BCL11A

Summary

BCL11A (BCL11 transcription factor A, HGNC:13221) is a protein-coding gene on chromosome 2p16.1, encoding BCL11 transcription factor A (Q9H165). Transcription factor. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a C2H2 type zinc-finger protein by its similarity to the mouse Bcl11a/Evi9 protein. The corresponding mouse gene is a common site of retroviral integration in myeloid leukemia, and may function as a leukemia disease gene, in part, through its interaction with BCL6. During hematopoietic cell differentiation, this gene is down-regulated. It is possibly involved in lymphoma pathogenesis since translocations associated with B-cell malignancies also deregulates its expression. Multiple transcript variants encoding several different isoforms have been found for this gene.

Source: NCBI Gene 53335 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Dias-Logan syndrome (Definitive, ClinGen)
• GWAS associations: 111
• Clinical variants (ClinVar): 342 total — 53 pathogenic, 40 likely-pathogenic
• Phenotypes (HPO): 44
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 16 downstream targets (CollecTRI)
• MANE Select transcript: NM_022893

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13221
Approved symbol	BCL11A
Name	BCL11 transcription factor A
Location	2p16.1
Locus type	gene with protein product
Status	Approved
Aliases	BCL11A-XL, BCL11A-L, BCL11A-S, CTIP1, HBFQTL5, ZNF856, SMARCM1
Ensembl gene	ENSG00000119866
Ensembl biotype	protein_coding
OMIM	606557
Entrez	53335

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 17 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000335712, ENST00000356842, ENST00000358510, ENST00000359629, ENST00000409351, ENST00000477659, ENST00000479026, ENST00000489183, ENST00000489516, ENST00000492272, ENST00000631857, ENST00000642180, ENST00000642384, ENST00000642439, ENST00000642824, ENST00000643004, ENST00000643222, ENST00000643459, ENST00000643716, ENST00000644606, ENST00000645224, ENST00000645405, ENST00000645455, ENST00000646249, ENST00000647038, ENST00000647469, ENST00000647472

RefSeq mRNA: 33 — MANE Select: NM_022893 NM_001363864, NM_001365609, NM_001405708, NM_001405709, NM_001405710, NM_001405711, NM_001405712, NM_001405713, NM_001405714, NM_001405715, NM_001405716, NM_001405718, NM_001405719, NM_001405720, NM_001405721, NM_001405722, NM_001405723, NM_001405724, NM_001405725, NM_001405726, NM_001405727, NM_001405728, NM_001405729, NM_001405730, NM_001405731, NM_001405732, NM_001405733, NM_001405734, NM_001405735, NM_001405736, NM_018014, NM_022893, NM_138559

CCDS: CCDS1861, CCDS1862, CCDS46295, CCDS86845, CCDS92761

Canonical transcript exons

ENST00000642384 — 4 exons

Exon	Start	End
ENSE00001355365	60457194	60462424
ENSE00003686382	60468732	60468833
ENSE00003690078	60545971	60546300
ENSE00003820610	60553216	60553654

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 99.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.7191 / max 6215.1150, expressed in 1251 samples.

FANTOM5 promoters (26 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28605	10.6481	885
28607	9.9310	1078
28612	2.1456	265
28596	1.6050	487
28606	0.3483	159
28597	0.3112	162
28604	0.2404	95
28588	0.2352	102
28579	0.2227	107
28603	0.2205	80

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.39	gold quality
ganglionic eminence	UBERON:0004023	98.64	gold quality
primary visual cortex	UBERON:0002436	96.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.58	gold quality
skin of hip	UBERON:0001554	96.28	gold quality
upper leg skin	UBERON:0004262	96.02	gold quality
middle temporal gyrus	UBERON:0002771	95.86	gold quality
postcentral gyrus	UBERON:0002581	95.44	gold quality
CA1 field of hippocampus	UBERON:0003881	95.10	gold quality
occipital lobe	UBERON:0002021	94.95	gold quality
ventricular zone	UBERON:0003053	94.71	gold quality
parietal lobe	UBERON:0001872	94.42	gold quality
superior frontal gyrus	UBERON:0002661	94.30	gold quality
tonsil	UBERON:0002372	94.25	gold quality
orbitofrontal cortex	UBERON:0004167	94.18	gold quality
entorhinal cortex	UBERON:0002728	94.00	gold quality
oral cavity	UBERON:0000167	93.99	gold quality
prefrontal cortex	UBERON:0000451	93.89	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.74	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.55	gold quality
buccal mucosa cell	CL:0002336	93.37	gold quality
epithelium of nasopharynx	UBERON:0001951	93.29	gold quality
endothelial cell	CL:0000115	93.28	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.24	gold quality
cerebral cortex	UBERON:0000956	93.10	gold quality
neocortex	UBERON:0001950	93.04	gold quality
cervix squamous epithelium	UBERON:0006922	93.04	gold quality
frontal cortex	UBERON:0001870	92.95	gold quality
putamen	UBERON:0001874	92.83	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	5533.09
E-MTAB-8498	yes	3879.49
E-GEOD-76312	yes	3157.87
E-MTAB-6678	yes	1389.67
E-MTAB-6505	yes	956.15
E-GEOD-93593	yes	944.27
E-HCAD-5	yes	900.85
E-MTAB-10485	yes	793.21
E-HCAD-32	yes	538.54
E-MTAB-10553	yes	532.60
E-MTAB-3929	yes	143.87
E-HCAD-4	yes	108.09
E-CURD-112	yes	43.96
E-HCAD-1	yes	20.39
E-MTAB-6701	yes	20.33

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

16 targets.

