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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:BCAN-NTRK1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BCAN-NTRK1
FusionPDB ID: 9146
FusionGDB2.0 ID: 9146
HgeneTgene
Gene symbol

BCAN

NTRK1

Gene ID

63827

4914

Gene namebrevicanneurotrophic receptor tyrosine kinase 1
SynonymsBEHAB|CSPG7MTC|TRK|TRK1|TRKA|Trk-A|p140-TrkA
Cytomap

1q23.1

1q23.1

Type of geneprotein-codingprotein-coding
Descriptionbrevican core proteinbrain-enriched hyaluronan-binding proteinchondroitin sulfate proteoglycan 7chondroitin sulfate proteoglycan BEHABhigh affinity nerve growth factor receptorOncogene TRKTRK1-transforming tyrosine kinase proteingp140trkneurotrophic tyrosine kinase, receptor, type 1tropomyosin-related kinase Atyrosine kinase receptor A
Modification date2020031320200313
UniProtAcc

Q96GW7

Main function of 5'-partner protein: FUNCTION: May play a role in the terminally differentiating and the adult nervous system during postnatal development. Could stabilize interactions between hyaluronan (HA) and brain proteoglycans.

P04629

Main function of 5'-partner protein: FUNCTION: Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1850821, PubMed:1849459, PubMed:1281417, PubMed:8325889, PubMed:15488758, PubMed:22649032, PubMed:17196528, PubMed:27445338). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. {ECO:0000250|UniProtKB:P35739, ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:1849459, ECO:0000269|PubMed:1850821, ECO:0000269|PubMed:22649032, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.; FUNCTION: [Isoform TrkA-III]: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed. {ECO:0000269|PubMed:15488758}.
Ensembl transtripts involved in fusion geneENST idsENST00000329117, ENST00000361588, 
ENST00000531606, ENST00000358660, 
ENST00000368196, ENST00000392302, 
ENST00000524377, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=825 X 24 X 13=7800
# samples 333
** MAII scorelog2(3/8*10)=1.90689059560852log2(33/7800*10)=-4.56293619439116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: BCAN [Title/Abstract] AND NTRK1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BCAN [Title/Abstract] AND NTRK1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)BCAN(156628525)-NTRK1(156844697), # samples:1
BCAN(156628525)-NTRK1(156844698), # samples:1
Anticipated loss of major functional domain due to fusion event.BCAN-NTRK1 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
BCAN-NTRK1 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
BCAN-NTRK1 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
BCAN-NTRK1 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
TgeneNTRK1

GO:0006468

protein phosphorylation

15488758

TgeneNTRK1

GO:0008285

negative regulation of cell proliferation

15488758

TgeneNTRK1

GO:0010976

positive regulation of neuron projection development

15488758

TgeneNTRK1

GO:0018108

peptidyl-tyrosine phosphorylation

2927393

TgeneNTRK1

GO:0043547

positive regulation of GTPase activity

15488758

TgeneNTRK1

GO:0046579

positive regulation of Ras protein signal transduction

15488758

TgeneNTRK1

GO:0046777

protein autophosphorylation

15488758

TgeneNTRK1

GO:0048011

neurotrophin TRK receptor signaling pathway

15488758

TgeneNTRK1

GO:0051092

positive regulation of NF-kappaB transcription factor activity

15488758

TgeneNTRK1

GO:0070374

positive regulation of ERK1 and ERK2 cascade

15488758

TgeneNTRK1

GO:1904646

cellular response to amyloid-beta

11927634



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:156628525/chr1:156844697)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonRetention analysis results of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features, are available here.

check buttonFusion gene breakpoints across BCAN (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across NTRK1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000329117BCANchr1156628525+ENST00000392302NTRK1chr1156844697+4256296433641031255
ENST00000329117BCANchr1156628525+ENST00000368196NTRK1chr1156844697+4312296433641031255
ENST00000329117BCANchr1156628525+ENST00000524377NTRK1chr1156844697+4104296433641031255
ENST00000329117BCANchr1156628525+ENST00000358660NTRK1chr1156844697+4182296433641121258
ENST00000329117BCANchr1156628525+ENST00000392302NTRK1chr1156844698+4256296433641031255
ENST00000329117BCANchr1156628525+ENST00000368196NTRK1chr1156844698+4312296433641031255
ENST00000329117BCANchr1156628525+ENST00000524377NTRK1chr1156844698+4104296433641031255
ENST00000329117BCANchr1156628525+ENST00000358660NTRK1chr1156844698+4182296433641121258

