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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:CDKL5-DHFR (FusionGDB2 ID:HG6792TG1719)

Fusion Gene Summary for CDKL5-DHFR

check button Fusion gene summary
Fusion gene informationFusion gene name: CDKL5-DHFR
Fusion gene ID: hg6792tg1719
HgeneTgene
Gene symbol

CDKL5

DHFR

Gene ID

6792

1719

Gene namecyclin dependent kinase like 5dihydrofolate reductase
SynonymsCFAP247|EIEE2|ISSX|STK9DHFRP1|DYR
Cytomap('CDKL5')('DHFR')

Xp22.13

5q14.1

Type of geneprotein-codingprotein-coding
Descriptioncyclin-dependent kinase-like 5cyclin dependent kinase 5 transcriptserine/threonine kinase 9serine/threonine-protein kinase 9dihydrofolate reductase
Modification date2020031520200315
UniProtAcc.

P00374

Ensembl transtripts involved in fusion geneENST00000379989, ENST00000379996, 
ENST00000463994, 
Fusion gene scores* DoF score7 X 6 X 3=1269 X 9 X 2=162
# samples 89
** MAII scorelog2(8/126*10)=-0.655351828612554
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(9/162*10)=-0.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: CDKL5 [Title/Abstract] AND DHFR [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointCDKL5(18617570)-DHFR(79946459), # samples:1
Anticipated loss of major functional domain due to fusion event.
* 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
HgeneCDKL5

GO:0046777

protein autophosphorylation

16935860

HgeneCDKL5

GO:0099175

regulation of postsynapse organization

22922712

TgeneDHFR

GO:0017148

negative regulation of translation

8490020

TgeneDHFR

GO:0046452

dihydrofolate metabolic process

2303423|23707606

TgeneDHFR

GO:0046653

tetrahydrofolate metabolic process

12096917|21876184

TgeneDHFR

GO:0046654

tetrahydrofolate biosynthetic process

2303423

TgeneDHFR

GO:0055114

oxidation-reduction process

23707606



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
ChiTaRS5.0N/AEC493836CDKL5chrX

18617570

-DHFRchr5

79946459

-


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Fusion Gene ORF analysis for CDKL5-DHFR

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
intron-intronENST00000379989ENST00000439211CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000379989ENST00000504396CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000379989ENST00000505337CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000379989ENST00000511032CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000379989ENST00000513048CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000379996ENST00000439211CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000379996ENST00000504396CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000379996ENST00000505337CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000379996ENST00000511032CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000379996ENST00000513048CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000463994ENST00000439211CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000463994ENST00000504396CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000463994ENST00000505337CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000463994ENST00000511032CDKL5chrX

18617570

-DHFRchr5

79946459

-
intron-intronENST00000463994ENST00000513048CDKL5chrX

18617570

-DHFRchr5

79946459

-

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

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

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Fusion Genomic Features for CDKL5-DHFR


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)


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Fusion Protein Features for CDKL5-DHFR


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/:18617570/:79946459)
- 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
.DHFR

P00374

FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.FUNCTION: Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2. {ECO:0000269|PubMed:12096917, ECO:0000269|PubMed:21876188}.

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.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for CDKL5-DHFR


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for CDKL5-DHFR


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 (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for CDKL5-DHFR


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status
TgeneDHFRP00374DB00563MethotrexateInhibitorSmall moleculeApproved
TgeneDHFRP00374DB01131ProguanilInhibitorSmall moleculeApproved
TgeneDHFRP00374DB00642PemetrexedInhibitorSmall moleculeApproved|Investigational
TgeneDHFRP00374DB01157TrimetrexateInhibitorSmall moleculeApproved|Investigational
TgeneDHFRP00374DB06813PralatrexateInhibitorSmall moleculeApproved|Investigational
TgeneDHFRP00374DB00205PyrimethamineInhibitorSmall moleculeApproved|Investigational|Vet_approved
TgeneDHFRP00374DB00157NADHSmall moleculeApproved|Nutraceutical
TgeneDHFRP00374DB00798GentamicinSmall moleculeApproved|Vet_approved

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Related Diseases for CDKL5-DHFR


