NIT1
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Summary
NIT1 (nitrilase 1, HGNC:7828) is a protein-coding gene on chromosome 1q23.3, encoding Deaminated glutathione amidase (Q86X76). Catalyzes the hydrolysis of the amide bond in N-(4-oxoglutarate)-L-cysteinylglycine (deaminated glutathione), a metabolite repair reaction to dispose of the harmful deaminated glutathione.
This gene encodes a member of the nitrilase protein family with homology to bacterial and plant nitrilases, enzymes that cleave nitriles and organic amides to the corresponding carboxylic acids plus ammonia. Multiple transcript variants encoding different isoforms have been found for this gene.
Source: NCBI Gene 4817 — RefSeq curated summary.
At a glance
- Gene–disease (curated): cerebrovascular disorder (Strong, GenCC)
- Clinical variants (ClinVar): 85 total — 3 pathogenic, 1 likely-pathogenic
- Phenotypes (HPO): 30
- Druggable target: yes
- MANE Select transcript:
NM_005600
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:7828 |
| Approved symbol | NIT1 |
| Name | nitrilase 1 |
| Location | 1q23.3 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000158793 |
| Ensembl biotype | protein_coding |
| OMIM | 604618 |
| Entrez | 4817 |
Gene structure
Transcript identifiers
Ensembl transcripts: 21 — 12 protein_coding_CDS_not_defined, 9 protein_coding
ENST00000368007, ENST00000368008, ENST00000368009, ENST00000392190, ENST00000461376, ENST00000473918, ENST00000477684, ENST00000478277, ENST00000479266, ENST00000479728, ENST00000485594, ENST00000486962, ENST00000491497, ENST00000492411, ENST00000496768, ENST00000496861, ENST00000865250, ENST00000865251, ENST00000935621, ENST00000935622, ENST00000940923
RefSeq mRNA: 4 — MANE Select: NM_005600
NM_001185092, NM_001185093, NM_001185094, NM_005600
CCDS: CCDS1218, CCDS53401, CCDS53402, CCDS53403
Canonical transcript exons
ENST00000368009 — 7 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001446119 | 161120499 | 161121194 |
| ENSE00002229018 | 161118105 | 161118178 |
| ENSE00003460133 | 161119819 | 161119952 |
| ENSE00003499162 | 161118786 | 161118881 |
| ENSE00003536273 | 161120107 | 161120232 |
| ENSE00003588701 | 161119134 | 161119388 |
| ENSE00003646891 | 161119509 | 161119612 |
Expression profiles
Bgee: expression breadth ubiquitous, 287 present calls, max score 97.32.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.5981 / max 188.6881, expressed in 1817 samples.
FANTOM5 promoters (1 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 6199 | 26.5981 | 1817 |
Top tissues by expression
294 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| right adrenal gland cortex | UBERON:0035827 | 97.32 | gold quality |
| right adrenal gland | UBERON:0001233 | 97.26 | gold quality |
| left adrenal gland | UBERON:0001234 | 96.62 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 96.51 | gold quality |
| adrenal cortex | UBERON:0001235 | 96.37 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 96.36 | gold quality |
| right lobe of liver | UBERON:0001114 | 95.96 | gold quality |
| adrenal gland | UBERON:0002369 | 95.92 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 94.37 | gold quality |
| transverse colon | UBERON:0001157 | 94.32 | gold quality |
| duodenum | UBERON:0002114 | 94.18 | gold quality |
| small intestine | UBERON:0002108 | 94.14 | gold quality |
| rectum | UBERON:0001052 | 93.93 | gold quality |
| adenohypophysis | UBERON:0002196 | 93.93 | gold quality |
| granulocyte | CL:0000094 | 93.85 | gold quality |
