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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:LPP-CLDN1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LPP-CLDN1
FusionPDB ID: 49555
FusionGDB2.0 ID: 49555
HgeneTgene
Gene symbol

LPP

CLDN1

Gene ID

4026

9076

Gene nameLIM domain containing preferred translocation partner in lipomaclaudin 1
Synonyms-CLD1|ILVASC|SEMP1
Cytomap

3q27.3-q28

3q28

Type of geneprotein-codingprotein-coding
Descriptionlipoma-preferred partnerLIM proteinlipoma preferred partnerclaudin-1senescence-associated epithelial membrane protein 1
Modification date2020031320200313
UniProtAcc

Q93052

Main function of 5'-partner protein: FUNCTION: May play a structural role at sites of cell adhesion in maintaining cell shape and motility. In addition to these structural functions, it may also be implicated in signaling events and activation of gene transcription. May be involved in signal transduction from cell adhesion sites to the nucleus allowing successful integration of signals arising from soluble factors and cell-cell adhesion sites. Also suggested to serve as a scaffold protein upon which distinct protein complexes are assembled in the cytoplasm and in the nucleus. {ECO:0000269|PubMed:10637295}.

P56856

Main function of 5'-partner protein: FUNCTION: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000312675, ENST00000448637, 
ENST00000543006, ENST00000471917, 
ENST00000295522, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score41 X 30 X 15=184505 X 3 X 4=60
# samples 526
** MAII scorelog2(52/18450*10)=-5.14896538280667
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/60*10)=0
Fusion gene context

PubMed: LPP [Title/Abstract] AND CLDN1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LPP [Title/Abstract] AND CLDN1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LPP(188124101)-CLDN1(190030825), # samples:3
Anticipated loss of major functional domain due to fusion event.LPP-CLDN1 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.
LPP-CLDN1 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.
LPP-CLDN1 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.
LPP-CLDN1 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
TgeneCLDN1

GO:0051259

protein complex oligomerization

23704991



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/chr3:188124101/chr3:190030825)
- 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 LPP (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 CLDN1 (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)
ENST00000448637LPPchr3188124101+ENST00000295522CLDN1chr3190030825-332833992751219
ENST00000312675LPPchr3188124101+ENST00000295522CLDN1chr3190030825-3428439123851242
ENST00000543006LPPchr3188124101+ENST00000295522CLDN1chr3190030825-33713829794261

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
ENST00000448637ENST00000295522LPPchr3188124101+CLDN1chr3190030825-0.0150341740.9849658
ENST00000312675ENST00000295522LPPchr3188124101+CLDN1chr3190030825-0.0184263980.98157364
ENST00000543006ENST00000295522LPPchr3188124101+CLDN1chr3190030825-0.0138265310.9861734

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 LPP-CLDN1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LPPchr3188124101CLDN1chr319003082533982KPKYNPYKQPGGEGTLQATRALMVVG
LPPchr3188124101CLDN1chr3190030825382124KPKYNPYKQPGGEGTLQATRALMVVG
LPPchr3188124101CLDN1chr3190030825439105KPKYNPYKQPGGEGTLQATRALMVVG

