Target Information

Target General Information

Target ID

T26470

Target Name

B-cell lymphoma/leukemia 11A (BCL11A)

Synonyms

BCL-11A; B-cell CLL/lymphoma 11A; COUP-TF-interacting protein 1; Ecotropic viral integration site 9 protein homolog; EVI-9; Zinc finger protein 856; BCL-11A; B-cell CLL/lymphoma 11A; COUP-TF-interacting protein 1; Ecotropic viral integration site 9 protein homolog; EVI-9; Zinc finger protein 856

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Gene Name

BCL11A

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Sickle-cell disorder [ICD-11: 3A51]

Thalassaemia [ICD-11: 3A50]

Function

Transcription factor associated with the BAF SWI/SNF chromatin remodeling complex (By similarity). Repressor of fetal hemoglobin (HbF) level. Involved in brain development. May play a role in hematopoiesis. Essential factor in lymphopoiesis required for B-cell formation in fetal liver. May function as a modulator of the transcriptional repression activity of ARP1 (By similarity).

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UniProt ID

BC11A_HUMAN

Sequence

MSRRKQGKPQHLSKREFSPEPLEAILTDDEPDHGPLGAPEGDHDLLTCGQCQMNFPLGDI
LIFIEHKRKQCNGSLCLEKAVDKPPSPSPIEMKKASNPVEVGIQVTPEDDDCLSTSSRGI
CPKQEHIADKLLHWRGLSSPRSAHGALIPTPGMSAEYAPQGICKDEPSSYTCTTCKQPFT
SAWFLLQHAQNTHGLRIYLESEHGSPLTPRVGIPSGLGAECPSQPPLHGIHIADNNPFNL
LRIPGSVSREASGLAEGRFPPTPPLFSPPPRHHLDPHRIERLGAEEMALATHHPSAFDRV
LRLNPMAMEPPAMDFSRRLRELAGNTSSPPLSPGRPSPMQRLLQPFQPGSKPPFLATPPL
PPLQSAPPPSQPPVKSKSCEFCGKTFKFQSNLVVHRRSHTGEKPYKCNLCDHACTQASKL
KRHMKTHMHKSSPMTVKSDDGLSTASSPEPGTSDLVGSASSALKSVVAKFKSENDPNLIP
ENGDEEEEEDDEEEEEEEEEEEEELTESERVDYGFGLSLEAARHHENSSRGAVVGVGDES
RALPDVMQGMVLSSMQHFSEAFHQVLGEKHKRGHLAEAEGHRDTCDEDSVAGESDRIDDG
TVNGRGCSPGESASGGLSKKLLLGSPSSLSPFSKRIKLEKEFDLPPAAMPNTENVYSQWL
AGYAASRQLKDPFLSFGDSRQSPFASSSEHSSENGSLRFSTPPGELDGGISGRSGTGSGG
STPHISGPGPGRPSSKEGRRSDTCEYCGKVFKNCSNLTVHRRSHTGERPYKCELCNYACA
QSSKLTRHMKTHGQVGKDVYKCEICKMPFSVYSTLEKHMKKWHSDRVLNNDIKTE

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3D Structure

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AlphaFold

HIT2.0 ID

T54BUS

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

CTX001

Drug Info

Phase 1/2

Sickle-cell disorder

[2]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
RE1-silencing transcription factor (REST)	PF13909	40.698 (35/86)	1.31E-13
Zinc finger protein Pegasus (IKZF5)		40.000 (32/80)	3.15E-11

Degree	2	Degree centrality	2.15E-04	Betweenness centrality	0.00E+00
Closeness centrality	1.91E-01	Radiality	1.33E+01	Clustering coefficient	1.00E+00
Neighborhood connectivity	4.20E+01	Topological coefficient	5.32E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

Off-the-shelf' allogeneic CAR T cells: development and challenges. Nat Rev Drug Discov. 2020 Mar;19(3):185-199.

REF 2

ClinicalTrials.gov (NCT03745287) A Safety and Efficacy Study Evaluating CTX001 in Subjects With Severe Sickle Cell Disease. U.S. National Institutes of Health.

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