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	Kinase Fusion Gene Summary
	Kinase Fusion Gene Sample Information
	Kinase Fusion ORF Analysis
	Kinase Fusion Amino Acid Sequences
	Multiple Sequence Alignment of All Fusion Protein Isoforms
	Kinase Fusion Protein Functional Features
	Kinase Fusion Protein Structures
	Comparison of Fusion Protein Isoforms
	Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB
	pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.
	Ramachandran Plot of Kinase Fusion Protein Structure
	Potential Active Site Information
	Virtual Screening Results
	Kinase-Substrate Information
	Related Drugs with This Kinase Fusion Protein
	Related Disease with This Kinase Fusion Protein
	Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:ADRBK2_AP1B1

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: ADRBK2_AP1B1
	KinaseFusionDB ID: KFG201
	FusionGDB2.0 ID: KFG201
		Hgene	Tgene
	Gene symbol	ADRBK2	AP1B1
	Gene ID	157	162
	Gene name	G protein-coupled receptor kinase 3	adaptor related protein complex 1 subunit beta 1
	Synonyms	ADRBK2\|BARK2	ADTB1\|AP105A\|BAM22\|CLAPB2\|KIDAR
	Cytomap	22q12.1	22q12.2
	Type of gene	protein-coding	protein-coding
	Description	G protein-coupled receptor kinase 3beta-adrenergic receptor kinase 2adrenergic, beta, receptor kinase 2beta-ARK-2	AP-1 complex subunit beta-1ADTB1, CLAPB2Golgi adaptor HA1/AP1 adaptin beta subunitadapter-related protein complex 1 subunit beta-1adaptor protein complex AP-1 subunit beta-1adaptor related protein complex 1 beta 1 subunitbeta-1-adaptinbeta-adaptin
	Modification date	20240403	20240305
	UniProtAcc	P35626	Q10567
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000324198,	ENST00000472057, ENST00000317368, ENST00000356015, ENST00000357586, ENST00000402502, ENST00000405198, ENST00000415447, ENST00000432560,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: ADRBK2 [Title/Abstract] AND AP1B1 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	AP1B1(29750639)-ADRBK2(26091074), # samples:2 ADRBK2(26086250)-AP1B1(29747814), # samples:2

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Hgene	ADRBK2	GO:0031623	receptor internalization	20074556

Kinase Fusion gene breakpoints across ADRBK2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Kinase Fusion gene breakpoints across AP1B1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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Kinase Fusion Gene Sample Information

Kinase Fusion gene information.

Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE)
* 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.

Source	Sample	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp
ChimerDB4	TCGA-C4-A0F7-01A	ADRBK2	chr22	26086250	AP1B1	chr22	29747814

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Kinase Fusion ORF Analysis

Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.

Henst	Tenst	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	Seq length (transcript)	Seq length (amino acids)
ENST00000324198	ENST00000356015	ADRBK2	chr22	26086250	AP1B1	chr22	29747814	4274	980

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Kinase Fusion Amino Acid Sequences

For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq

>ENST00000324198_ENST00000356015_ADRBK2_chr22_26086250_AP1B1_chr22_29747814_length(amino acids)=980
MADLEAVLADVSYLMAMEKSKATPAARASKRIVLPEPSIRSVMQKYLAERNEITFDKIFNQKIGFLLFKDFCLNEINEAVPQVKFYEEIK
EYEKLDNEEDRLCRSRQIYDAYIMKELLSCSHPFSKQAVEHVQSHLSKKQVTSTLFQPYIEEICESLRGDIFQKFMESDKFTRFCQWKNV
ELNIHLTMNEFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQGETLALNERIMLSLVSTGDCPFIVCMTYAFHTPDKLCFI
LDLMNGGDLHYHLSQHGVFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILLDEHGHARISDLGLACDFSKKKPHASVPEILKHEMK
VFFVKYNDPIYVKLEKLDIMIRLASQANIAQVLAELKEYATEVDVDFVRKAVRAIGRCAIKVEQSAERCVSTLLDLIQTKVNYVVQEAIV
VIKDIFRKYPNKYESVIATLCENLDSLDEPEARAAMIWIVGEYAERIDNADELLESFLEGFHDESTQVQLQLLTAIVKLFLKKPTETQEL
VQQVLSLATQDSDNPDLRDRGYIYWRLLSTDPVAAKEVVLAEKPLISEETDLIEPTLLDELICYIGTLASVYHKPPSAFVEGGRGVVHKS
LPPRTASSESAESPETAPTGAPPGEQPDVIPAQGDLLGDLLNLDLGPPVSGPPLATSSVQMGAVDLLGGGLDSLIGGTNFVAPPTAAVPA
NLGAPIGSGLSDLFDLTSGVGTLSGSYVAPKAVWLPAMKAKGLEISGTFTRQVGSISMDLQLTNKALQVMTDFAIQFNRNSFGLAPATPL
QVHAPLSPNQTVEISLPLSTVGSVMKMEPLNNLQVAVKNNIDVFYFSTLYPLHILFVEDGKMDRQMFLATWKDIPNENEAQFQIRDCPLN