Target	Regulation
CD34
CDKN2A
DCC	Activation
FRZB	Activation
GATA1	Activation
H3C1
HBB	Repression
HBD
HBE1	Repression
HBG1	Repression
HBG2	Repression
HBZ	Repression
ID3	Activation
MAP1B	Activation
SIRT1
TCF4	Activation

JASPAR motifs

Motif	Name	Family
MA2324.1	BCL11A	Factors with multiple dispersed zinc fingers
MA2504.1	BCL11A	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:29606353, PMID:29610478

Upstream regulators (CollecTRI, top): CHD4, E2F4, FOXQ1, KLF1, SIRT1

miRNA regulators (miRDB)

333 targeting BCL11A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-32-5P	99.98	75.21	1964

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• BCL11A may not be the target of the 2p13 alterations in cHL(clasical Hodgkins lymphoma),rather REL is. (PMID:11830502)
• The t(2;14)(p13;q32.3) involving the BCL11A and IGH genes is associated with a subset of B-CLL/immunocytoma characterized by non-mutated IG genes deriving from pre-germinal center B cells. (PMID:11986957)
• SIRT1 has a role in transcriptional repression mediated by BCL11A in mammalian cells (PMID:15639232)
• The most abundant isoform BCL11A-XL was DNA-sequence-specific transcriptional repressor that associates with itself and with other BCL11A isoforms, as well as with the BCL6 proto-oncogene. (PMID:16704730)
• essential functional role of this repressor of transcription in primary mediastinal B-cell lymphoma (PMID:16871282)
• the apparent occurrence of an unusual TG 3’ splice site in intron 4 is discussed (PMID:17672918)
• These results indicate that BCL11A variants, by modulating HbF levels, act as an important ameliorating factor of the beta-thalassemia phenotype, and it is likely they could help ameliorate other hemoglobin disorders. (PMID:18245381)
• BCL11A is a SUMOylated protein and recruits SUMO-conjugation enzymes in its nuclear body. (PMID:18681895)
• Study shows that SNPs in BCL11A were associated with HbF containing erythrocyte numbers in Chinese with beta-thalassemia trait, and with HbF levels in Thais with either beta-thalassemia or HbE trait and in African Americans with sickle cell anemia. (PMID:18691915)
• deregulated Bcl11a cooperates with Nf1 in leukemogenesis (PMID:18948576)
• down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression; study finds that BCL11A occupies several discrete sites in the beta-globin gene cluster (PMID:19056937)
• BCL11A binds a core motif in the gamma-globin proximal promoter, recruits and interacts with partners to form a repression complex, leading to deacetylation of histones and down-regulation of gamma-globin transcription. (PMID:19153051)
• Chronic lymphocytic leukemia With t(2;14)(p16;q32) involves the BCL11A and IgH genes and is associated with atypical morphologic features and unmutated IgVH genes. (PMID:19369625)
• Data report that Bcl11A downregulates axon branching, and that the expression of DCC and MAP1b, two molecules involved in direction and branching of axon outgrowth, is controlled by Bcl11A-L. (PMID:19616629)
• BCL11A is a critical mediator of species-divergent globin switching (PMID:19657335)
• transcriptional silencing of gamma-globin genes by BCL11A involves long-range interactions and cooperation with SOX6 (PMID:20395365)
• SNPs in BCL11A and the HBS1L-MYB region did not show statistically significant correlations with HbFlevels.This suggests that the BCL11A and HBS1L-MYB loci have a minor effect on HbF level compared to the XmnI QTL in beta-thalassemia intermedia patients. (PMID:20472475)
• BCL11A is intimately involved in the transcriptional regulation of alpha and beta globins and may also regulate and be regulated by GATA-1 as part of a distinct activator or repressor protein complex. (PMID:20542454)
• characterize the prevalence of REL, BCL11A, and MYCN gains in a consecutive CLL series at the time of diagnosis; (ii) define the prognostic relevance of REL, BCL11A, and MYCN gains in CLL. (PMID:20575024)
• A subset of ALL cases bearing 14q32 LOH showed a down-regulation of miRNA 14q32 clusters linked to the submicroscopic chromosomal deletion. This had an inverse correlation with the expression of their target BCL11a. (PMID:20578197)
• through the interaction with Bcl11A, calcium/calmodulin-dependent serine protein kinase plays a role in axonogenesis, which may be related to brain anatomical characteristics in humans (PMID:20623620)
• BCL11A is a potent silencer of fetal hemoglobin. It controls the beta-globin gene cluster in concert with other factors. (PMID:21157349)
• no convincing associations were established to the surrogate measurements of beta cell function or insulin sensitivity in this Danish population-based study (PMID:21267535)