| adrenal tissue | UBERON:0018303 | 93.83 | gold quality |
| liver | UBERON:0002107 | 93.78 | gold quality |
| body of pancreas | UBERON:0001150 | 93.77 | gold quality |
| jejunal mucosa | UBERON:0000399 | 93.74 | gold quality |
| metanephros cortex | UBERON:0010533 | 93.47 | gold quality |
| right lobe of thyroid gland | UBERON:0001119 | 93.28 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 93.23 | gold quality |
| pituitary gland | UBERON:0000007 | 93.11 | gold quality |
| adult mammalian kidney | UBERON:0000082 | 92.76 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 92.56 | gold quality |
| thyroid gland | UBERON:0002046 | 92.55 | gold quality |
| right uterine tube | UBERON:0001302 | 92.54 | gold quality |
| apex of heart | UBERON:0002098 | 92.52 | gold quality |
| right coronary artery | UBERON:0001625 | 92.46 | gold quality |
| left coronary artery | UBERON:0001626 | 92.43 | gold quality |
Single-cell (SCXA)
Detected in 2 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 6.08 |
| E-MTAB-6386 | no | 353.66 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): MYC
miRNA regulators (miRDB)
42 targeting NIT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-7162-3P | 99.89 | 68.16 | 1682 |
| HSA-MIR-1299 | 99.77 | 71.24 | 2389 |
| HSA-MIR-4320 | 99.75 | 65.80 | 793 |
| HSA-MIR-378G | 99.71 | 64.90 | 1106 |
| HSA-MIR-33A-3P | 99.70 | 70.27 | 3362 |
| HSA-MIR-3059-5P | 99.70 | 69.93 | 2491 |
| HSA-MIR-875-3P | 99.63 | 69.47 | 2548 |
| HSA-MIR-4663 | 99.62 | 65.33 | 957 |
| HSA-MIR-5003-5P | 99.61 | 69.13 | 1624 |
| HSA-MIR-516B-5P | 99.56 | 66.33 | 1495 |
| HSA-MIR-6716-5P | 99.56 | 68.62 | 1244 |
| HSA-MIR-4276 | 99.56 | 67.66 | 2514 |
| HSA-MIR-4437 | 99.52 | 65.29 | 1266 |
| HSA-MIR-203A-3P | 99.49 | 70.56 | 2806 |
| HSA-MIR-6727-3P | 99.49 | 65.92 | 1333 |
| HSA-MIR-4722-3P | 99.35 | 65.22 | 1099 |
| HSA-MIR-6505-3P | 99.34 | 67.39 | 1071 |
| HSA-MIR-5584-3P | 99.23 | 68.79 | 1351 |
| HSA-MIR-8065 | 99.19 | 70.38 | 1289 |
| HSA-MIR-10524-5P | 99.05 | 66.08 | 963 |
| HSA-MIR-939-3P | 98.97 | 65.07 | 2347 |
| HSA-MIR-3124-3P | 98.87 | 68.95 | 2123 |
| HSA-MIR-6829-5P | 98.86 | 65.12 | 1480 |
| HSA-MIR-4755-3P | 98.77 | 65.59 | 1915 |
| HSA-MIR-1301-3P | 98.64 | 68.27 | 1071 |
| HSA-MIR-5047 | 98.64 | 68.62 | 1035 |
| HSA-MIR-660-3P | 98.14 | 66.04 | 1434 |
| HSA-MIR-6881-3P | 98.04 | 68.24 | 1777 |
| HSA-MIR-4303 | 98.01 | 68.13 | 2304 |
| HSA-MIR-146B-3P | 97.83 | 65.29 | 782 |
Literature-anchored findings (GeneRIF, showing 6)
- Nit1 and Fhit share tumor suppressor signaling pathways, while localization of the NIT1 gene at a stable chromosome site explains the paucity of gene alterations and in frequent loss of expression of the NIT1 gene in human malignancies. (PMID:16864578)
- Human NIT1/2 are not involved in the metabolism of vildagliptin. (PMID:25008847)
- Data show that cisplatin response was enhanced in human lung cancer cells when Nit1 was knocked down and mice Nit1-/-:KrasG12D/+ tumors showed increased sensitivity to cisplatin in vivo. (PMID:26967383)
- NIT1 suppresses colorectal cancer cell proliferation through a positive feedback loop between NIT1 and activation of the TGFbeta-Smad2/3 signalling pathway. (PMID:29449642)
- The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit. (PMID:36766695)
- Bi-allelic NIT1 variants cause a brain small vessel disease characterized by movement disorders, massively dilated perivascular spaces, and intracerebral hemorrhage. (PMID:38430071)
Cross-species orthologs
