NIT2

gene
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Summary

NIT2 (nitrilase family member 2, HGNC:29878) is a protein-coding gene on chromosome 3q12.2, encoding Omega-amidase NIT2 (Q9NQR4). Has omega-amidase activity.

Enables omega-amidase activity. Involved in asparagine metabolic process; glutamine metabolic process; and oxaloacetate metabolic process. Located in centrosome and cytosol.

Source: NCBI Gene 56954 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 51 total
  • Druggable target: yes
  • MANE Select transcript: NM_020202

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:29878
Approved symbolNIT2
Namenitrilase family member 2
Location3q12.2
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000114021
Ensembl biotypeprotein_coding
OMIM616769
Entrez56954

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000394140, ENST00000460317, ENST00000465368, ENST00000472392, ENST00000478856, ENST00000480073, ENST00000497785, ENST00000867929, ENST00000867930, ENST00000867931, ENST00000867932

RefSeq mRNA: 1 — MANE Select: NM_020202 NM_020202

CCDS: CCDS33806

Canonical transcript exons

ENST00000394140 — 10 exons

ExonStartEnd
ENSE00001227514100355177100361635
ENSE00001517603100334757100334798
ENSE00003571494100348803100348881
ENSE00003574715100352404100352502
ENSE00003575356100341073100341161
ENSE00003592881100354772100354827
ENSE00003633258100339087100339205
ENSE00003656199100346181100346255
ENSE00003670178100339815100339935
ENSE00003680812100345585100345678

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 97.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.4818 / max 151.3254, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
3760532.34141811
376061.1404721

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
right lobe of liverUBERON:000111497.98gold quality
liverUBERON:000210796.91gold quality
mucosa of stomachUBERON:000119996.90gold quality
adult mammalian kidneyUBERON:000008296.41gold quality
nephron tubuleUBERON:000123196.26gold quality
kidneyUBERON:000211394.88gold quality
skin of abdomenUBERON:000141694.61gold quality
gastrocnemiusUBERON:000138894.57gold quality
skin of legUBERON:000151194.56gold quality
adrenal tissueUBERON:001830394.52gold quality
cortex of kidneyUBERON:000122594.34gold quality
muscle of legUBERON:000138394.32gold quality
kidney epitheliumUBERON:000481994.31gold quality
metanephros cortexUBERON:001053394.22gold quality
tibial nerveUBERON:000132394.15gold quality
gingival epitheliumUBERON:000194994.10gold quality
zone of skinUBERON:000001494.08gold quality
apex of heartUBERON:000209893.92gold quality
subcutaneous adipose tissueUBERON:000219093.90gold quality
islet of LangerhansUBERON:000000693.76gold quality
hindlimb stylopod muscleUBERON:000425293.50gold quality
gingivaUBERON:000182893.44gold quality
right adrenal glandUBERON:000123393.35gold quality
esophagus mucosaUBERON:000246993.34gold quality
omental fat padUBERON:001041493.31gold quality
right adrenal gland cortexUBERON:003582793.31gold quality
peritoneumUBERON:000235893.28gold quality
adipose tissueUBERON:000101393.26gold quality
adipose tissue of abdominal regionUBERON:000780893.25gold quality
left lobe of thyroid glandUBERON:000112093.23gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

ExperimentMarker?Max mean expression
E-HCAD-10yes32.62
E-ANND-3yes12.27
E-CURD-112yes9.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting NIT2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4476100.0068.182030
HSA-MIR-6876-5P100.0067.682126
HSA-MIR-186-5P99.9970.833707
HSA-MIR-471999.7372.103329
HSA-MIR-891B99.5969.811083
HSA-MIR-766-3P99.4765.241811
HSA-MIR-361299.4566.021333
HSA-MIR-65099.4565.771309
HSA-MIR-120699.3069.321016
HSA-MIR-642A-3P99.2367.671258
HSA-MIR-642B-3P99.2367.671258
HSA-MIR-3925-5P99.2167.901466
HSA-MIR-470599.1069.101091
HSA-MIR-589-5P98.7266.96927
HSA-MIR-4733-3P98.3565.20994
HSA-MIR-444398.0266.251928
HSA-MIR-15B-3P97.8566.68974
HSA-MIR-3162-5P95.6767.53794
HSA-MIR-6800-5P94.5964.80525
HSA-MIR-135A-3P94.1966.09495

Literature-anchored findings (GeneRIF, showing 6)