• A novel intronic SNP, rs7606173, associates with F-cell levels in sickle cell patients (P-value <1.81 x 10(-15)). (PMID:21326311)
• Administration of vascular endothelial growth factor (VEGF)-ZFP-TF may be neuroprotective and has potential as a safe and practical approach for management of motor disability in amyotrophic lateral sclerosis (ALS). (PMID:21864053)
• This study indicates a nominal role for JAZF1 and BCL11A variants in type 2 diabetes susceptibility in African-Americans. (PMID:22113416)
• frequency of rs4671393(G->A) was relatively high in patients with HbE/[beta]-thalassemia of Guangxi province of China, accompanying with high level of HbF; polymorphism of rs4671393 possibly prevents severe complications in patients with HbE/[beta]-thalassemia (PMID:22258351)
• Significantly distinct survival curves can be described in beta-thalassemia patients that are attributable to the genetic variants affecting fetal hemoglobin, BCL11A and intergenic HBS1L-MYB loci. (PMID:22271886)
• BCL11A is a novel TLX coregulator that might be involved in TLX-dependent gene regulation in the brain. (PMID:22675500)
• The C and T polymorphisms are found at the rs11886868 locus of the BCL11A gene in beta-thalassemia patients. The C polymorphism may be related to high Hemoblobin F expression in red blood cells. (PMID:22739175)
• Studies indicate that single nucleotide polymorphisms (SNPs) in regions of BCL11A and HBS1L-MYB intergenic polymorphism are the major modifiers of HbF in African Americans. (PMID:22936743)
• The G>A allele on the rs4671393 locus on chromosome 2 (BCL11A gene), did not show significant association with Hb F levels. (PMID:23094636)
• Regulators, including BCL11A,MYB, and KLF1, hold great promise to develop targeted and more effective approaches for HbF induction (PMID:23209159)
• Simvastatin and tBHQ suppress KLF1 and BCL11A gene expression and additively increase fetal hemoglobin in primary human erythroid cells. (PMID:23223429)
• The influence of the BCL11A polymorphism on the phenotype of patients with beta thalassemia could be affected by the beta globin locus control region and/or the Xmn1-HBG2 genotypic background. (PMID:23541515)
• BCL11A coordinates the hemoglobin switch and fetal hemoglobin silencing by assembling transcriptional corepressor complexes within the beta-globin cluster. (PMID:23576758)
• BCL11A overexpression predicts survival and relapse in non-small cell lung cancer and is modulated by microRNA-30a and gene amplification. (PMID:23758992)
• Data suggest that segregation of BCL11A haplotype 2 indicating an involvement of this locus in Hb F expression. (PMID:23777413)
• BCL11A contains F/YSXXLXXL/Y motifs that mediate highly selective binding to the LBDs of orphan nuclear receptors NR2E1/TLX, NR2E3/PNR and the NR2F/COUP-TF family. These motifs are required for BCL11A/COUP-TFII-mediated repression of foetal globin genes and a lncRNA termed Bgl3. The motifs are conserved in other Nuclear receptor cofactors such as NSD1, constituting a new signature motif related to LXXLL and the CoRNR box. (PMID:23975195)
• Immunohistochemical staining of mouse brain showed strong expression of BCL11A in the cortical regions and also in the pyramidal cell layers in the CA1 and CA3 regions of the hippocampus. (PMID:23975195)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bcl11aa	ENSDARG00000061352
mus_musculus	Bcl11a	ENSMUSG00000000861
rattus_norvegicus	Bcl11a	ENSRNOG00000007049

Paralogs (14): HIVEP2 (ENSG00000010818), HIVEP1 (ENSG00000095951), SALL4 (ENSG00000101115), ZNF516 (ENSG00000101493), SALL1 (ENSG00000103449), ZNF831 (ENSG00000124203), RREB1 (ENSG00000124782), HIVEP3 (ENSG00000127124), BCL11B (ENSG00000127152), ZNF219 (ENSG00000165804), SALL2 (ENSG00000165821), ZNF217 (ENSG00000171940), ZNF536 (ENSG00000198597), SALL3 (ENSG00000256463)

Protein

Protein identifiers

BCL11 transcription factor A — Q9H165 (reviewed: Q9H165)

Alternative names: B-cell CLL/lymphoma 11A, B-cell lymphoma/leukemia 11A, COUP-TF-interacting protein 1, Ecotropic viral integration site 9 protein homolog, Zinc finger protein 856

All UniProt accessions (16): Q9H165, A0A0J9YXG2, A0A0J9YY13, A0A0J9YYJ9, A0A2R8Y2E8, A0A2R8Y7B0, A0A2R8Y7W4, A0A2R8YCR5, A0A2R8YDS7, A0A2R8YDW6, A0A2R8YEK1, A0A2R8YGT9, A0A2R8YHH4, A0A2U3TZJ5, D9YZV9, D9YZW0

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor. Associated with the BAF SWI/SNF chromatin remodeling complex. Binds to the 5’-TGACCA-3’ sequence motif in regulatory regions of target genes, including a distal promoter of the HBG1 hemoglobin subunit gamma-1 gene. Involved in regulation of the developmental switch from gamma- to beta-globin, probably via direct repression of HBG1; hence indirectly repressing 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 NR2F2.