5 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | nit1 | ENSDARG00000070116 |
| mus_musculus | Nit1 | ENSMUSG00000013997 |
| rattus_norvegicus | Nit1 | ENSRNOG00000003881 |
| drosophila_melanogaster | NitFhit | FBGN0024945 |
| caenorhabditis_elegans | WBGENE00003594 |
Paralogs (2): UPB1 (ENSG00000100024), NIT2 (ENSG00000114021)
Protein
Protein identifiers
Deaminated glutathione amidase — Q86X76 (reviewed: Q86X76)
Alternative names: Nitrilase homolog 1
All UniProt accessions (1): Q86X76
UniProt curated annotations — full annotation on UniProt →
Function. Catalyzes the hydrolysis of the amide bond in N-(4-oxoglutarate)-L-cysteinylglycine (deaminated glutathione), a metabolite repair reaction to dispose of the harmful deaminated glutathione. Plays a role in cell growth and apoptosis: loss of expression promotes cell growth, resistance to DNA damage stress and increased incidence to NMBA-induced tumors. Has tumor suppressor properties that enhances the apoptotic responsiveness in cancer cells; this effect is additive to the tumor suppressor activity of FHIT. It is also a negative regulator of primary T-cells.
Subcellular location. Mitochondrion Cytoplasm.
Tissue specificity. Detected in heart, brain, placenta, liver, skeletal muscle, kidney and pancreas.
Disease relevance. Brain small vessel disease 4 (BSVD4) [MIM:621313] An autosomal recessive, adult-onset form of brain small vessel disease, a cerebrovascular disorder with variable manifestations reflecting the location and severity of the vascular defect. BSVD4 patients manifest neurologic symptoms and deficits due to ischemic and/or hemorrhagic events in the brain. Clinical features include progressive movement disorders, such as dystonia, chorea, bradykinesia, tremor as well as gait disturbance and dysarthria, and cognitive decline. Some patients may have psychiatric features. Neuroimaging shows dilated perivascular spaces and cavitating lesions, especially prominent in the basal ganglia and thalamus. The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous. According to Rosetta Stone theory, the existence of a fusion protein in one genome predicts that the separate polypeptides expressed in other organisms function in the same cellular or biochemical pathway. In Drosophila melanogaster and Caenorhabditis elegans, NitFhit is a fusion protein composed of a C-terminal Fhit domain and a domain related to plant and bacterial nitrilase. Major isoform. Based on a naturally occurring readthrough transcript which produces a NIT1-DEDD fusion protein. The last 4 amino acids of this isoform (PVSS) are encoded by the last DEDD exon.
Similarity. Belongs to the carbon-nitrogen hydrolase superfamily. NIT1/NIT2 family.
Isoforms (5)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q86X76-1 | 2 | yes |
| Q86X76-2 | 1, 3 | |
| Q86X76-3 | 4 | |
| Q86X76-4 | 5 | |
| Q86X76-5 | 6 |
RefSeq proteins (4): NP_001172021, NP_001172022, NP_001172023, NP_005591* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001110 | UPF0012_CS | Conserved_site |
| IPR003010 | C-N_Hydrolase | Domain |
| IPR036526 | C-N_Hydrolase_sf | Homologous_superfamily |
| IPR045254 | Nit1/2_C-N_Hydrolase | Domain |
Pfam: PF00795
Catalyzed reactions (Rhea), 1 shown:
- N-(4-oxoglutaryl)-L-cysteinylglycine + H2O = L-cysteinylglycine + 2-oxoglutarate (RHEA:54532)
UniProt features (14 total): splice variant 6, active site 3, transit peptide 1, chain 1, sequence variant 1, sequence conflict 1, domain 1
Structure
Experimental structures (PDB)
0 structures.