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Potential FusionNeoAntigen Information of LPP-CLDN1 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.
LPP-CLDN1_188124101_190030825.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)
LPP-CLDN1chr3188124101chr3190030825439HLA-B48:01KQPGGEGTL0.81710.9539716
LPP-CLDN1chr3188124101chr3190030825439HLA-B39:13KQPGGEGTL0.32940.9819716
LPP-CLDN1chr3188124101chr3190030825439HLA-B39:01YKQPGGEGTL0.98290.9653616
LPP-CLDN1chr3188124101chr3190030825439HLA-B38:01YKQPGGEGTL0.97030.9902616
LPP-CLDN1chr3188124101chr3190030825439HLA-B39:13YKQPGGEGTL0.96770.9871616
LPP-CLDN1chr3188124101chr3190030825439HLA-B38:02YKQPGGEGTL0.9670.9897616
LPP-CLDN1chr3188124101chr3190030825439HLA-B15:10YKQPGGEGTL0.960.7196616
LPP-CLDN1chr3188124101chr3190030825439HLA-B48:01YKQPGGEGTL0.78430.9342616
LPP-CLDN1chr3188124101chr3190030825439HLA-B07:10YKQPGGEGTL0.73170.636616
LPP-CLDN1chr3188124101chr3190030825439HLA-B40:01GEGTLQATRAL0.99940.65281122
LPP-CLDN1chr3188124101chr3190030825439HLA-C01:17KQPGGEGTL0.83710.9784716
LPP-CLDN1chr3188124101chr3190030825439HLA-B39:08KQPGGEGTL0.59090.9792716
LPP-CLDN1chr3188124101chr3190030825439HLA-B48:03KQPGGEGTL0.32640.8341716
LPP-CLDN1chr3188124101chr3190030825439HLA-B39:09YKQPGGEGTL0.98730.9119616
LPP-CLDN1chr3188124101chr3190030825439HLA-B39:05YKQPGGEGTL0.96950.9595616
LPP-CLDN1chr3188124101chr3190030825439HLA-B48:03YKQPGGEGTL0.49890.824616
LPP-CLDN1chr3188124101chr3190030825439HLA-C01:03KQPGGEGTL0.9350.9712716
LPP-CLDN1chr3188124101chr3190030825439HLA-C01:02KQPGGEGTL0.86490.9788716
LPP-CLDN1chr3188124101chr3190030825439HLA-B15:73KQPGGEGTL0.80190.968716
LPP-CLDN1chr3188124101chr3190030825439HLA-B15:30KQPGGEGTL0.73150.9755716
LPP-CLDN1chr3188124101chr3190030825439HLA-B48:05KQPGGEGTL0.44580.6192716
LPP-CLDN1chr3188124101chr3190030825439HLA-B40:12KQPGGEGTL0.32640.8341716
LPP-CLDN1chr3188124101chr3190030825439HLA-B40:49KQPGGEGTL0.15070.8233716
LPP-CLDN1chr3188124101chr3190030825439HLA-B40:21KQPGGEGTL0.09690.9294716
LPP-CLDN1chr3188124101chr3190030825439HLA-B39:31YKQPGGEGTL0.98540.9651616
LPP-CLDN1chr3188124101chr3190030825439HLA-B39:02YKQPGGEGTL0.98320.9868616
LPP-CLDN1chr3188124101chr3190030825439HLA-B38:05YKQPGGEGTL0.97030.9902616
LPP-CLDN1chr3188124101chr3190030825439HLA-B39:11YKQPGGEGTL0.92150.9671616
LPP-CLDN1chr3188124101chr3190030825439HLA-B15:09YKQPGGEGTL0.91620.9614616
LPP-CLDN1chr3188124101chr3190030825439HLA-B48:05YKQPGGEGTL0.81020.6016616
LPP-CLDN1chr3188124101chr3190030825439HLA-B40:12YKQPGGEGTL0.49890.824616
LPP-CLDN1chr3188124101chr3190030825439HLA-B40:04GEGTLQATRAL0.99950.81051122
LPP-CLDN1chr3188124101chr3190030825439HLA-B40:49GEGTLQATRAL0.99940.67031122
LPP-CLDN1chr3188124101chr3190030825439HLA-B40:36GEGTLQATRAL0.99930.62371122

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Potential FusionNeoAntigen Information of LPP-CLDN1 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.
LPP-CLDN1_188124101_190030825.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)
LPP-CLDN1chr3188124101chr3190030825439DRB1-0701GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0701GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0703GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0703GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0704GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0704GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0705GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0705GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0706GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0706GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0707GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0707GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0708GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0708GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0709GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0709GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0711GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0711GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0712GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0712GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0713GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0713GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0714GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0714GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0715GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0715GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0716GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0716GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0717GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0717GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-0719GEGTLQATRALMVVG1126
LPP-CLDN1chr3188124101chr3190030825439DRB1-0719GGEGTLQATRALMVV1025
LPP-CLDN1chr3188124101chr3190030825439DRB1-1502KPKYNPYKQPGGEGT015
LPP-CLDN1chr3188124101chr3190030825439DRB1-1508KPKYNPYKQPGGEGT015
LPP-CLDN1chr3188124101chr3190030825439DRB1-1514KPKYNPYKQPGGEGT015
LPP-CLDN1chr3188124101chr3190030825439DRB1-1515KPKYNPYKQPGGEGT015
LPP-CLDN1chr3188124101chr3190030825439DRB1-1519KPKYNPYKQPGGEGT015
LPP-CLDN1chr3188124101chr3190030825439DRB1-1526KPKYNPYKQPGGEGT015
LPP-CLDN1chr3188124101chr3190030825439DRB1-1530KPKYNPYKQPGGEGT015
LPP-CLDN1chr3188124101chr3190030825439DRB1-1531KPKYNPYKQPGGEGT015
LPP-CLDN1chr3188124101chr3190030825439DRB1-1538KPKYNPYKQPGGEGT015
LPP-CLDN1chr3188124101chr3190030825439DRB1-1539KPKYNPYKQPGGEGT015
LPP-CLDN1chr3188124101chr3190030825439DRB1-1544KPKYNPYKQPGGEGT015
LPP-CLDN1chr3188124101chr3190030825439DRB1-1547KPKYNPYKQPGGEGT015

