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Center for Computational Systems Medicine level2
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:RNF213-IL22RA1

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RNF213-IL22RA1
FusionPDB ID: 74977
FusionGDB2.0 ID: 74977
HgeneTgene
Gene symbol

RNF213

IL22RA1

Gene ID

57674

58985

Gene namering finger protein 213interleukin 22 receptor subunit alpha 1
SynonymsALO17|C17orf27|KIAA1618|MYMY2|MYSTR|NET57CRF2-9|IL22R|IL22R1
Cytomap

17q25.3

1p36.11

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase RNF213ALK lymphoma oligomerization partner on chromosome 17RING-type E3 ubiquitin transferase RNF213mysterininterleukin-22 receptor subunit alpha-1IL-22 receptor subunit alpha-1IL-22R-alpha-1IL-22RA1cytokine receptor class-II member 9cytokine receptor family 2 member 9interleukin 22 receptor, alpha 1zcytoR11
Modification date2020031320200313
UniProtAcc

Q63HN8

Q8N6P7

Ensembl transtripts involved in fusion geneENST idsENST00000319921, ENST00000456466, 
ENST00000508628, ENST00000582970, 
ENST00000336301, ENST00000427003, 
ENST00000270800, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score34 X 32 X 16=174082 X 2 X 2=8
# samples 412
** MAII scorelog2(41/17408*10)=-5.40798274174489
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Context (manual curation of fusion genes in FusionPDB)

PubMed: RNF213 [Title/Abstract] AND IL22RA1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RNF213(78237577)-IL22RA1(24465204), # samples:4
Anticipated loss of major functional domain due to fusion event.RNF213-IL22RA1 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.
RNF213-IL22RA1 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.
RNF213-IL22RA1 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.
RNF213-IL22RA1 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
HgeneRNF213

GO:0016567

protein ubiquitination

21799892

HgeneRNF213

GO:0051260

protein homooligomerization

24658080|26126547

HgeneRNF213

GO:0051865

protein autoubiquitination

21799892


check buttonFusion gene breakpoints across RNF213 (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 IL22RA1 (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 Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4BLCATCGA-GV-A3JZ-01ARNF213chr17

78237577

-IL22RA1chr1

24465204

-
ChimerDB4BLCATCGA-GV-A3JZ-01ARNF213chr17

78237577

+IL22RA1chr1

24465204

-
ChimerDB4BLCATCGA-GV-A3JZRNF213chr17

78237577

+IL22RA1chr1

24465204

-


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Fusion ORF Analysis


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)
ENST00000508628RNF213chr1778237577+ENST00000270800IL22RA1chr124465204-29582421451923592
ENST00000456466RNF213chr1778237577+ENST00000270800IL22RA1chr124465204-29562401431921592
ENST00000582970RNF213chr1778237577+ENST00000270800IL22RA1chr124465204-29562401431921592
ENST00000319921RNF213chr1778237577+ENST00000270800IL22RA1chr124465204-29542381411919592

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
ENST00000508628ENST00000270800RNF213chr1778237577+IL22RA1chr124465204-0.0198235230.98017645
ENST00000456466ENST00000270800RNF213chr1778237577+IL22RA1chr124465204-0.0199547020.9800454
ENST00000582970ENST00000270800RNF213chr1778237577+IL22RA1chr124465204-0.0199547020.9800454
ENST00000319921ENST00000270800RNF213chr1778237577+IL22RA1chr124465204-0.0199036430.9800963

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Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>74977_74977_1_RNF213-IL22RA1_RNF213_chr17_78237577_ENST00000319921_IL22RA1_chr1_24465204_ENST00000270800_length(amino acids)=592AA_BP=29
MECPSCQHVSKEETPKFCSQCGERLPPAAPIAAHAPEDPSDLLQHVKFQSSNFENILTWDSGPEGTPDTVYSIEYKTYGERDWVAKKGCQ
RITRKSCNLTVETGNLTELYYARVTAVSAGGRSATKMTDRFSSLQHTTLKPPDVTCISKVRSIQMIVHPTPTPIRAGDGHRLTLEDIFHD
LFYHLELQVNRTYQMHLGGKQREYEFFGLTPDTEFLGTIMICVPTWAKESAPYMCRVKTLPDRTWTYSFSGAFLFSMGFLVAVLCYLSYR
YVTKPPAPPNSLNVQRVLTFQPLRFIQEHVLIPVFDLSGPSSLAQPVQYSQIRVSGPREPAGAPQRHSLSEITYLGQPDISILQPSNVPP
PQILSPLSYAPNAAPEVGPPSYAPQVTPEAQFPFYAPQAISKVQPSSYAPQATPDSWPPSYGVCMEGSGKDSPTGTLSSPKHLRPKGQLQ
KEPPAGSCMLGGLSLQEVTSLAMEESQEAKSLHQPLGICTDRTSDPNVLHSGEEGTPQYLKGQLPLLSSVQIEGHPMSLPLQPPSRPCSP