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q86X76-F1 | 88.57 | 0.82 |
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): 86 (proton acceptor); 161 (proton donor); 203 (nucleophile)
Function
Pathways and Gene Ontology
Reactome pathways
0 pathways
MSigDB gene sets: 120 (showing top):
DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_AMIDE_METABOLIC_PROCESS, USF_01, BROWNE_HCMV_INFECTION_14HR_DN, DOUGLAS_BMI1_TARGETS_DN, USF_02, GTGACTT_MIR224, DANG_BOUND_BY_MYC, USF2_Q6, MYC_Q2, MYCMAX_03
GO Biological Process (1): obsolete amide catabolic process (GO:0043605)
GO Molecular Function (3): deaminated glutathione amidase activity (GO:0110050), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides (GO:0016811)
GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739)
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| intracellular membrane-bounded organelle | 2 |
| hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides | 1 |
| catalytic activity | 1 |
| hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds | 1 |
| intracellular anatomical structure | 1 |
| cellular anatomical structure | 1 |
| cytoplasm | 1 |
Protein interactions and networks
STRING
1546 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| NIT1 | DEDD | O75618 | 579 |
| NIT1 | INS | P01308 | 564 |
| NIT1 | FFAR1 | O14842 | 419 |
| NIT1 | GPR119 | Q8TDV5 | 419 |
| NIT1 | RPL23 | P23131 | 414 |
| NIT1 | FHIT | P49789 | 405 |
| NIT1 | SLC25A23 | Q9BV35 | 400 |
| NIT1 | GCG | P01275 | 389 |
| NIT1 | POLA2 | Q14181 | 386 |
| NIT1 | TDP2 | O95551 | 371 |
| NIT1 | AGPAT1 | Q99943 | 370 |
| NIT1 | RPL12 | P30050 | 368 |
| NIT1 | OXCT1 | P55809 | 364 |
| NIT1 | SLC27A4 | Q6P1M0 | 356 |
| NIT1 | C3orf38 | Q5JPI3 | 350 |
IntAct
24 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| SLC31A1 | C2orf72 | psi-mi:“MI:0914”(association) | 0.530 |
| LRRC57 | NIT1 | psi-mi:“MI:0915”(physical association) | 0.400 |
| NIT1 | ZFYVE9 | psi-mi:“MI:0915”(physical association) | 0.370 |
| SIRT4 | VWA8 | psi-mi:“MI:0914”(association) | 0.350 |
| NDUFA11 | NDUFS8 | psi-mi:“MI:0914”(association) | 0.350 |
| NIT1 | NDUFS6 | psi-mi:“MI:0914”(association) | 0.350 |
| SDHAF4 | GPX4 | psi-mi:“MI:0914”(association) | 0.350 |
| NIT1 | PMPCB | psi-mi:“MI:0914”(association) | 0.350 |
| ZNRD2 | KRBA1 | psi-mi:“MI:0914”(association) | 0.350 |
| NIT1 | NUDT19 | psi-mi:“MI:0914”(association) | 0.350 |
| HOXC5 | PDLIM1 | psi-mi:“MI:0914”(association) | 0.350 |
| ISOC2 | GTPBP1 | psi-mi:“MI:0914”(association) | 0.350 |
| CAMK2A | SMCHD1 | psi-mi:“MI:0914”(association) | 0.350 |
| SHARPIN | ZNF609 | psi-mi:“MI:0914”(association) | 0.350 |
| RTP2 | GPAA1 | psi-mi:“MI:0914”(association) | 0.350 |
| IFT74 | ZC3HAV1 | psi-mi:“MI:0914”(association) | 0.350 |
| PDAP1 | NIT1 | psi-mi:“MI:0914”(association) | 0.350 |
| FGFBP2 | RAB4A | psi-mi:“MI:0914”(association) | 0.350 |
| SMPD2 | A2ML1 | psi-mi:“MI:0914”(association) | 0.350 |
| NIT1 | XRCC6 | psi-mi:“MI:0915”(physical association) | 0.000 |
BioGRID (88): CUX1 (Co-fractionation), NIT1 (Co-fractionation), NIT1 (Co-fractionation), NIT1 (Co-fractionation), NIT1 (Co-fractionation), NIT1 (Co-fractionation), NIT1 (Co-fractionation), NIT1 (Co-fractionation), NIT1 (Co-fractionation), PSMG4 (Co-fractionation), NIT1 (Affinity Capture-MS), NIT1 (Affinity Capture-MS), NIT1 (Affinity Capture-MS), SLC25A27 (Affinity Capture-MS), IBA57 (Affinity Capture-MS)