  • Genotype analysis in 4 types of tumor tissue showed allelic imbalance surrounding NIT2 locus; results show that NIT2 plays an important role in cell growth inhibition & links to malignancies, suggesting Nit2 may be a potential tumor suppressor candidate (PMID:17488281)
  • The activity and substrate specificity of human Nit2 was determined with alpha-ketoglutaramate and succinamate as substrates. (PMID:22674578)
  • Human NIT1/2 are not involved in the metabolism of vildagliptin. (PMID:25008847)
  • Downregulation of NIT2 inhibits colon cancer cell proliferation and induces cell cycle arrest through the caspase-3 and PARP pathways (PMID:25738796)
  • NIT2 overexpression predicts poor prognosis in tongue squamous cell carcinoma patients. (PMID:31925645)
  • A novel efficient producer of human omega-amidase (Nit2) in Escherichia coli. (PMID:34391728)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_rerionit2ENSDARG00000017590
mus_musculusNit2ENSMUSG00000022751
rattus_norvegicusNit2ENSRNOG00000027797
drosophila_melanogasterCG8132FBGN0037687

Paralogs (2): UPB1 (ENSG00000100024), NIT1 (ENSG00000158793)

Protein

Protein identifiers

Omega-amidase NIT2Q9NQR4 (reviewed: Q9NQR4)

Alternative names: Nitrilase homolog 2

All UniProt accessions (5): Q9NQR4, F8WF58, F8WF70, H7C579, V9HW91

UniProt curated annotations — full annotation on UniProt →

Function. Has omega-amidase activity. The role of omega-amidase is to remove potentially toxic intermediates by converting 2-oxoglutaramate and 2-oxosuccinamate to biologically useful 2-oxoglutarate and oxaloacetate, respectively.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in fetal brain (at protein level). Ubiquitous. Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, prostate, spleen, thymus, prostate, testis, ovary, small intestine and colon.

Similarity. Belongs to the carbon-nitrogen hydrolase superfamily. NIT1/NIT2 family.

RefSeq proteins (1): NP_064587* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR003010C-N_HydrolaseDomain
IPR036526C-N_Hydrolase_sfHomologous_superfamily
IPR045254Nit1/2_C-N_HydrolaseDomain

Pfam: PF00795

Enzyme classification (BRENDA):

  • EC 3.5.1.3 — omega-amidase (BRENDA: 20 organisms, 177 substrates, 34 inhibitors, 61 Km, 11 kcat entries)

Substrate kinetics (BRENDA)

23 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
2-OXOGLUTARAMATE0.0054–910
HYDROXYLAMINE1–1008
SUCCINAMATE0.14–176
GLUTARAMATE1.27–255
2-OXOSUCCINAMATE0.003–6.134
METHYL GLUTARATE1.8–523
METHYLAMINE30–553
ETHYL GLUTARATE9.9–312
ETHYL SUCCINATE8.3–172
METHYL SUCCINATE0.7–82
PROPYL GLUTARATE6.8–182
SUCCINATE30–632
2-HYDROXYSUCCINAMATE5.581
2-OXOGLUTARATE3.31
GAMMA-ETHYL 2-OXOGLUTARATE0.061

Catalyzed reactions (Rhea), 3 shown:

  • a monoamide of a dicarboxylate + H2O = a dicarboxylate + NH4(+) (RHEA:11716)
  • 2-oxoglutaramate + H2O = 2-oxoglutarate + NH4(+) (RHEA:32963)
  • 2-oxosuccinamate + H2O = oxaloacetate + NH4(+) (RHEA:59412)

UniProt features (15 total): modified residue 5, mutagenesis site 4, active site 3, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9NQR4-F197.620.98

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 43 (proton acceptor); 112 (proton donor); 153 (nucleophile)

Post-translational modifications (5): 26, 68, 68, 123, 130

Mutagenesis-validated functional residues (4):

PositionPhenotype
43loss of activity using succinamate as substrate.
112loss of activity using succinamate as substrate.
116–128less than 3% of wild-type activity using succinamate as substrate.
153loss of activity using succinamate as substrate.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-6798695Neutrophil degranulation

MSigDB gene sets: 130 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, GOBP_OXALOACETATE_METABOLIC_PROCESS, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_GLUTAMINE_METABOLIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, MULLIGHAN_NPM1_SIGNATURE_3_DN, MARTINEZ_RB1_AND_TP53_TARGETS_UP, GRADE_COLON_AND_RECTAL_CANCER_UP, MULLIGHAN_MLL_SIGNATURE_2_DN

GO Biological Process (3): oxaloacetate metabolic process (GO:0006107), obsolete asparagine metabolic process (GO:0006528), L-glutamine metabolic process (GO:0006541)

GO Molecular Function (4): omega-amidase activity (GO:0050152), 2-oxoglutaramate amidase activity (GO:0106008), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides (GO:0016811)