Subunit / interactions. Homotetrameric; self-associates via C2HC-type zinc finger domain. Interacts with MTA2, a component of the nucleosome remodeling and deacetylase (NuRD) repressor complex. Interacts (via its C2H2-type zinc finger domains 4, 5 and 6) with promoter region of gamma-globulin. Interacts with NR2F1, PIAS3, NR2F2 and NR2F6. Isoform 1, isoform 2 and isoform 3 form homodimers and heterodimers. Isoform 2 interacts with TBR1.

Subcellular location. Cytoplasm. Nucleus. Chromosome Nucleus matrix Cytoplasm. Nucleus Cytoplasm.

Tissue specificity. Expressed at high levels in brain, spleen thymus, bone marrow and testis. Expressed in CD34-positive myeloid precursor cells, B-cells, monocytes and megakaryocytes. Expression is tightly regulated during B-cell development. Expressed in fetal and adult brain, and in the plasmacytoid dendritic cell.

Post-translational modifications. Sumoylated with SUMO1.

Disease relevance. Chromosomal aberrations involving BCL11A are associated with B-cell malignancies. Translocation t(2;14)(p13;q32.3) causes BCL11A deregulation and overexpression. Intellectual developmental disorder with persistence of fetal hemoglobin (IDPFH) [MIM:617101] An autosomal dominant disorder characterized by delayed psychomotor development, intellectual disability, variable dysmorphic features, including microcephaly, downslanting palpebral fissures, strabismus, and external ear abnormalities, and asymptomatic persistence of fetal hemoglobin. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminus is involved in protein dimerization and in transactivation of transcription. The C-terminus of isoform 2 is necessary for isoform 2 interaction with TBR1. Zinc finger domains are necessary for sequence-specific binding to DNA.

Polymorphism. Genetic variation in BCL11A underlies the fetal hemoglobin quantitative trait locus 5 [MIM:142335]. It is associated with quantitative variation in the production of F cells, that is erythrocytes containing measurable amounts of fetal hemoglobin (HbF). In healthy adults, HbF is present at residual levels (less than 0.6% of total hemoglobin) with over twenty-fold variation. Ten to fifteen percent of adults in the upper tail of the distribution have HbF levels between 0.8% and 5.0%, a condition referred to as heterocellular hereditary persistence of fetal hemoglobin (hHPFH). Although these HbF levels are modest in otherwise healthy individuals, interaction of hHPFH with beta thalassemia or sickle cell disease can increase HbF output in these individuals to levels that are clinically beneficial.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9H165-1	1, BCL11A-XL, BCL11A extra long form	yes
Q9H165-2	2, BCL11A-L, BCL11A long form
Q9H165-3	3, BCL11A-S, BCL11A short form
Q9H165-6	6
Q9H165-8	7, BCL11A-XS, BCL11A eXtra short form

RefSeq proteins (33): NP_001350793, NP_001352538, NP_001392637, NP_001392638, NP_001392639, NP_001392640, NP_001392641, NP_001392642, NP_001392643, NP_001392644, NP_001392645, NP_001392647, NP_001392648, NP_001392649, NP_001392650, NP_001392651, NP_001392652, NP_001392653, NP_001392654, NP_001392655, NP_001392656, NP_001392657, NP_001392658, NP_001392659, NP_001392660, NP_001392661, NP_001392662, NP_001392663, NP_001392664, NP_001392665, NP_060484, NP_075044, NP_612569 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051497	Dev/Hematopoietic_TF	Family
IPR056438	Znf-C2H2_CTCF	Domain
IPR057448	BCL-11A_Znf_CCHC	Domain

Pfam: PF00096, PF23611, PF25491

UniProt features (103 total): binding site 16, modified residue 11, region of interest 10, sequence variant 10, compositionally biased region 8, zinc finger region 7, splice variant 7, sequence conflict 7, cross-link 6, helix 6, mutagenesis site 5, strand 5, turn 4, chain 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
6U9Q	X-RAY DIFFRACTION	1.83
9YLM	X-RAY DIFFRACTION	1.91
9YLO	X-RAY DIFFRACTION	1.97
9YLP	X-RAY DIFFRACTION	2.04
9E6R	X-RAY DIFFRACTION	2.09
9YLN	X-RAY DIFFRACTION	2.15
8DTN	X-RAY DIFFRACTION	2.2
9E6S	X-RAY DIFFRACTION	2.2
9YLL	X-RAY DIFFRACTION	2.38
5VTB	X-RAY DIFFRACTION	2.4
8DTU	X-RAY DIFFRACTION	2.45
6KI6	X-RAY DIFFRACTION	2.5
9B4P	X-RAY DIFFRACTION	2.56
8TLO	X-RAY DIFFRACTION	2.76
9E6T	X-RAY DIFFRACTION	2.78
8THO	SOLUTION NMR
9BV0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H165-F1	53.09	0.01