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr22:29750639/chr22:26091074)
- 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.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
ADRBK2 P35626	AP1B1 Q10567
FUNCTION: Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors. {ECO:0000250\|UniProtKB:P26819}.	FUNCTION: Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes (PubMed:31630791). The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. {ECO:0000269\|PubMed:31630791}.

Retention 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 domain in the 5'-partner of fusion protein (protein functional feature from UniProt).

350

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

Hgene

ADRBK2

26086250

AP1B1

29747814

ENST00000324198

54_175

689

Domain

Note=RGS;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00171

- Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

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Kinase Fusion Protein Structures

CIF files of the predicted kinase 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.

Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB)	Henst	Tenst	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	AA seq	Len(AA seq)
PDB file >>>20_ADRBK2_AP1B1	ENST00000324198	ENST00000356015	ADRBK2	chr22	26086250	AP1B1	chr22	29747814	MADLEAVLADVSYLMAMEKSKATPAARASKRIVLPEPSIRSVMQKYLAERNEITFDKIFNQKIGFLLFKDFCLNEINEAVPQVKFYEEIK EYEKLDNEEDRLCRSRQIYDAYIMKELLSCSHPFSKQAVEHVQSHLSKKQVTSTLFQPYIEEICESLRGDIFQKFMESDKFTRFCQWKNV ELNIHLTMNEFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQGETLALNERIMLSLVSTGDCPFIVCMTYAFHTPDKLCFI LDLMNGGDLHYHLSQHGVFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILLDEHGHARISDLGLACDFSKKKPHASVPEILKHEMK VFFVKYNDPIYVKLEKLDIMIRLASQANIAQVLAELKEYATEVDVDFVRKAVRAIGRCAIKVEQSAERCVSTLLDLIQTKVNYVVQEAIV VIKDIFRKYPNKYESVIATLCENLDSLDEPEARAAMIWIVGEYAERIDNADELLESFLEGFHDESTQVQLQLLTAIVKLFLKKPTETQEL VQQVLSLATQDSDNPDLRDRGYIYWRLLSTDPVAAKEVVLAEKPLISEETDLIEPTLLDELICYIGTLASVYHKPPSAFVEGGRGVVHKS LPPRTASSESAESPETAPTGAPPGEQPDVIPAQGDLLGDLLNLDLGPPVSGPPLATSSVQMGAVDLLGGGLDSLIGGTNFVAPPTAAVPA NLGAPIGSGLSDLFDLTSGVGTLSGSYVAPKAVWLPAMKAKGLEISGTFTRQVGSISMDLQLTNKALQVMTDFAIQFNRNSFGLAPATPL QVHAPLSPNQTVEISLPLSTVGSVMKMEPLNNLQVAVKNNIDVFYFSTLYPLHILFVEDGKMDRQMFLATWKDIPNENEAQFQIRDCPLN	980
3D view using mol* of 20_ADRBK2_AP1B1

PDB file >>>HKFP_23_ADRBK2_AP1B1	ENST00000324198	ENST00000356015	ADRBK2	chr22	26086250	AP1B1	chr22	29747814	MADLEAVLADVSYLMAMEKSKATPAARASKRIVLPEPSIRSVMQKYLAERNEITFDKIFNQKIGFLLFKDFCLNEINEAVPQVKFYEEIK EYEKLDNEEDRLCRSRQIYDAYIMKELLSCSHPFSKQAVEHVQSHLSKKQVTSTLFQPYIEEICESLRGDIFQKFMESDKFTRFCQWKNV ELNIHLTMNEFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQGETLALNERIMLSLVSTGDCPFIVCMTYAFHTPDKLCFI LDLMNGGDLHYHLSQHGVFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILLDEHGHARISDLGLACDFSKKKPHASVPEILKHEMK VFFVKYNDPIYVKLEKLDIMIRLASQANIAQVLAELKEYATEVDVDFVRKAVRAIGRCAIKVEQSAERCVSTLLDLIQTKVNYVVQEAIV VIKDIFRKYPNKYESVIATLCENLDSLDEPEARAAMIWIVGEYAERIDNADELLESFLEGFHDESTQVQLQLLTAIVKLFLKKPTETQEL VQQVLSLATQDSDNPDLRDRGYIYWRLLSTDPVAAKEVVLAEKPLISEETDLIEPTLLDELICYIGTLASVYHKPPSAFVEGGRGVVHKS LPPRTASSESAESPETAPTGAPPGEQPDVIPAQGDLLGDLLNLDLGPPVSGPPLATSSVQMGAVDLLGGGLDSLIGGTNFVAPPTAAVPA NLGAPIGSGLSDLFDLTSGVGTLSGSYVAPKAVWLPAMKAKGLEISGTFTRQVGSISMDLQLTNKALQVMTDFAIQFNRNSFGLAPATPL QVHAPLSPNQTVEISLPLSTVGSVMKMEPLNNLQVAVKNNIDVFYFSTLYPLHILFVEDGKMDRQMFLATWKDIPNENEAQFQIRDCPLN	980_ADRBK2_AP1B1

