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mutLBSgeneDB |
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| Gene summary for NTRK1 |
 Gene summary |
| Basic gene Info. | Gene symbol | NTRK1 |
| Gene name | neurotrophic tyrosine kinase, receptor, type 1 | |
| Synonyms | MTC|TRK|TRK1|TRKA|Trk-A|p140-TrkA | |
| Cytomap | UCSC genome browser: 1q21-q22 | |
| Type of gene | protein-coding | |
| RefGenes | NM_001007792.1, NM_001012331.1,NM_002529.3, | |
| Description | Oncogene TRKTRK1-transforming tyrosine kinase proteingp140trkhigh affinity nerve growth factor receptortropomyosin-related kinase Atyrosine kinase receptor A | |
| Modification date | 20141219 | |
| dbXrefs | MIM : 191315 | |
| HGNC : HGNC | ||
| Ensembl : ENSG00000198400 | ||
| HPRD : 01869 | ||
| Vega : OTTHUMG00000041304 | ||
| Protein | UniProt: P04629 go to UniProt's Cross Reference DB Table | |
| Expression | CleanEX: HS_NTRK1 | |
| BioGPS: 4914 | ||
| Pathway | NCI Pathway Interaction Database: NTRK1 | |
| KEGG: NTRK1 | ||
| REACTOME: NTRK1 | ||
| Pathway Commons: NTRK1 | ||
| Context | iHOP: NTRK1 | |
| ligand binding site mutation search in PubMed: NTRK1 | ||
| UCL Cancer Institute: NTRK1 | ||
| Assigned class in mutLBSgeneDB | A: This gene has a literature evidence and it belongs to targetable_mutLBSgenes. | |
| References showing study about ligand binding site mutation for NTRK1. | 1. Miranda, C., Zanotti, G., Pagliardini, S., Ponzetto, C., Pierotti, M. A., & Greco, A. (2002). Gain of function mutations of RTK conserved residues display differential effects on NTRK1 kinase activity. Oncogene, 21(54), 8334-8339. 12447696 | |
| Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez |
| GO ID | GO Term | PubMed ID | GO:0006468 | protein phosphorylation | 15488758 | GO:0008285 | negative regulation of cell proliferation | 15488758 | GO:0008285 | negative regulation of cell proliferation | 15488758 | GO:0010976 | positive regulation of neuron projection development | 15488758 | GO:0010976 | positive regulation of neuron projection development | 15488758 | GO:0018108 | peptidyl-tyrosine phosphorylation | 15488758 | GO:0032320 | positive regulation of Ras GTPase activity | 15488758 | GO:0032320 | positive regulation of Ras GTPase activity | 15488758 | GO:0045766 | positive regulation of angiogenesis | 15488758 | GO:0046579 | positive regulation of Ras protein signal transduction | 15488758 | GO:0046579 | positive regulation of Ras protein signal transduction | 15488758 | GO:0046777 | protein autophosphorylation | 15488758 | GO:0048011 | neurotrophin TRK receptor signaling pathway | 15488758 | GO:0051092 | positive regulation of NF-kappaB transcription factor activity | 15488758 | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 15488758 | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 15488758 |
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| Ligand binding site mutations for NTRK1 |
| Lollipop-style diagram of mutations at LBS in amino-acid sequence. We represented ligand binding site mutations only. (You can see big image via clicking.)  : non-synonymous mutation on LBS, Circle size denotes number of samples. |
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| Cancer type specific mutLBS sorted by frequency |
| LBS | AAchange of nsSNV | Cancer type | # samples | K544,A542 | V543G | COAD | 1 | R654 | R654H | LUAD | 1 | H648 | R649L | LUAD | 1 | A542 | V541M | LUAD | 1 | F646 | L644M | LUAD | 1 | H648 | R649W | OV | 1 | G517 | G517R | SKCM | 1 | E518 | G519S | SKCM | 1 | C579 | V578I | STAD | 1 | G517 | G517V | UCEC | 1 |
| cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma. |
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| Protein structure related information for NTRK1 |
| Relative protein structure stability change (ΔΔE) using Mupro 1.1 Mupro score denotes assessment of the effect of mutations on thermodynamic stability. (ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability) |