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>74977_74977_2_RNF213-IL22RA1_RNF213_chr17_78237577_ENST00000456466_IL22RA1_chr1_24465204_ENST00000270800_length(amino acids)=592AA_BP=29
MECPSCQHVSKEETPKFCSQCGERLPPAAPIAAHAPEDPSDLLQHVKFQSSNFENILTWDSGPEGTPDTVYSIEYKTYGERDWVAKKGCQ
RITRKSCNLTVETGNLTELYYARVTAVSAGGRSATKMTDRFSSLQHTTLKPPDVTCISKVRSIQMIVHPTPTPIRAGDGHRLTLEDIFHD
LFYHLELQVNRTYQMHLGGKQREYEFFGLTPDTEFLGTIMICVPTWAKESAPYMCRVKTLPDRTWTYSFSGAFLFSMGFLVAVLCYLSYR
YVTKPPAPPNSLNVQRVLTFQPLRFIQEHVLIPVFDLSGPSSLAQPVQYSQIRVSGPREPAGAPQRHSLSEITYLGQPDISILQPSNVPP
PQILSPLSYAPNAAPEVGPPSYAPQVTPEAQFPFYAPQAISKVQPSSYAPQATPDSWPPSYGVCMEGSGKDSPTGTLSSPKHLRPKGQLQ
KEPPAGSCMLGGLSLQEVTSLAMEESQEAKSLHQPLGICTDRTSDPNVLHSGEEGTPQYLKGQLPLLSSVQIEGHPMSLPLQPPSRPCSP

--------------------------------------------------------------

>74977_74977_3_RNF213-IL22RA1_RNF213_chr17_78237577_ENST00000508628_IL22RA1_chr1_24465204_ENST00000270800_length(amino acids)=592AA_BP=29
MECPSCQHVSKEETPKFCSQCGERLPPAAPIAAHAPEDPSDLLQHVKFQSSNFENILTWDSGPEGTPDTVYSIEYKTYGERDWVAKKGCQ
RITRKSCNLTVETGNLTELYYARVTAVSAGGRSATKMTDRFSSLQHTTLKPPDVTCISKVRSIQMIVHPTPTPIRAGDGHRLTLEDIFHD
LFYHLELQVNRTYQMHLGGKQREYEFFGLTPDTEFLGTIMICVPTWAKESAPYMCRVKTLPDRTWTYSFSGAFLFSMGFLVAVLCYLSYR
YVTKPPAPPNSLNVQRVLTFQPLRFIQEHVLIPVFDLSGPSSLAQPVQYSQIRVSGPREPAGAPQRHSLSEITYLGQPDISILQPSNVPP
PQILSPLSYAPNAAPEVGPPSYAPQVTPEAQFPFYAPQAISKVQPSSYAPQATPDSWPPSYGVCMEGSGKDSPTGTLSSPKHLRPKGQLQ
KEPPAGSCMLGGLSLQEVTSLAMEESQEAKSLHQPLGICTDRTSDPNVLHSGEEGTPQYLKGQLPLLSSVQIEGHPMSLPLQPPSRPCSP

--------------------------------------------------------------

>74977_74977_4_RNF213-IL22RA1_RNF213_chr17_78237577_ENST00000582970_IL22RA1_chr1_24465204_ENST00000270800_length(amino acids)=592AA_BP=29
MECPSCQHVSKEETPKFCSQCGERLPPAAPIAAHAPEDPSDLLQHVKFQSSNFENILTWDSGPEGTPDTVYSIEYKTYGERDWVAKKGCQ
RITRKSCNLTVETGNLTELYYARVTAVSAGGRSATKMTDRFSSLQHTTLKPPDVTCISKVRSIQMIVHPTPTPIRAGDGHRLTLEDIFHD
LFYHLELQVNRTYQMHLGGKQREYEFFGLTPDTEFLGTIMICVPTWAKESAPYMCRVKTLPDRTWTYSFSGAFLFSMGFLVAVLCYLSYR
YVTKPPAPPNSLNVQRVLTFQPLRFIQEHVLIPVFDLSGPSSLAQPVQYSQIRVSGPREPAGAPQRHSLSEITYLGQPDISILQPSNVPP
PQILSPLSYAPNAAPEVGPPSYAPQVTPEAQFPFYAPQAISKVQPSSYAPQATPDSWPPSYGVCMEGSGKDSPTGTLSSPKHLRPKGQLQ
KEPPAGSCMLGGLSLQEVTSLAMEESQEAKSLHQPLGICTDRTSDPNVLHSGEEGTPQYLKGQLPLLSSVQIEGHPMSLPLQPPSRPCSP