Antibody-complex structures (SAbDab): 2 — 8DTN, 8DTU

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (16): 48; 51; 66; 71; 744; 747; 760; 764; 772; 775; 788; 792 …

Post-translational modifications (17): 123, 86, 205, 271, 332, 337, 446, 447, 608, 625, 630, 701, 123, 164, 620, 634, 833

Mutagenesis-validated functional residues (5):

Position	Phenotype
46	abolishes self-association; when associated with a-57, a-60, a-61 and a-63.
57	abolishes self-association; when associated with a-46, a-60, a-61 and a-63.
60	impairs self-association. abolishes self-association; when associated with a-46, a-57, a-61 and a-63. reduces expression
61	abolishes self-association; when associated with a-46, a-57, a-60 and a-63. reduces expression in erythroid cells; when
63	impairs self-association. abolishes self-association; when associated with a-46, a-57, a-60 and a-61.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-9700645	ALK mutants bind TKIs
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-9933946	Formation of the embryonic stem cell BAF (esBAF) complex
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)
R-HSA-1643685	Disease
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-9700206	Signaling by ALK in cancer

MSigDB gene sets: 689 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, AHRARNT_01, GOBP_DENDRITE_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, FREAC2_01, GOBP_REGULATION_OF_COLLATERAL_SPROUTING, PAX4_01, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, JAEGER_METASTASIS_DN, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, AAGCCAT_MIR135A_MIR135B

GO Biological Process (17): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of gene expression (GO:0010628), positive regulation of neuron projection development (GO:0010976), negative regulation of neuron projection development (GO:0010977), protein sumoylation (GO:0016925), negative regulation of axon extension (GO:0030517), negative regulation of protein homooligomerization (GO:0032463), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of collateral sprouting (GO:0048671), positive regulation of collateral sprouting (GO:0048672), regulation of dendrite development (GO:0050773), negative regulation of dendrite extension (GO:1903860), negative regulation of neuron remodeling (GO:1904800), cellular response to L-glutamate (GO:1905232), negative regulation of dendrite development (GO:2000171), negative regulation of branching morphogenesis of a nerve (GO:2000173)

GO Molecular Function (14): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), transcription regulatory region nucleic acid binding (GO:0001067), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), transcription coregulator activity (GO:0003712), zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), DNA-binding transcription factor binding (GO:0140297), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear matrix (GO:0016363), SWI/SNF complex (GO:0016514), paraspeckles (GO:0042382), postsynapse (GO:0098794), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by ALK in cancer	2
SWI/SNF chromatin remodelers	2
Disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
transcription by RNA polymerase II	3
regulation of neuron projection development	3
negative regulation of cell growth	3
negative regulation of developmental growth	3
regulation of transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
neuron projection development	2
negative regulation of axonogenesis	2
collateral sprouting	2
regulation of collateral sprouting	2
dendrite development	2
negative regulation of developmental process	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
nucleic acid binding	2
transcription regulator activity	2
protein dimerization activity	2
nuclear lumen	2
negative regulation of DNA-templated transcription	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of cell projection organization	1
negative regulation of cell projection organization	1
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
regulation of axon extension	1
axon extension	1
negative regulation of protein oligomerization	1
regulation of protein homooligomerization	1
protein homooligomerization	1
positive regulation of DNA-templated transcription	1
positive regulation of cell growth	1
positive regulation of developmental growth	1
positive regulation of axonogenesis	1
regulation of developmental process	1
dendrite extension	1
regulation of dendrite extension	1
negative regulation of neuron maturation	1
neuron remodeling	1

Protein interactions and networks

STRING

2158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCL11A	A0A0J9YYA3	A0A0J9YYA3	956
BCL11A	SOX6	P35712	941
BCL11A	NR2F2	P24468	902
BCL11A	DNMT1	P26358	894
BCL11A	HBS1L	Q9Y450	894
BCL11A	HBB	P02023	894
BCL11A	GATA1	P15976	879
BCL11A	HBG1	P02096	870
BCL11A	KDM1A	O60341	865
BCL11A	BCL6	P41182	784
BCL11A	HBE1	P02100	775
BCL11A	ZFPM1	Q8IX07	765
BCL11A	ARID1A	O14497	757
BCL11A	SMARCC2	Q8TAQ2	749
BCL11A	EBF1	Q9UH73	729