GO Cellular Component (8): extracellular region (GO:0005576), mitochondrion (GO:0005739), centrosome (GO:0005813), cytosol (GO:0005829), specific granule lumen (GO:0035580), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Innate Immune System1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
cytoplasm2
dicarboxylic acid metabolic process1
L-amino acid metabolic process1
proteinogenic amino acid metabolic process1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides1
omega-amidase activity1
catalytic activity1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds1
intracellular membrane-bounded organelle1
centriole1
microtubule organizing center1
secretory granule lumen1
specific granule1
extracellular vesicle1
intracellular organelle lumen1
tertiary granule1
intracellular anatomical structure1

Protein interactions and networks

STRING

1588 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
NIT2MDH2P40926490
NIT2ISOC2Q96AB3487
NIT2KYAT1Q16773484
NIT2CIAO3Q9H6Q4463
NIT2GLULP15104449
NIT2PKDCCQ504Y2428
NIT2ISOC1Q96CN7417
NIT2GPT2Q8TD30402
NIT2GLUD1P00367401
NIT2HARS1P12081400
NIT2GULP1Q9UBP9398
NIT2CDH8P55286387
NIT2DMGDHQ9UI17383
NIT2CINPQ9BW66381
NIT2NOC2LQ9Y3T9377

IntAct

12 interactions, top by confidence:

ABTypeScore
LYRM4NDUFAB1psi-mi:“MI:0914”(association)0.640
NIT2PDIA4psi-mi:“MI:0915”(physical association)0.400
CFTRNIT2psi-mi:“MI:0915”(physical association)0.370
CREB1NFIXpsi-mi:“MI:0914”(association)0.350
PRNPWDR91psi-mi:“MI:0914”(association)0.350
COQ6NDUFAB1psi-mi:“MI:0914”(association)0.350
repTMEM120Bpsi-mi:“MI:0914”(association)0.350
HLA-AAIPpsi-mi:“MI:0914”(association)0.350
AFG2BMMP24OSpsi-mi:“MI:0914”(association)0.350
NIT2psi-mi:“MI:0915”(physical association)0.000

BioGRID (89): LDHA (Co-fractionation), NIT2 (Co-fractionation), NIT2 (Co-fractionation), NIT2 (Co-fractionation), NIT2 (Co-fractionation), PARK7 (Co-fractionation), PRDX5 (Co-fractionation), PSMG4 (Co-fractionation), TPI1 (Co-fractionation), NIT2 (Affinity Capture-MS), NIT2 (Affinity Capture-MS), NIT2 (Affinity Capture-RNA), NIT2 (Co-fractionation), NIT2 (Co-fractionation), NIT2 (Co-fractionation)

ESM2 similar proteins: A0A140NCB4, A2R6M7, A2RA31, A4G3R1, B2JQY2, B6Q5I3, C6DKR8, G9AIU0, G9N4E3, O94660, P07874, P0DP64, P0DP66, P0DP68, P11444, P20960, P42593, P49954, P55175, P55176, P55178, P55357, P58054, P60327, P76008, Q0AJD9, Q216E0, Q221R3, Q2KXM7, Q3HVN1, Q44185, Q4VBV9, Q500U1, Q5S260, Q6INI7, Q6IR61, Q6N409, Q6RWG0, Q75SP7, Q82VS5

Diamond homologs: A0A140NCB4, A0A140NDS5, O31664, O76463, O76464, O94660, P0DP64, P0DP65, P0DP66, P0DP67, P55175, P55176, P55177, P55178, P58054, Q10166, Q28IE5, Q2T9R6, Q32LH4, Q47679, Q4VBV9, Q54JM9, Q557J5, Q5R4L6, Q6INI7, Q6IR61, Q75SP7, Q7TQ94, Q86X76, Q8RUF8, Q8VDK1, Q93NG1, Q94JV5, Q9JHW2, Q9NQR4, Q9UYV8, A6ZYQ3, B3LFZ1, B5VGI4, C4LYI2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

51 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance32
Likely benign1
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1644 predictions. Top by Δscore:

VariantEffectΔscore
3:100334794:GACCT:Gdonor_gain1.0000
3:100334796:CCT:Cdonor_gain1.0000
3:100334797:CT:Cdonor_gain1.0000
3:100334798:TGT:Tdonor_loss1.0000
3:100334799:G:GGdonor_gain1.0000
3:100339083:TCAGC:Tacceptor_loss1.0000
3:100339085:A:AGacceptor_gain1.0000
3:100339085:AGCTT:Aacceptor_loss1.0000
3:100339086:G:GGacceptor_gain1.0000
3:100339086:GC:Gacceptor_gain1.0000
3:100339086:GCT:Gacceptor_gain1.0000
3:100339086:GCTTT:Gacceptor_gain1.0000
3:100339202:GCCG:Gdonor_gain1.0000
3:100339203:CCGG:Cdonor_loss1.0000
3:100339206:G:Cdonor_loss1.0000
3:100339206:G:GGdonor_gain1.0000
3:100339210:G:GGdonor_gain1.0000
3:100339809:TTCTA:Tacceptor_loss1.0000
3:100339810:TCTA:Tacceptor_loss1.0000
3:100339811:CTAG:Cacceptor_loss1.0000
3:100339812:TA:Tacceptor_loss1.0000
3:100339813:A:Tacceptor_loss1.0000
3:100339814:GGAAT:Gacceptor_gain1.0000
3:100339899:G:GTdonor_gain1.0000
3:100339911:G:GTdonor_gain1.0000
3:100339912:A:Tdonor_gain1.0000
3:100341046:AT:Aacceptor_gain1.0000
3:100341047:T:TAacceptor_gain1.0000
3:100341065:A:AGacceptor_gain1.0000
3:100341067:T:TAacceptor_gain1.0000

AlphaMissense

1781 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
3:100341160:A:CK112T0.997
3:100341161:G:CK112N0.997
3:100341161:G:TK112N0.997
3:100346222:T:CF158L0.997
3:100346224:T:AF158L0.997
3:100346224:T:GF158L0.997
3:100348832:T:CF179L0.997
3:100348834:T:AF179L0.997
3:100348834:T:GF179L0.997
3:100352483:A:CS222R0.997
3:100352485:C:AS222R0.997
3:100352485:C:GS222R0.997
3:100346207:T:CC153R0.996
3:100348881:G:CR195P0.996
3:100345594:T:CF116L0.995
3:100345596:T:AF116L0.995
3:100345596:T:GF116L0.995
3:100346208:G:AC153Y0.995
3:100346209:C:GC153W0.995
3:100341159:A:CK112Q0.994
3:100341160:A:TK112M0.994
3:100346214:A:TD155V0.994
3:100352406:C:AA196D0.994
3:100345631:A:TE128V0.993
3:100348812:T:CL172P0.993
3:100352430:C:AA204D0.993
3:100341157:G:TR111I0.992
3:100345632:A:CE128D0.992
3:100345632:A:TE128D0.992
3:100346213:G:CD155H0.992

dbSNP variants (sampled 300 via entrez): RS1000006047 (3:100361312 T>C), RS1000144310 (3:100361708 A>G,T), RS1000244018 (3:100335156 C>G,T), RS1000504748 (3:100354075 C>A), RS1000557352 (3:100347073 A>C), RS1000681261 (3:100360730 G>A), RS1000733108 (3:100360956 C>T), RS1000944250 (3:100334999 G>A), RS1000976662 (3:100335297 C>T), RS1000980951 (3:100354385 G>A,T), RS1001009368 (3:100359745 T>G), RS1001022879 (3:100347626 C>T), RS1001246667 (3:100340735 C>T), RS1001583289 (3:100353041 C>T), RS1001596087 (3:100339893 C>G,T)

Disease associations

OMIM: gene MIM:616769 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

StudyTraitp-value
GCST009439_28Age-related cognitive decline (language) (slope of z-scores)6.000000e-07
GCST010002_434Refractive error5.000000e-25

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0007710cognitive decline measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067107 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.58Kd2.637nMCHEMBL5653589
8.56ED502.756nMCHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2148870: Binding affinity to human NIT2 incubated for 45 mins by Kinobead based pull down assaykd0.0026uM

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Adecreases expression, increases expression2
aristolochic acid Idecreases expression1
bisphenol Fincreases expression1
TAK-243increases sumoylation1
dicrotophosdecreases expression1
triphenyl phosphateaffects expression1
trichostatin Aincreases expression1
arseniteaffects binding, increases reaction1
microcystin RRdecreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
nutlin 3affects cotreatment, increases secretion1
ICG 001increases expression1
bisphenol Bincreases expression1
quinocetoneincreases expression1
Grape Seed Proanthocyanidinsaffects cotreatment, decreases expression1
bisphenol Sincreases expression1
jinfukangaffects cotreatment, increases expression1
LDN 193189increases expression, affects cotreatment1
bisphenol AFincreases expression1
Sunitinibdecreases expression1
Acetaminophendecreases expression1
Air Pollutantsdecreases expression, increases abundance1
Atrazineincreases expression1
Benzo(a)pyreneaffects methylation1
Catechinaffects cotreatment, decreases expression1
Cisplatinaffects cotreatment, increases expression1
Dactinomycinaffects cotreatment, increases secretion1
Dichlorodiphenyl Dichloroethyleneincreases expression1
Dexamethasoneincreases expression1
Doxorubicinincreases expression1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5651912BindingBinding affinity to human NIT2 incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_B3CEAbcam HEK293T NIT2 KOTransformed cell lineFemale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.