ESM2 similar proteins: A0MTA1, A1YES6, A1YFZ3, A2T6Y4, A2T7I6, A5WVX1, B4FAT0, O54747, O94903, P0A2X3, P0A2X4, P13051, P23196, P26882, P27695, P28339, P28340, P28352, P36776, P43138, P52431, P97283, P97931, Q08752, Q08DF7, Q0J705, Q0V9S0, Q16775, Q32LH4, Q3B7M2, Q3T0G5, Q3TIU4, Q4P1V1, Q4R5U5, Q4R6C1, Q59HJ6, Q5R4Z1, Q5XIP6, Q5ZI23, Q653S9
Diamond homologs: A0A140NCB4, O31664, O59829, O76463, O94660, P0DP63, P0DP64, P0DP66, P0DP67, P0DP68, P47016, P55175, P55178, P58054, P9WJ00, P9WJ01, Q32LH4, Q557J5, Q7TQ94, Q86X76, Q8VDK1, Q93NG1, A0A140NDS5, P0DP65, P55176, P55177, Q47679, Q8RUF8, O76464, Q10166, Q28IE5, Q2T9R6, Q4VBV9, Q54JM9, Q5R4L6, Q6INI7, Q6IR61, Q75SP7, Q94JV5, Q9JHW2
SIGNOR signaling
0 interactions.
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 33 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| Aerobic respiration and respiratory electron transport | 5 | 21.1× | 4e-04 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
85 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 3 |
| Likely pathogenic | 1 |
| Uncertain significance | 70 |
| Likely benign | 2 |
| Benign | 1 |
Top pathogenic / likely-pathogenic (4)
| Variant ID | HGVS | Classification |
|---|---|---|
| 4076955 | NM_005600.3(NIT1):c.198_199del (p.Cys67_Ala68insTer) | Pathogenic |
| 4076956 | NIT1, 457G-A | Pathogenic |
| 4076957 | NIT1, 1-BP DUP, 670A | Pathogenic |
| 3256938 | NM_005600.3(NIT1):c.591+2T>G | Likely pathogenic |
SpliceAI
1600 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 1:161119366:G:GT | donor_gain | 1.0000 |
| 1:161120105:A:AG | acceptor_gain | 1.0000 |
| 1:161120105:A:T | acceptor_loss | 1.0000 |
| 1:161120105:AGATT:A | acceptor_gain | 1.0000 |
| 1:161120106:G:GT | acceptor_gain | 1.0000 |
| 1:161120106:GA:G | acceptor_gain | 1.0000 |
| 1:161120106:GAT:G | acceptor_gain | 1.0000 |
| 1:161120106:GATT:G | acceptor_gain | 1.0000 |
| 1:161120106:GATTG:G | acceptor_gain | 1.0000 |
| 1:161120228:GGGAG:G | donor_gain | 1.0000 |
| 1:161120229:GGAG:G | donor_gain | 1.0000 |
| 1:161120229:GGAGG:G | donor_gain | 1.0000 |
| 1:161120230:GAGG:G | donor_gain | 1.0000 |
| 1:161120231:AGGT:A | donor_loss | 1.0000 |
| 1:161120232:GGTAA:G | donor_loss | 1.0000 |
| 1:161120233:G:A | donor_loss | 1.0000 |
| 1:161120234:T:A | donor_loss | 1.0000 |
| 1:161122521:TGT:T | acceptor_gain | 1.0000 |
| 1:161122522:GTC:G | acceptor_loss | 1.0000 |
| 1:161122523:TCTG:T | acceptor_loss | 1.0000 |
| 1:161122524:C:CC | acceptor_gain | 1.0000 |
| 1:161122527:T:TC | acceptor_gain | 1.0000 |
| 1:161122534:C:CT | acceptor_gain | 1.0000 |
| 1:161122535:A:T | acceptor_gain | 1.0000 |
| 1:161123068:T:TA | donor_gain | 1.0000 |
| 1:161123833:TCTCA:T | donor_loss | 1.0000 |
| 1:161123834:CTCAC:C | donor_loss | 1.0000 |
| 1:161123835:TCA:T | donor_loss | 1.0000 |
| 1:161123836:CA:C | donor_loss | 1.0000 |
| 1:161123838:C:CA | donor_loss | 1.0000 |
AlphaMissense
2087 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 1:161120137:T:C | F208L | 0.996 |
| 1:161120139:C:A | F208L | 0.996 |
| 1:161120139:C:G | F208L | 0.996 |
| 1:161120200:T:C | F229L | 0.994 |
| 1:161120202:T:A | F229L | 0.994 |
| 1:161120202:T:G | F229L | 0.994 |
| 1:161119844:G:C | K161N | 0.993 |
| 1:161119844:G:T | K161N | 0.993 |