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneCDKL5C1839333EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 223CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
HgeneCDKL5C0037769West Syndrome2ORPHANET
HgeneCDKL5C0014544Epilepsy1CTD_human
HgeneCDKL5C0022333Jacksonian Seizure1CTD_human
HgeneCDKL5C0035372Rett Syndrome1CTD_human
HgeneCDKL5C0036572Seizures1CTD_human
HgeneCDKL5C0086237Epilepsy, Cryptogenic1CTD_human
HgeneCDKL5C0149958Complex partial seizures1CTD_human
HgeneCDKL5C0162635Angelman Syndrome1CTD_human;GENOMICS_ENGLAND
HgeneCDKL5C0234533Generalized seizures1CTD_human
HgeneCDKL5C0234535Clonic Seizures1CTD_human
HgeneCDKL5C0236018Aura1CTD_human
HgeneCDKL5C0270824Visual seizure1CTD_human
HgeneCDKL5C0270844Tonic Seizures1CTD_human
HgeneCDKL5C0270846Epileptic drop attack1CTD_human
HgeneCDKL5C0393706Early infantile epileptic encephalopathy with suppression bursts1ORPHANET
HgeneCDKL5C0422850Seizures, Somatosensory1CTD_human
HgeneCDKL5C0422852Seizures, Auditory1CTD_human
HgeneCDKL5C0422853Olfactory seizure1CTD_human
HgeneCDKL5C0422854Gustatory seizure1CTD_human
HgeneCDKL5C0422855Vertiginous seizure1CTD_human
HgeneCDKL5C0494475Tonic - clonic seizures1CTD_human
HgeneCDKL5C0751056Non-epileptic convulsion1CTD_human
HgeneCDKL5C0751110Single Seizure1CTD_human
HgeneCDKL5C0751111Awakening Epilepsy1CTD_human
HgeneCDKL5C0751123Atonic Absence Seizures1CTD_human
HgeneCDKL5C0751494Convulsive Seizures1CTD_human
HgeneCDKL5C0751495Seizures, Focal1CTD_human
HgeneCDKL5C0751496Seizures, Sensory1CTD_human
HgeneCDKL5C1535926Neurodevelopmental Disorders1CTD_human
HgeneCDKL5C2748910Rett Syndrome, Atypical1ORPHANET
HgeneCDKL5C3495874Nonepileptic Seizures1CTD_human
HgeneCDKL5C4048158Convulsions1CTD_human
HgeneCDKL5C4316903Absence Seizures1CTD_human
HgeneCDKL5C4317109Epileptic Seizures1CTD_human
HgeneCDKL5C4317123Myoclonic Seizures1CTD_human
HgeneCDKL5C4505436Generalized Absence Seizures1CTD_human
TgeneC3151205Megaloblastic Anemia due to Dihydrofolate Reductase Deficiency4CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneC0002888Anemia, Megaloblastic2CTD_human
TgeneC0006142Malignant neoplasm of breast2CTD_human
TgeneC0025521Inborn Errors of Metabolism2CTD_human
TgeneC0027765nervous system disorder2CTD_human
TgeneC0268608Deficiency of dihydrofolate reductase2GENOMICS_ENGLAND
TgeneC0678222Breast Carcinoma2CTD_human
TgeneC1257931Mammary Neoplasms, Human2CTD_human
TgeneC1458155Mammary Neoplasms2CTD_human
TgeneC4704874Mammary Carcinoma, Human2CTD_human
TgeneC0000786Spontaneous abortion1CTD_human
TgeneC0000822Abortion, Tubal1CTD_human
TgeneC0003873Rheumatoid Arthritis1CTD_human
TgeneC0004352Autistic Disorder1CTD_human
TgeneC0009402Colorectal Carcinoma1CTD_human
TgeneC0009404Colorectal Neoplasms1CTD_human
TgeneC0013221Drug toxicity1CTD_human
TgeneC0016412Folic Acid Deficiency1CTD_human
TgeneC0019193Hepatitis, Toxic1CTD_human
TgeneC0021361Female infertility1CTD_human
TgeneC0027627Neoplasm Metastasis1CTD_human
TgeneC0029463Osteosarcoma1CTD_human
TgeneC0030312Pancytopenia1CTD_human
TgeneC0038279Sterility, Postpartum1CTD_human
TgeneC0041755Adverse reaction to drug1CTD_human
TgeneC0341869Subfertility, Female1CTD_human
TgeneC0860207Drug-Induced Liver Disease1CTD_human
TgeneC0917730Female sterility1CTD_human
TgeneC1262760Hepatitis, Drug-Induced1CTD_human
TgeneC3658290Drug-Induced Acute Liver Injury1CTD_human
TgeneC3830362Early Pregnancy Loss1CTD_human
TgeneC4277682Chemical and Drug Induced Liver Injury1CTD_human
TgeneC4279912Chemically-Induced Liver Toxicity1CTD_human
TgeneC4552766Miscarriage1CTD_human