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000329117ENST00000392302BCANchr1156628525+NTRK1chr1156844697+0.0034421760.9965578
ENST00000329117ENST00000368196BCANchr1156628525+NTRK1chr1156844697+0.003353730.9966462
ENST00000329117ENST00000524377BCANchr1156628525+NTRK1chr1156844697+0.0036903490.9963096
ENST00000329117ENST00000358660BCANchr1156628525+NTRK1chr1156844697+0.0044293810.9955706
ENST00000329117ENST00000392302BCANchr1156628525+NTRK1chr1156844698+0.0034421760.9965578
ENST00000329117ENST00000368196BCANchr1156628525+NTRK1chr1156844698+0.003353730.9966462
ENST00000329117ENST00000524377BCANchr1156628525+NTRK1chr1156844698+0.0036903490.9963096
ENST00000329117ENST00000358660BCANchr1156628525+NTRK1chr1156844698+0.0044293810.9955706

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for BCAN-NTRK1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
BCANchr1156628525NTRK1chr11568446972964457FSEEEGKALEEEEKYEDEEEKEEEEE
BCANchr1156628525NTRK1chr11568446982964457FSEEEGKALEEEEKYEDEEEKEEEEE

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Potential FusionNeoAntigen Information of BCAN-NTRK1 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
BCAN-NTRK1_156628525_156844697.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
BCAN-NTRK1chr1156628525chr11568446972964HLA-B15:17KALEEEEKY0.99180.9204615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B58:01KALEEEEKY0.98420.8638615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B58:02KALEEEEKY0.98170.9456615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B15:16KALEEEEKY0.9550.7625615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B35:08KALEEEEKY0.95450.9087615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B35:01KALEEEEKY0.88470.9666615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B15:05KALEEEEKY0.94580.9647615
BCAN-NTRK1chr1156628525chr11568446972964HLA-C15:04KALEEEEKY0.850.8902615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B57:04KALEEEEKY0.98240.7832615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B58:06KALEEEEKY0.98080.8162615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B15:20KALEEEEKY0.9480.9688615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B35:28KALEEEEKY0.93810.9635615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B35:20KALEEEEKY0.90410.9612615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B35:77KALEEEEKY0.88470.9666615
BCAN-NTRK1chr1156628525chr11568446972964HLA-C03:02KALEEEEKY0.86910.9809615
BCAN-NTRK1chr1156628525chr11568446972964HLA-C15:09KALEEEEKY0.850.8902615
BCAN-NTRK1chr1156628525chr11568446972964HLA-B48:02KALEEEEKY0.57380.9596615

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Potential FusionNeoAntigen Information of BCAN-NTRK1 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
BCAN-NTRK1_156628525_156844697.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
BCAN-NTRK1chr1156628525chr11568446972964DRB1-0840GKALEEEEKYEDEEE520
BCAN-NTRK1chr1156628525chr11568446972964DRB1-1381GKALEEEEKYEDEEE520
BCAN-NTRK1chr1156628525chr11568446972964DRB1-1388GKALEEEEKYEDEEE520
BCAN-NTRK1chr1156628525chr11568446972964DRB1-1389GKALEEEEKYEDEEE520
BCAN-NTRK1chr1156628525chr11568446972964DRB1-1389EGKALEEEEKYEDEE419
BCAN-NTRK1chr1156628525chr11568446972964DRB1-1394GKALEEEEKYEDEEE520

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Fusion breakpoint peptide structures of BCAN-NTRK1

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
4108KALEEEEKYEDEEEBCANNTRK1chr1156628525chr11568446972964

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BCAN-NTRK1

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN4108KALEEEEKYEDEEE-7.9962-8.1096
HLA-B14:023BVN4108KALEEEEKYEDEEE-5.70842-6.74372
HLA-B52:013W394108KALEEEEKYEDEEE-6.83737-6.95077
HLA-B52:013W394108KALEEEEKYEDEEE-4.4836-5.5189
HLA-A11:014UQ24108KALEEEEKYEDEEE-10.0067-10.1201
HLA-A11:014UQ24108KALEEEEKYEDEEE-9.03915-10.0745
HLA-A24:025HGA4108KALEEEEKYEDEEE-6.56204-6.67544
HLA-A24:025HGA4108KALEEEEKYEDEEE-5.42271-6.45801
HLA-B44:053DX84108KALEEEEKYEDEEE-7.85648-8.89178
HLA-B44:053DX84108KALEEEEKYEDEEE-5.3978-5.5112
HLA-A02:016TDR4108KALEEEEKYEDEEE-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of BCAN-NTRK1