| 1:161120595:A:C | S272R | 0.993 |
| 1:161120597:C:A | S272R | 0.993 |
| 1:161120597:C:G | S272R | 0.993 |
| 1:161120129:A:T | D205V | 0.991 |
| 1:161120180:T:A | I222K | 0.989 |
| 1:161120518:C:A | A246D | 0.989 |
| 1:161119843:A:C | K161T | 0.987 |
| 1:161120128:G:C | D205H | 0.987 |
| 1:161120229:G:C | W238C | 0.987 |
| 1:161120229:G:T | W238C | 0.987 |
| 1:161120515:G:C | R245P | 0.987 |
| 1:161120616:G:A | G279R | 0.987 |
| 1:161120616:G:C | G279R | 0.987 |
| 1:161120128:G:T | D205Y | 0.986 |
| 1:161120129:A:C | D205A | 0.986 |
| 1:161120138:T:C | F208S | 0.986 |
| 1:161119385:C:A | A117D | 0.985 |
| 1:161120517:G:C | A246P | 0.985 |
| 1:161120617:G:T | G279V | 0.985 |
| 1:161119184:C:A | A50D | 0.984 |
| 1:161120545:C:A | A255E | 0.984 |
| 1:161119289:C:A | P85H | 0.983 |
dbSNP variants (sampled 300 via entrez): RS1000050394 (1:161119877 G>A), RS1000893680 (1:161121235 C>A,T), RS1001560087 (1:161124615 G>A), RS1001596000 (1:161124893 C>T), RS1001725631 (1:161124025 A>G), RS1001895572 (1:161122829 C>T), RS1001961229 (1:161116475 C>T), RS1001988211 (1:161124519 C>T), RS1002479018 (1:161116776 T>C), RS1002635454 (1:161118985 G>T), RS1003161207 (1:161119384 G>A), RS1003934925 (1:161119356 G>A), RS1004003101 (1:161120806 C>A,G,T), RS1004474874 (1:161118902 C>T), RS1004517170 (1:161124712 A>G)
Disease associations
OMIM: gene MIM:604618 | disease phenotypes: MIM:621313
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| cerebrovascular disorder | Strong | Autosomal recessive |
Mondo (2): brain small vessel disease 4 (MONDO:0979873), cerebrovascular disorder (MONDO:0011057)
Orphanet (0):
HPO phenotypes
30 total (30 of 30 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0000007 | Autosomal recessive inheritance |
| HP:0000709 | Psychosis |
| HP:0000716 | Depression |
| HP:0001256 | Mild intellectual disability |
| HP:0001257 | Spasticity |
| HP:0001259 | Coma |
| HP:0001260 | Dysarthria |
| HP:0001269 | Hemiparesis |
| HP:0001279 | Syncope |
| HP:0001288 | Gait disturbance |
| HP:0001297 | Stroke |
| HP:0001332 | Dystonia |
| HP:0001337 | Tremor |
| HP:0001342 | Cerebral hemorrhage |
| HP:0002067 | Bradykinesia |
| HP:0002072 | Chorea |
| HP:0002140 | Ischemic stroke |
| HP:0002197 | Generalized-onset seizure |
| HP:0002353 | EEG abnormality |
| HP:0002445 | Tetraplegia |
| HP:0003596 | Middle age onset |
| HP:0006799 | Basal ganglia cysts |
| HP:0011462 | Young adult onset |
| HP:0011463 | Childhood onset |
| HP:0011942 | Increased urinary sulfite level |
| HP:0012378 | Fatigue |
| HP:0012520 | Dilation of Virchow-Robin spaces |
| HP:0032325 | Lacunar stroke |
| HP:0100543 | Cognitive impairment |
| HP:0100753 | Schizophrenia |
GWAS associations
0 associations (top):
MeSH disease descriptors (1)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D002561 | Cerebrovascular Disorders | C10.228.140.300; C14.907.253 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL4295883 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
CTD chemical–gene interactions
53 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| sodium arsenite | affects cotreatment, decreases expression, increases abundance, increases expression | 4 |
| Smoke | decreases expression | 2 |
| aristolochic acid I | decreases expression | 1 |
| bisphenol F | increases expression | 1 |