IntAct

42 interactions, top by confidence:

A	B	Type	Score
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
UBXN4	UBE4A	psi-mi:“MI:0914”(association)	0.620
MBD3L1	CDK2AP1	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
RBBP7	EPOP	psi-mi:“MI:0914”(association)	0.530
MTA1	H3C1	psi-mi:“MI:0914”(association)	0.480
CDK6	BCL11A	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
BCL11A	CDK4	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CLTC	BCL11A	psi-mi:“MI:0407”(direct interaction)	0.440
G3BP2	BCL11A	psi-mi:“MI:0407”(direct interaction)	0.440
BCL11A		psi-mi:“MI:0915”(physical association)	0.400
BCL11A	FXR2	psi-mi:“MI:0915”(physical association)	0.370
BCL11A	TSC1	psi-mi:“MI:0915”(physical association)	0.370
YME1L1	BCL11A	psi-mi:“MI:0915”(physical association)	0.370
CDCA3	BCL11A	psi-mi:“MI:0915”(physical association)	0.370
BCL11A	ACTC1	psi-mi:“MI:0915”(physical association)	0.370
MTA2	ZBTB7A	psi-mi:“MI:0914”(association)	0.350
CEP192	WASL	psi-mi:“MI:0914”(association)	0.350
HDAC1		psi-mi:“MI:0914”(association)	0.350
HDAC2		psi-mi:“MI:0914”(association)	0.350
MAP3K20	MEIS1	psi-mi:“MI:0914”(association)	0.350
FGFR2	U2SURP	psi-mi:“MI:0914”(association)	0.350
MBD3L2	AHCYL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (189): BCL11A (Two-hybrid), BCL11A (Two-hybrid), BCL11A (Two-hybrid), GMCL1P1 (Two-hybrid), BCL11A (Biochemical Activity), BCL11A (Affinity Capture-Western), BCL11A (Affinity Capture-MS), BCL11A (Affinity Capture-MS), BCL11A (Affinity Capture-MS), BCL11A (Affinity Capture-MS), BCL11A (Affinity Capture-MS), BCL11A (Affinity Capture-MS), BCL11A (Affinity Capture-MS), BCL11A (Affinity Capture-MS), BCL11A (Affinity Capture-MS)

ESM2 similar proteins: A0JPB4, A1L1J6, A2VDW9, A4IFJ6, O00409, O08876, O08900, O13089, O15060, O15062, O42410, O57415, O60315, O75626, O89091, P14404, P25932, P36197, P37275, P55878, P55879, P81183, Q03267, Q0VDT2, Q13422, Q33BP8, Q3BJS3, Q3UH06, Q499D0, Q5R9W9, Q5T0B9, Q5ZLR2, Q5ZM39, Q60636, Q62255, Q62947, Q64318, Q6DBW0, Q6NRM0, Q6XDT4

Diamond homologs: A0A1V6NWD3, A0A2H1A5W4, A1L2U9, B0XS89, B1WAZ8, B1WBU4, P53243, P56270, P56670, P56671, P78871, Q00453, Q0IH98, Q0VCJ6, Q12132, Q4WXK4, Q6P882, Q96BR9, Q99PV8, Q9C0K0, Q9CWH1, Q9H165, Q9QYE3, Q9UPG8, Q9US36, Q9UTS5, A2A884, A2ANX9, A7Y7X5, B0X9H6, B0YDH7, E9PW05, E9PZZ1, G5EBU4, O15391, O60315, O62836, O75362, O77459, O95863

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
BCL11A	“down-regulates quantity by repression”	HBG1	“transcriptional regulation”
BCL11A	“down-regulates quantity by repression”	HBG2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	6	58.6×	6e-08
Regulation of TP53 Activity through Acetylation	5	58.6×	1e-06
NuRD complex assembly	10	36.1×	3e-11
RNA Polymerase I Transcription Initiation	6	34.5×	1e-06
Regulation of PTEN gene transcription	6	27.4×	2e-06
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	7	27.3×	4e-07
Interaction of NuRD complexes with transcription factors	8	26.0×	6e-08
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	6	22.5×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	6	93.8×	9e-09
negative regulation of transforming growth factor beta receptor signaling pathway	5	17.7×	7e-04
chromatin remodeling	8	11.9×	6e-05
chromatin organization	5	10.1×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — NHL.