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
BCAN-NTRK1chr1156628525chr1156844697615KALEEEEKYTCCTGTGTGCCCAGAAGACCTGTCTCG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
BCAN-NTRK1chr1156628525chr1156844697419EGKALEEEEKYEDEECAGATCTCCTGTGTGCCCAGAAGACCTGTCTCGGTGGCTGTGGGC
BCAN-NTRK1chr1156628525chr1156844697520GKALEEEEKYEDEEEATCTCCTGTGTGCCCAGAAGACCTGTCTCGGTGGCTGTGGGCCTG

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Information of the samples that have these potential fusion neoantigens of BCAN-NTRK1

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
GBMBCAN-NTRK1chr1156628525ENST00000329117chr1156844697ENST00000358660TCGA-19-2619

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Potential target of CAR-T therapy development for BCAN-NTRK1

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
TgeneNTRK1chr1:156628525chr1:156844697ENST00000368196816424_4390791.0TransmembraneHelical
TgeneNTRK1chr1:156628525chr1:156844697ENST00000392302917424_4390761.0TransmembraneHelical
TgeneNTRK1chr1:156628525chr1:156844697ENST00000524377917424_4390797.0TransmembraneHelical
TgeneNTRK1chr1:156628525chr1:156844698ENST00000368196816424_4390791.0TransmembraneHelical
TgeneNTRK1chr1:156628525chr1:156844698ENST00000392302917424_4390761.0TransmembraneHelical
TgeneNTRK1chr1:156628525chr1:156844698ENST00000524377917424_4390797.0TransmembraneHelical

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to BCAN-NTRK1

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to BCAN-NTRK1

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
TgeneNTRK1C0020074HSAN Type IV17CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneNTRK1C0238463Papillary thyroid carcinoma3ORPHANET
TgeneNTRK1C0002768Congenital Pain Insensitivity1ORPHANET
TgeneNTRK1C0005586Bipolar Disorder1CTD_human
TgeneNTRK1C0005587Depression, Bipolar1CTD_human
TgeneNTRK1C0017638Glioma1CTD_human
TgeneNTRK1C0020075Hereditary Sensory Autonomic Neuropathy, Type 51CTD_human;ORPHANET
TgeneNTRK1C0024713Manic Disorder1CTD_human
TgeneNTRK1C0027796Neuralgia1CTD_human
TgeneNTRK1C0027819Neuroblastoma1CTD_human
TgeneNTRK1C0033958Psychosis, Brief Reactive1CTD_human
TgeneNTRK1C0033975Psychotic Disorders1CTD_human
TgeneNTRK1C0036337Schizoaffective Disorder1CTD_human
TgeneNTRK1C0036341Schizophrenia1CTD_human
TgeneNTRK1C0036358Schizophreniform Disorders1CTD_human
TgeneNTRK1C0038870Neuralgia, Supraorbital1CTD_human
TgeneNTRK1C0042656Neuralgia, Vidian1CTD_human
TgeneNTRK1C0234247Neuralgia, Atypical1CTD_human
TgeneNTRK1C0234249Neuralgia, Stump1CTD_human
TgeneNTRK1C0259783mixed gliomas1CTD_human
TgeneNTRK1C0273115Lung Injury1CTD_human
TgeneNTRK1C0338831Manic1CTD_human
TgeneNTRK1C0423711Neuralgia, Perineal1CTD_human
TgeneNTRK1C0423712Neuralgia, Iliohypogastric Nerve1CTD_human
TgeneNTRK1C0555198Malignant Glioma1CTD_human
TgeneNTRK1C0598589Inherited neuropathies1GENOMICS_ENGLAND
TgeneNTRK1C0751371Neuralgia, Ilioinguinal1CTD_human
TgeneNTRK1C0751372Nerve Pain1CTD_human
TgeneNTRK1C0751373Paroxysmal Nerve Pain1CTD_human
TgeneNTRK1C0752347Lewy Body Disease1CTD_human
TgeneNTRK1C1833921Familial medullary thyroid carcinoma1CTD_human;GENOMICS_ENGLAND;ORPHANET
TgeneNTRK1C2350344Chronic Lung Injury1CTD_human