| 2,4,6-tribromophenol | decreases expression | 1 |
| bufotalin | decreases expression | 1 |
| methylmercuric chloride | decreases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| alpha-pinene | affects cotreatment, increases expression, increases abundance | 1 |
| decabromobiphenyl ether | decreases expression | 1 |
| trichostatin A | affects expression | 1 |
| beta-lapachone | increases expression | 1 |
| tetrabromobisphenol A | increases expression | 1 |
| potassium chromate(VI) | decreases expression, affects cotreatment | 1 |
| methacrylaldehyde | affects cotreatment, increases expression, increases abundance | 1 |
| epigallocatechin gallate | affects cotreatment, decreases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| fenpyroximate | decreases expression | 1 |
| 4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide | decreases expression | 1 |
| ICG 001 | decreases expression | 1 |
| bisphenol B | increases expression | 1 |
| abrine | increases expression | 1 |
| 2,2’,4,4’-tetrabromodiphenyl ether | decreases expression | 1 |
| pyrachlostrobin | decreases expression | 1 |
| pentabrominated diphenyl ether 100 | decreases expression | 1 |
| hexabrominated diphenyl ether 153 | decreases expression | 1 |
| jinfukang | increases expression | 1 |
| picoxystrobin | decreases expression | 1 |
| NSC 689534 | affects binding, increases expression | 1 |
ChEMBL screening assays
2 unique, capped per target: 2 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL4118728 | Binding | Binding affinity to NIT1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay | Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem |
Clinical trials (associated diseases)
300 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00004727 | PHASE4 | COMPLETED | Antiplatelet Therapy to Prevent Stroke in African Americans |
| NCT00029172 | PHASE4 | COMPLETED | Treatment for Post-Stroke Depression |
| NCT00079638 | PHASE4 | COMPLETED | Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL |
| NCT00101543 | PHASE4 | COMPLETED | Gait Training For Acute Stroke: Functional Neuromuscular Stimulation (FNS) and Weight Supported Treadmill Training |
| NCT00102869 | PHASE4 | COMPLETED | Dopaminergic Enhancement of Learning and Memory in Aphasia |
| NCT00106886 | PHASE4 | UNKNOWN | HOPE-2 Study (Heart Outcomes Prevention Evaluation-2 Study) |
| NCT00108706 | PHASE4 | UNKNOWN | Acute Candesartan Cilexetil Outcomes Stroke Trial (ACCOST) |
| NCT00126087 | PHASE4 | TERMINATED | Potentiation of Procedural Motor Learning in Health and Disease |
| NCT00130039 | PHASE4 | COMPLETED | Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II |
| NCT00149227 | PHASE4 | COMPLETED | Add-on Effects of Valsartan on Morbi- Mortality (KYOTO HEART Study) |
| NCT00153062 | PHASE4 | COMPLETED | PRoFESS - Prevention Regimen For Effectively Avoiding Second Strokes |
| NCT00153946 | PHASE4 | COMPLETED | Edaravone and Argatroban Stroke Therapy Study for Acute Ischemic Stroke |
| NCT00163150 | PHASE4 | COMPLETED | Vasomotor Reactivity In Cerebral Small Vessel Disease And New Approach To Treat Lacunar Stroke |
| NCT00177424 | PHASE4 | TERMINATED | Sertraline for Preventing Post-stroke Depression and Improving Rehabilitation Outcomes |