Clinical variants and AI predictions

ClinVar

342 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	53
Likely pathogenic	40
Uncertain significance	173
Likely benign	32
Benign	11

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1177340	NM_022893.4(BCL11A):c.512_519del (p.Thr171fs)	Pathogenic
1177341	NM_022893.4(BCL11A):c.1345del (p.Glu449fs)	Pathogenic
1208340	NM_022893.4(BCL11A):c.310del (p.Gln104fs)	Pathogenic
1342337	NM_022893.4(BCL11A):c.1846_1847delinsA (p.Gly616fs)	Pathogenic
1397405	NM_022893.4(BCL11A):c.565_575del (p.Ala189fs)	Pathogenic
147996	GRCh38/hg38 2p16.1(chr2:55570578-60519844)x1	Pathogenic
1679411	NM_022893.4(BCL11A):c.3G>A (p.Met1Ile)	Pathogenic
1687104	NM_022893.4(BCL11A):c.35T>G (p.Leu12Ter)	Pathogenic
1703500	NM_022893.4(BCL11A):c.147del (p.Gln50fs)	Pathogenic
1804108	NM_022893.4(BCL11A):c.759_769del (p.Leu254fs)	Pathogenic
2126136	NM_022893.4(BCL11A):c.2T>A (p.Met1Lys)	Pathogenic
2497886	NM_022893.4(BCL11A):c.2362C>T (p.His788Tyr)	Pathogenic
253300	NM_022893.4(BCL11A):c.139A>C (p.Thr47Pro)	Pathogenic
253301	NM_022893.4(BCL11A):c.143G>T (p.Cys48Phe)	Pathogenic
253302	NM_022893.4(BCL11A):c.198C>A (p.His66Gln)	Pathogenic
253304	NM_022893.4(BCL11A):c.1775_1776insTGG (p.Gly592dup)	Pathogenic
2570606	NM_022893.4(BCL11A):c.1486G>T (p.Glu496Ter)	Pathogenic
2626885	NM_022893.4(BCL11A):c.875del (p.His292fs)	Pathogenic
2664349	NM_022893.4(BCL11A):c.1442del (p.Glu481fs)	Pathogenic
2664657	NM_022893.4(BCL11A):c.1576del (p.Glu526fs)	Pathogenic
3024309	NM_022893.4(BCL11A):c.1417G>T (p.Glu473Ter)	Pathogenic
3062626	GRCh37/hg19 2p16.1(chr2:60693746-60802307)x1	Pathogenic
3254642	NM_022893.4(BCL11A):c.230T>G (p.Leu77Ter)	Pathogenic
3255198	NM_022893.4(BCL11A):c.384A>G (p.Ala128=)	Pathogenic
3343957	NM_022893.4(BCL11A):c.1453G>T (p.Glu485Ter)	Pathogenic
3372531	NM_022893.4(BCL11A):c.28C>T (p.Gln10Ter)	Pathogenic
3775480	NM_022893.4(BCL11A):c.1576_1579del (p.Glu526fs)	Pathogenic
3906904	GRCh37/hg19 2p16.1(chr2:60760777-60789053)x1	Pathogenic
391343	NM_022893.4(BCL11A):c.263C>A (p.Ser88Ter)	Pathogenic
4055760	NM_022893.4(BCL11A):c.793del (p.Leu265fs)	Pathogenic

SpliceAI

1626 predictions. Top by Δscore:

Variant	Effect	Δscore
2:60513172:T:C	donor_gain	1.0000
2:60513181:T:C	donor_gain	1.0000
2:60545966:TTTAC:T	donor_loss	1.0000
2:60545967:TTA:T	donor_loss	1.0000
2:60545968:TACCT:T	donor_loss	1.0000
2:60545969:A:T	donor_loss	1.0000
2:60545970:C:CA	donor_loss	1.0000
2:60546296:CTCGG:C	acceptor_gain	1.0000
2:60546297:TCGG:T	acceptor_gain	1.0000
2:60546298:CGG:C	acceptor_gain	1.0000
2:60546298:CGGC:C	acceptor_gain	1.0000
2:60546299:GG:G	acceptor_gain	1.0000
2:60546300:GC:G	acceptor_loss	1.0000
2:60546301:C:CC	acceptor_gain	1.0000
2:60546301:C:CG	acceptor_loss	1.0000
2:60546302:T:A	acceptor_loss	1.0000
2:60546303:G:C	acceptor_gain	1.0000
2:60546307:T:C	acceptor_gain	1.0000
2:60546307:T:TC	acceptor_gain	1.0000
2:60462420:TTTAC:T	acceptor_gain	0.9900
2:60462423:ACCT:A	acceptor_loss	0.9900
2:60462424:CCT:C	acceptor_loss	0.9900
2:60462425:C:A	acceptor_loss	0.9900
2:60462425:C:CC	acceptor_gain	0.9900
2:60468726:A:C	donor_gain	0.9900
2:60468730:A:AC	donor_gain	0.9900
2:60468731:C:CC	donor_gain	0.9900
2:60513166:A:AC	donor_gain	0.9900
2:60513167:C:CC	donor_gain	0.9900
2:60546303:G:GC	acceptor_gain	0.9900