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Fusion breakpoint peptide structures of LPP-CLDN1

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
10700YKQPGGEGTLQATRLPPCLDN1chr3188124101chr3190030825439

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LPP-CLDN1

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-B14:023BVN10700YKQPGGEGTLQATR-6.66111-6.77451
HLA-B14:023BVN10700YKQPGGEGTLQATR-6.49216-7.52746
HLA-B52:013W3910700YKQPGGEGTLQATR-5.57342-5.68682
HLA-B52:013W3910700YKQPGGEGTLQATR-3.59959-4.63489
HLA-A11:014UQ210700YKQPGGEGTLQATR-3.54213-3.65553
HLA-A24:025HGA10700YKQPGGEGTLQATR-7.6647-7.7781
HLA-A24:025HGA10700YKQPGGEGTLQATR-4.05482-5.09012
HLA-B44:053DX810700YKQPGGEGTLQATR-5.24587-5.35927
HLA-B44:053DX810700YKQPGGEGTLQATR-4.91507-5.95037
HLA-A02:016TDR10700YKQPGGEGTLQATR-3.67735-4.71265

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Vaccine Design for the FusionNeoAntigens of LPP-CLDN1

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
LPP-CLDN1chr3188124101chr31900308251122GEGTLQATRALGTGAGGGCACATTGCAAGCAACCCGTGCCTTGA
LPP-CLDN1chr3188124101chr3190030825616YKQPGGEGTLACAAACAACCTGGAGGTGAGGGCACATTGC
LPP-CLDN1chr3188124101chr3190030825716KQPGGEGTLAACAACCTGGAGGTGAGGGCACATTGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
LPP-CLDN1chr3188124101chr3190030825015KPKYNPYKQPGGEGTAACCTAAGTACAACCCATACAAACAACCTGGAGGTGAGGGCACAT
LPP-CLDN1chr3188124101chr31900308251025GGEGTLQATRALMVVGAGGTGAGGGCACATTGCAAGCAACCCGTGCCTTGATGGTGGTTG
LPP-CLDN1chr3188124101chr31900308251126GEGTLQATRALMVVGGTGAGGGCACATTGCAAGCAACCCGTGCCTTGATGGTGGTTGGCA

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Information of the samples that have these potential fusion neoantigens of LPP-CLDN1

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
ESCALPP-CLDN1chr3188124101ENST00000312675chr3190030825ENST00000295522TCGA-LN-A4A2

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Potential target of CAR-T therapy development for LPP-CLDN1

check button Predicted 3D structure. We used RoseTTAFold.
261_LPP-CLDN1_5b579_pred.pdb


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
TgeneCLDN1chr3:188124101chr3:190030825ENST0000029552204116_1360212.0TransmembraneHelical
TgeneCLDN1chr3:188124101chr3:190030825ENST0000029552204164_1840212.0TransmembraneHelical
TgeneCLDN1chr3:188124101chr3:190030825ENST000002955220482_1020212.0TransmembraneHelical

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
LPPchr3188124101ENST00000312675CLDN1chr3190030825ENST00000295522
LPPchr3188124101ENST00000448637CLDN1chr3190030825ENST00000295522
LPPchr3188124101ENST00000543006CLDN1chr3190030825ENST00000295522

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Related Drugs to LPP-CLDN1

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 LPP-CLDN1

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
HgeneLPPC0087031Juvenile-Onset Still Disease1CTD_human
HgeneLPPC3495559Juvenile arthritis1CTD_human
HgeneLPPC3714758Juvenile psoriatic arthritis1CTD_human
HgeneLPPC4552091Polyarthritis, Juvenile, Rheumatoid Factor Negative1CTD_human
HgeneLPPC4704862Polyarthritis, Juvenile, Rheumatoid Factor Positive1CTD_human