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Comparison of Fusion Protein Isoforms

Superimpose the 3D Structures Among All Fusion Protein Isoforms
* Download the pdb file and open it from the molstar online viewer.

Comparison of the Secondary Structures of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

ADRBK2_AP1B1 does not have any known PDB structures.

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pLDDT score distribution

pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
* The blue color at the bottom marks the best active site residues.

20_ADRBK2_AP1B1.png

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Potential Active Site Information

The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.

Kinase Fusion AA seq ID in KinaseFusionDB

Site score

Size

Dscore

Volume

Exposure

Enclosure

Contact

Phobic

Philic

Balance

Don/Acc

Residues

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Ramachandran Plot of Kinase Fusion Protein Structure

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.

20_ADRBK2_AP1B1_ramachandran.png

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Virtual Screening Results

Distribution of the average docking score across all approved kinase inhibitors.
Distribution of the number of occurrence across all approved kinase inhibitors.

5'-kinase fusion protein case

3'-kinase fusion protein case

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Drug information from DrugBank of the top 20 interacting small molecules.
* The detailed information of individual kinase inhibitors are available in the download page.

Fusion gene name info	Drug	Docking score	Glide g score	Glide energy
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Lapatinib	-7.30369	-7.39249	-58.3079
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Lapatinib	-7.224480000000001	-7.313280000000001	-57.1599
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Entrectinib	-7.20107	-7.26577	-44.0134
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Entrectinib	-7.20107	-7.26577	-44.0134
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Entrectinib	-6.99615	-7.06085	-42.9012
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Netarsudil	-6.978739999999999	-6.989839999999999	-45.7655
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Netarsudil	-6.978739999999999	-6.989839999999999	-45.7655
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Neratinib	-6.90292	-7.08882	-52.376999999999995
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Neratinib	-6.664739999999999	-6.84704	-50.4813
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Neratinib	-6.664739999999999	-6.84704	-50.4813
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Asciminib	-6.44286	-6.90786	-38.4997
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Pralsetinib	-6.37427	-6.46577	-47.4404
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Fedratinib	-6.3221	-6.3735	-53.1049
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Fedratinib	-6.3221	-6.3735	-53.1049
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Cobimetinib	-6.28313	-6.2859300000000005	-35.9157
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Lapatinib	-6.28212	-7.45052	-58.6367
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Lapatinib	-6.28212	-7.45052	-58.6367
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Pexidartinib	-6.24084	-6.4576400000000005	-39.3164
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Pexidartinib	-6.24084	-6.4576400000000005	-39.3164
20_ADRBK2_AP1B1-DOCK_HTVS_1-001	Pralsetinib	-6.23621	-6.32771	-46.6843

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Kinase-Substrate Information of ADRBK2_AP1B1

Phosphorylation target of the kinase
(phosphosite, 03-17-2024)

Kinase

Kinase UniProt Acc

Kinase species

Substrate

Substrate UniProt Acc

Substrate phosphorylated residues

Substrate phosphorylated sites (+/-7AA)

Domain

Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

Enriched GO biological processes of the phosphorylation target genes of the kinase

Kinase

GOID

GO term

P.adjust

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Related Drugs to ADRBK2_AP1B1

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

Hgene

Tgene

Drug

Source

PMID

Distribution of the number of studies mentioning ADRBK2-AP1B1 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1

Fusion gene - drug pair 2

PMID

Publication date

DOI

Study title

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Related Diseases to ADRBK2_AP1B1

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

Hgene

Tgene

Disease

Source

PMID

Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)

MeSH ID

MeSH term

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source

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Clinical Trials of the Found Drugs/Small Molecules

Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion Gene

Kinase Inhibitor

NCT ID

Study Status

Phases

Disease

# Enrolment

Date