive
squamous cell carcinomaOpen Targets
0.02Suggestive
Neoplasm of the lungOpen Targets
0.02Suggestive
Brain small vessel disease 4UniProt
Pathogenic Variants2
NM_005600.3(NIT1):c.591+2T>GLikely pathogenic
Susceptibility to severe COVID-19
★☆☆☆2024
NM_005600.3(NIT1):c.198_199del (p.Cys67_Ala68insTer)Pathogenic
Brain small vessel disease 4
☆☆☆☆2025→ Residue 67
View on ClinVar ↗
Related Genes
GSTM5Shared pathway100%GSTT2Shared pathway100%GSTT2BShared pathway100%GSTT4Shared pathway100%ETHE1Shared pathway100%FHITProtein interaction90%
Tissue Expression6 tissues
Liver
100%
Lung
41%
Ovary
39%
Heart
38%
Brain
19%
Bone Marrow
13%
Gene Interaction Network
Click a node to explore
NIT1GSTM5GSTT2GSTT2BGSTT4ETHE1FHIT
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q86X76
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.04LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.77 [0.57–1.04]
RankingsWhere NIT1 stands among ~20K protein-coding genes
  • #11,196of 20,598
    Most Researched34
  • #4,493of 5,498
    Most Pathogenic Variants2
  • #10,416of 17,882
    Most Constrained (LOEUF)1.04
Genes detectedNIT1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Chronic postsurgical pain: A European survey.
PMID: 38414426
Eur J Anaesthesiol · 2024
1.00
2
NIT2 dampens BRD1 phase separation and restrains oxidative phosphorylation to enhance chemosensitivity in gastric cancer.
PMID: 39565874
Sci Transl Med · 2024
0.90
3
[Construction and identification of procaryotic expression vector of human NIT1 gene].
PMID: 21189170
Zhongguo Fei Ai Za Zhi · 2005
0.80
4
The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit.
PMID: 36766695
Cells · 2023
0.70
5
NIT1 suppresses tumour proliferation by activating the TGFβ1-Smad2/3 signalling pathway in colorectal cancer.
PMID: 29449642
Cell Death Dis · 2018
0.60