 : nsSNV at non-LBS : nsSNV at LBS |
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| nsSNVs sorted by the relative stability change of protein structure by each mutation Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene. |
| LBS | AAchange of nsSNV | Relative stability change | G517 | G517R | 0.18804961 | H648 | R649L | 0.17000936 | G517 | G517V | 0.16960082 | A542 | V543G | -1.8054481 | K544 | V543G | -1.8054481 | F646 | L644M | -1.3135362 | R654 | R654H | -0.94514378 | C579 | V578I | -0.83449979 | A542 | V541M | -0.76219102 | E518 | G519S | -0.62584889 | H648 | R649W | -0.14927046 |
| (MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132) |
| Structure image for NTRK1 from PDB |
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| Differential gene expression and gene-gene network for NTRK1 |
| Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types |
| Differential co-expressed gene network based on protein-protein interaction data (CePIN) |
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| Phenotype information for NTRK1 |
| Gene level disease information (DisGeNet) |
| Disease ID | Disease name | # PubMed | Association type |
| umls:C0027819 | Neuroblastoma | 43 | AlteredExpression, Biomarker, GeneticVariation |
| umls:C0020074 | INSENSITIVITY TO PAIN, CONGENITAL, WITH ANHIDROSIS | 40 | Biomarker, GeneticVariation |
| umls:C1833921 | Familial medullary thyroid carcinoma | 6 | Biomarker, GeneticVariation |
| umls:C0036341 | Schizophrenia | 5 | Biomarker, GeneticVariation |
| umls:C0027889 | Hereditary Sensory and Autonomic Neuropathies | 2 | Biomarker, GeneticVariation |
| umls:C0017638 | Glioma | 2 | Biomarker |
| umls:C0005586 | Bipolar Disorder | 1 | Biomarker |
| umls:C0752347 | Lewy Body Disease | 1 | Biomarker |
| umls:C0273115 | Lung Injury | 1 | Therapeutic |
| umls:C0027796 | Neuralgia | 1 | Biomarker |
| umls:C0033975 | Psychotic Disorders | 1 | Biomarker |
| Mutation level pathogenic information (ClinVar annotation) |
| Allele ID | AA change | Clinical significance | Origin | Phenotype IDs |
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| Pharmacological information for NTRK1 |
| Gene expression profile of anticancer drug treated cell-lines (CCLE) Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient. |
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| Gene-centered drug-gene interaction network |
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| Drug information targeting mutLBSgene (Approved drugs only) |
| Drug status | DrugBank ID | Name | Type | Drug structure |
| Approved | DB00321 | Amitriptyline | Small molecule |  |
| Approved | DB00619 | Imatinib | Small molecule |  |
| Approved | DB08896 | Regorafenib | Small molecule |  |
| Gene-centered ligand-gene interaction network |
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| Ligands binding to mutated ligand binding site of NTRK1 go to BioLip |
| Ligand ID | Ligand short name | Ligand long name | PDB ID | PDB name | mutLBS | 31W | 1-CYCLOPROPYL-1-[3-(1,3-THIAZOL-2-YL)BENZYL]-3-[4- (TRIFLUOROMETHOXY)PHENYL]UREA | 4pmp | A | A542 K544 | 31X | 4-(NAPHTHALEN-1-YL)-1-[(5-PHENYL-1,2,4-OXADIAZOL-3-YL) METHYL]-1H-PYRROLO[3,2-C]PYRIDINE-2-CARBOXYLIC ACID | 4pms | A | A542 K544 | 31V | N-(3-CYCLOPROPYL-1-PHENYL-1H-PYRAZOL-5-YL)-2-{4-[3- METHOXY-4-(4-METHYL-1H-IMIDAZOL-1-YL)PHENYL]-1H-1,2,3- TRIAZOL-1-YL}ACETAMIDE | 4pmm | A | A542 K544 F646 H648 | V4Z | 5-CHLORANYL-N2-[(1S)-1-(5-FLUORANYLPYRIDIN-2- YL)ETHYL]-N4-(3-PROPAN-2-YLOXY-1H-PYRAZOL-5- YL)PYRIMIDINE-2,4-DIAMINE | 4aoj | A | A542 R654 | V4Z | 5-CHLORANYL-N2-[(1S)-1-(5-FLUORANYLPYRIDIN-2- YL)ETHYL]-N4-(3-PROPAN-2-YLOXY-1H-PYRAZOL-5- YL)PYRIMIDINE-2,4-DIAMINE | 4aoj | B | A542 R654 | V4Z | 5-CHLORANYL-N2-[(1S)-1-(5-FLUORANYLPYRIDIN-2- YL)ETHYL]-N4-(3-PROPAN-2-YLOXY-1H-PYRAZOL-5- YL)PYRIMIDINE-2,4-DIAMINE | 4aoj | C | A542 R654 | 4EK | 6-[(2R)-2-(3-FLUOROPHENYL)PYRROLIDIN-1-YL]-3-(PYRIDIN- 2-YL)IMIDAZO[1,2-B]PYRIDAZINE | 4yne | A | A542 R654 | ZN | ZINC(2+) | 4aoj | A | C579 | ZN | ZINC(2+) | 4aoj | B | C579 | ZN | ZINC(2+) | 4aoj | C | C579 | ZN | ZINC(2+) | 4aoj | A | E518 | ZN | ZINC(2+) | 4aoj | B | E518 | ZN | ZINC(2+) | 4aoj | C | E518 | 31Y | N~4~-[4-(MORPHOLIN-4-YL)PHENYL]-N~6~-(PYRIDIN-3- YLMETHYL)PYRIDO[3,2-D]PYRIMIDINE-4,6-DIAMINE | 4pmt | A | G517 A542 R654 | 4F6 | 4-{6-[(3R)-3-(3-FLUOROPHENYL)MORPHOLIN-4-YL]IMIDAZO[1, 2-B]PYRIDAZIN-3-YL}BENZONITRILE | 4yps | A | G517 A542 R654 |