| NCT00178646 | PHASE4 | COMPLETED | Comparative Efficacy of Three Preparations of Botox-A in Treating Spasticity |
| NCT00196690 | PHASE4 | COMPLETED | Donepezil in Chronic Poststroke Aphasia: a Randomized Controlled Trial |
| NCT00196703 | PHASE4 | UNKNOWN | Memantine and Constraint-Induced Language Therapy in Chronic Poststroke Aphasia:A Randomized Controlled Trial |
| NCT00200356 | PHASE4 | COMPLETED | Edaravone-Sodium Ozagrel Comparative Post-Marketing Study on Acute Ischemic Stroke |
| NCT00216411 | PHASE4 | COMPLETED | Effects on Quality of Life Following Dysport Treatment in Post-stroke Spasticity of the Arm |
| NCT00227994 | PHASE4 | COMPLETED | Acetylcholinesterase Inhibitors to Improve Cognitive Function and Overall Rehabilitation After a Stroke |
| NCT00234065 | PHASE4 | COMPLETED | Post-marketing Study of Cilostazol (Cilostazol Stroke Prevention Study 2) |
| NCT00234546 | PHASE4 | COMPLETED | Asian Botulinum Clinical Trial Designed for Early Stroke Spasticity |
| NCT00247533 | PHASE4 | UNKNOWN | Cerebral Artery Stenosis, Coronary Artery Disease and Arrhythmia |
| NCT00263393 | PHASE4 | COMPLETED | Rural Andhra Pradesh Cardiovascular Prevention Study (RAPCAPS) |
| NCT00272454 | PHASE4 | COMPLETED | Cilostazol in Acute Ischemic Stroke Treatment (CAIST) |
| NCT00279149 | PHASE4 | COMPLETED | TRUST-tPA: Therapeutic Trial Evaluating Efficacy of Telemedicine (TELESTROKE) of Patients With Acute Stroke |
| NCT00287508 | PHASE4 | COMPLETED | Emboshield® and Xact® Post Approval Carotid Stent Trial (The EXACT Study) |
| NCT00327418 | PHASE4 | COMPLETED | CARDS Is Designed To Show If Lowering Cholesterol With Atorvastatin In Type 2 Diabetics Without CV Disease Reduces The Risk Of CV Events |
| NCT00327691 | PHASE4 | COMPLETED | A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels |
| NCT00351806 | PHASE4 | COMPLETED | AISTCM-Outcome Measurement of Acute Ischemic Stroke With Traditional Chinese Medicine |
| NCT00386191 | PHASE4 | COMPLETED | Safety and Efficacy of Clopidogrel for Cerebral Infarction Treatment |
| NCT00396058 | PHASE4 | TERMINATED | The Effect of Methylphenidate on Motor Learning in Stroke Patients |
| NCT00412867 | PHASE4 | COMPLETED | Post-marketing Clinical Study of Alteplase for Acute Ischemic Stroke (Japan Alteplase Clinical Trial Ⅱ:J-ACT Ⅱ) |
| NCT00442325 | PHASE4 | COMPLETED | Benefits Of Using Various Starting Doses Of Atorvastatin On Achievement Of Cholesterol Targets |
| NCT00442845 | PHASE4 | COMPLETED | Establish The Benefits Of Using Various Starting Doses Of Atorvastatin On Achievement Of Cholesterol Targets (ACTFAST) |
| NCT00446641 | PHASE4 | COMPLETED | Overcome Biochemical Aspirin Resistance Through Cilostazol Combination |
| NCT00468923 | PHASE4 | COMPLETED | Heart Outcomes Prevention Evaluation-3 |
| NCT00548223 | PHASE4 | COMPLETED | The Secondary Prevention Trial for Ischemic Stroke With DengzhanShengmai Capsule |
| NCT00552916 | PHASE4 | UNKNOWN | Functional Electrical Stimulation (FES) Assisted Walking: Enhancement of Walking Function After Stroke |
| NCT00559988 | PHASE4 | TERMINATED | Combined Use of BIOTRONIK Home Monitoring and Predefined Anticoagulation to Reduce Stroke Risk |
Related Atlas pages
- Associated diseases: cerebrovascular disorder
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): brain small vessel disease 4, cerebrovascular disorder