--------------------------------------------------------------

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Fusion Protein Functional Features


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/chr17:78237577/chr1:24465204)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
RNF213

Q63HN8

IL22RA1

Q8N6P7

FUNCTION: Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity (PubMed:21799892, PubMed:26126547, PubMed:26278786, PubMed:26766444, PubMed:30705059, PubMed:32139119, PubMed:34012115). Acts as a key immune sensor by catalyzing ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc-finger: restricts the proliferation of cytosolic bacteria, such as Salmonella, by generating the bacterial ubiquitin coat through the ubiquitination of LPS (PubMed:34012115). Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains (PubMed:34012115). Ubiquitination of LPS triggers cell-autonomous immunity, such as antibacterial autophagy, leading to degradation of the microbial invader (PubMed:34012115). Involved in lipid metabolism by regulating fat storage and lipid droplet formation; act by inhibiting the lipolytic process (PubMed:30705059). Also regulates lipotoxicity by inhibiting desaturation of fatty acids (PubMed:30846318). Also acts as an E3 ubiquitin-protein ligase via its RING-type zinc finger: mediates 'Lys-63'-linked ubiquitination of target proteins (PubMed:32139119, PubMed:33842849). Involved in the non-canonical Wnt signaling pathway in vascular development: acts by mediating ubiquitination and degradation of FLNA and NFATC2 downstream of RSPO3, leading to inhibit the non-canonical Wnt signaling pathway and promoting vessel regression (PubMed:26766444). Also has ATPase activity; ATPase activity is required for ubiquitination of LPS (PubMed:34012115). {ECO:0000269|PubMed:21799892, ECO:0000269|PubMed:26126547, ECO:0000269|PubMed:26278786, ECO:0000269|PubMed:26766444, ECO:0000269|PubMed:30705059, ECO:0000269|PubMed:30846318, ECO:0000269|PubMed:32139119, ECO:0000269|PubMed:33842849, ECO:0000269|PubMed:34012115}.FUNCTION: Component of the receptor for IL20, IL22 and IL24. Component of IL22 receptor formed by IL22RA1 and IL10RB enabling IL22 signaling via JAK/STAT pathways. IL22 also induces activation of MAPK1/MAPK3 and Akt kinases pathways. Component of one of the receptor for IL20 and IL24 formed by IL22RA1 and IL20RB also signaling through STATs activation. Mediates IL24 antiangiogenic activity as well as IL24 inhibitory effect on endothelial cell tube formation and differentiation. {ECO:0000269|PubMed:11035029, ECO:0000269|PubMed:11564763, ECO:0000269|PubMed:11706020, ECO:0000269|PubMed:12351624, ECO:0000269|PubMed:12941841, ECO:0000269|PubMed:17204547}.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
TgeneIL22RA1chr17:78237577chr1:24465204ENST0000027080007141_22114.333333333333334575.0DomainFibronectin type-III 2
TgeneIL22RA1chr17:78237577chr1:24465204ENST000002708000717_12414.333333333333334575.0DomainFibronectin type-III 1
TgeneIL22RA1chr17:78237577chr1:24465204ENST000002708000716_22814.333333333333334575.0Topological domainExtracellular
TgeneIL22RA1chr17:78237577chr1:24465204ENST0000027080007250_57414.333333333333334575.0Topological domainCytoplasmic
TgeneIL22RA1chr17:78237577chr1:24465204ENST0000027080007229_24914.333333333333334575.0TransmembraneHelical

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneRNF213chr17:78237577chr1:24465204ENST00000319921+217343_37432.3333333333333361064.0Coiled coilOntology_term=ECO:0000255
HgeneRNF213chr17:78237577chr1:24465204ENST00000508628+269343_37432.3333333333333365257.0Coiled coilOntology_term=ECO:0000255
HgeneRNF213chr17:78237577chr1:24465204ENST00000582970+268343_37432.3333333333333365208.0Coiled coilOntology_term=ECO:0000255
HgeneRNF213chr17:78237577chr1:24465204ENST00000319921+2173997_403632.3333333333333361064.0Zinc fingerRING-type
HgeneRNF213chr17:78237577chr1:24465204ENST00000508628+2693997_403632.3333333333333365257.0Zinc fingerRING-type
HgeneRNF213chr17:78237577chr1:24465204ENST00000582970+2683997_403632.3333333333333365208.0Zinc fingerRING-type