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| Conservation information for LBS of NTRK1 |
| Multiple alignments for P04629 in multiple species |
| LBS | AA sequence | # species | Species | A542 | DKMLVAVKALK | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | C579 | RFFGVCTEGGP | 2 | Mus musculus, Rattus norvegicus | C579 | RFFGVCTEGRP | 1 | Homo sapiens | C656 | LATRNCLVGQG | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | D596 | YMRHGDLNRFL | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | D668 | VVKIGDFGMSR | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | E515 | IILKWELGEGA | 2 | Mus musculus, Rattus norvegicus | E515 | IVLKWELGEGA | 1 | Homo sapiens | E518 | KWELGEGAFGK | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | E560 | QDFQREAELLT | 2 | Homo sapiens, Mus musculus | E560 | QDFHREAELLT | 1 | Rattus norvegicus | E581 | FGVCTEGGPLL | 2 | Mus musculus, Rattus norvegicus | E581 | FGVCTEGRPLL | 1 | Homo sapiens | E590 | LLMVFEYMRHG | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | F521 | LGEGAFGKVFL | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | F589 | PLLMVFEYMRH | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | F646 | LASLHFVHRDL | 2 | Mus musculus, Rattus norvegicus | F646 | LAGLHFVHRDL | 1 | Homo sapiens | F669 | VKIGDFGMSRD | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | G517 | LKWELGEGAFG | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | G595 | EYMRHGDLNRF | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | G667 | LVVKIGDFGMS | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | G670 | KIGDFGMSRDI | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | H504 | DTCVHHIKRQD | 2 | Mus musculus, Rattus norvegicus | H504 | DACVHHIKRRD | 1 | Homo sapiens | H648 | SLHFVHRDLAT | 2 | Mus musculus, Rattus norvegicus | H648 | GLHFVHRDLAT | 1 | Homo sapiens | I572 | LQHQHIVRFFG | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | I666 | GLVVKIGDFGM | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | K523 | EGAFGKVFLAE | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | K544 | MLVAVKALKEA | 2 | Homo sapiens, Mus musculus | K544 | MLVAVKALKET | 1 | Rattus norvegicus | L516 | ILKWELGEGAF | 2 | Mus musculus, Rattus norvegicus | L516 | VLKWELGEGAF | 1 | Homo sapiens | L563 | QREAELLTMLQ | 2 | Homo sapiens, Mus musculus | L563 | HREAELLTMLQ | 1 | Rattus norvegicus | L564 | REAELLTMLQH | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | L567 | ELLTMLQHQHI | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | L657 | ATRNCLVGQGL | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | M592 | MVFEYMRHGDL | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | M671 | IGDFGMSRDIY | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | N655 | DLATRNCLVGQ | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R593 | VFEYMRHGDLN | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R599 | HGDLNRFLRSH | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R654 | RDLATRNCLVG | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R673 | DFGMSRDIYST | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | V524 | GAFGKVFLAEC | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | V573 | QHQHIVRFFGV | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | Y591 | LMVFEYMRHGD | 3 | Homo sapiens, Mus musculus, Rattus norvegicus |
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