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Fusion Protein Structures

check button PDB and CIF files of the predicted fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
Fusion protein PDB link (fusion AA seq ID in FusionPDB)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file >>>1259_RNF213_78237577_IL22RA1_24465204_1259_RNF213_78237577_IL22RA1_24465204_ranked_0.pdbRNF2137823757778237577ENST00000270800IL22RA1chr124465204-
MECPSCQHVSKEETPKFCSQCGERLPPAAPIAAHAPEDPSDLLQHVKFQSSNFENILTWDSGPEGTPDTVYSIEYKTYGERDWVAKKGCQ
RITRKSCNLTVETGNLTELYYARVTAVSAGGRSATKMTDRFSSLQHTTLKPPDVTCISKVRSIQMIVHPTPTPIRAGDGHRLTLEDIFHD
LFYHLELQVNRTYQMHLGGKQREYEFFGLTPDTEFLGTIMICVPTWAKESAPYMCRVKTLPDRTWTYSFSGAFLFSMGFLVAVLCYLSYR
YVTKPPAPPNSLNVQRVLTFQPLRFIQEHVLIPVFDLSGPSSLAQPVQYSQIRVSGPREPAGAPQRHSLSEITYLGQPDISILQPSNVPP
PQILSPLSYAPNAAPEVGPPSYAPQVTPEAQFPFYAPQAISKVQPSSYAPQATPDSWPPSYGVCMEGSGKDSPTGTLSSPKHLRPKGQLQ
KEPPAGSCMLGGLSLQEVTSLAMEESQEAKSLHQPLGICTDRTSDPNVLHSGEEGTPQYLKGQLPLLSSVQIEGHPMSLPLQPPSRPCSP
592


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pLDDT score distribution

check button pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
RNF213_pLDDT.png
all structure
all structure
IL22RA1_pLDDT.png
all structure
all structure

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
all structure


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Ramachandran Plot of Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.
Fusion AA seq ID in FusionPDB and their Ramachandran plots

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Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)
GenePPI interactors
RNF213tat, UBC, vpu, CBX2, CBX4, CBX6, EGFR, PLAC9, RNF213, TRIM23, GOLGA2, REL, TRIM27, TRIP6, UBXN11, KRT40, CD244, SCN2B, IFI16, PTPN1, MRPL50, RNASEH2B, Kif4, Ube2k, Rpl35, GAN, MCM2, ATOH1, DLK2, SIGLECL1, SDC2, LAMP3, CYLD, HNRNPL, UBE2M, USP15, LYAR, HNRNPK, ITPR3, UBE2L3, UBE2D2, ESR2, RNF123, KIAA1429, CTDP1, MTDH, CEBPD, UNC93B1, AHNAK2, COPE, CPNE8, GNB1, GTSE1, LMNA, NOLC1, PLOD2, RPS12, SCRIB, SMTN, SNRPD2, SRPR, TCEB2, TPM2, UACA, ORF7a, SH2D3C, HIST1H1A, nsp5, nsp2, nsp6, CIT, AURKB, CHMP4C, KIF14, TRIM66, FIS1, OCIAD1, SUMO2, BRD4, CUL4A, UBE2D3, BAG5, AR, ATG5, IGHM, SLC35G1, NPTN, OPALIN, EFNB1, GCGR, C19orf38, HCST, LOC388882, GPR17, C5AR1, UPK2, CD40, OSTM1, FPR1, TACSTD2, RELT, TMEM55B, VSIG4, HLA-B, TMEM9B, NPDC1, BSG, GPR45, FAM174A, STK16, GPR182, MFSD4, MGARP, CLEC4A, HS2ST1, FFAR1, SGCA, HLA-C, UBE2N, UBE2U, SLFN11, FBXW7,


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
RNF213
IL22RA1


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to RNF213-IL22RA1


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 RNF213-IL22RA1


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
HgeneRNF213C1846689MOYAMOYA DISEASE 29CTD_human;UNIPROT
HgeneRNF213C0026654Moyamoya Disease3ORPHANET
HgeneRNF213C2931384Moyamoya disease 13ORPHANET