AlphaMissense

5530 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:60460448:A:G	W822R	1.000
2:60460448:A:T	W822R	1.000
2:60460458:G:C	H818Q	1.000
2:60460458:G:T	H818Q	1.000
2:60460459:T:C	H818R	1.000
2:60460459:T:G	H818P	1.000
2:60460460:G:C	H818D	1.000
2:60460460:G:T	H818N	1.000
2:60460468:A:G	L815P	1.000
2:60460485:A:C	F809L	1.000
2:60460485:A:T	F809L	1.000
2:60460486:A:G	F809S	1.000
2:60460487:A:G	F809L	1.000
2:60460487:A:T	F809I	1.000
2:60460497:A:C	C805W	1.000
2:60460498:C:A	C805F	1.000
2:60460498:C:G	C805S	1.000
2:60460498:C:T	C805Y	1.000
2:60460499:A:G	C805R	1.000
2:60460499:A:T	C805S	1.000
2:60460506:A:C	C802W	1.000
2:60460507:C:A	C802F	1.000
2:60460507:C:G	C802S	1.000
2:60460507:C:T	C802Y	1.000
2:60460508:A:G	C802R	1.000
2:60460508:A:T	C802S	1.000
2:60460536:A:C	H792Q	1.000
2:60460536:A:T	H792Q	1.000
2:60460538:G:A	H792Y	1.000
2:60460538:G:C	H792D	1.000

dbSNP variants (sampled 300 via entrez): RS1000016375 (2:60555428 A>T), RS1000019719 (2:60455929 T>A), RS1000026756 (2:60499532 T>A), RS1000035914 (2:60505281 G>A), RS1000078812 (2:60499907 G>A,T), RS1000107559 (2:60516877 G>C), RS1000144354 (2:60479628 G>A,C), RS1000192633 (2:60471756 T>A,G), RS1000216826 (2:60482234 T>C), RS1000272108 (2:60476291 A>C,T), RS1000297357 (2:60494413 T>A), RS1000352603 (2:60485564 G>A), RS1000359126 (2:60527713 T>A), RS1000366287 (2:60485889 A>C,G), RS1000409247 (2:60492558 C>A,T)

Disease associations

OMIM: gene MIM:606557 | disease phenotypes: MIM:617101, MIM:617600, MIM:213000, MIM:217990, MIM:174200

GenCC curated gene-disease

Disease	Classification	Inheritance
Dias-Logan syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Dias-Logan syndrome	Definitive	AD

Mondo (6): Dias-Logan syndrome (MONDO:0014914), intellectual disability, autosomal dominant 45 (MONDO:0030910), intellectual disability (MONDO:0001071), isolated cerebellar hypoplasia/agenesis (MONDO:0008939), corpus callosum, agenesis of (MONDO:0009022), postaxial polydactyly (MONDO:0020927)

Orphanet (4): Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246), Isolated corpus callosum agenesis (Orphanet:200), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000378	Cupped ear
HP:0000396	Overfolded helix
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000494	Downslanted palpebral fissures
HP:0000592	Blue sclerae
HP:0000729	Autistic behavior
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001382	Joint hypermobility
HP:0001744	Splenomegaly
HP:0001746	Asplenia
HP:0001923	Reticulocytosis
HP:0002027	Abdominal pain
HP:0002070	Limb ataxia
HP:0002078	Truncal ataxia
HP:0002113	Pulmonary infiltrates
HP:0002136	Broad-based gait
HP:0002360	Sleep disturbance
HP:0002829	Arthralgia
HP:0003577	Congenital onset

GWAS associations

111 associations (top):

Study	Trait	p-value
GCST000069_2	F-cell distribution	6.000000e-31
GCST000150_2	Fetal hemoglobin levels	7.000000e-35
GCST000503_15	Mean corpuscular volume	1.000000e-14
GCST000532_3	Beta thalassemia/hemoglobin E disease	1.000000e-10
GCST000545_1	Fetal hemoglobin levels	1.000000e-29
GCST000545_3	Fetal hemoglobin levels	1.000000e-07
GCST000712_6	Type 2 diabetes	3.000000e-15
GCST000982_10	F-cell distribution in sickle cell anaemia	2.000000e-07
GCST000982_11	F-cell distribution in sickle cell anaemia	2.000000e-16
GCST001048_3	Monocyte early outgrowth colony forming units	4.000000e-06
GCST001287_2	Attention deficit hyperactivity disorder	7.000000e-06
GCST001765_38	Red blood cell traits	4.000000e-13
GCST001862_1	Sickle cell anemia (haemolysis)	9.000000e-07
GCST001971_1	Hypersomnia (HLA-DQB1*06:02 negative)	1.000000e-06
GCST002352_54	Type 2 diabetes	3.000000e-06
GCST002481_14	Acne (severe)	2.000000e-06
GCST002536_1	Hemoglobin A2 levels in sickle cell anemia	3.000000e-10
GCST002541_38	Menarche (age at onset)	3.000000e-08
GCST002687_1	Fetal hemoglobin levels in sickle cell anemia	4.000000e-53
GCST003122_5	Hemoglobin levels	3.000000e-130
GCST003818_16	Resting heart rate	9.000000e-09
GCST004004_30	Mean corpuscular volume	3.000000e-12
GCST004093_27	Prostate-specific antigen levels	6.000000e-19
GCST004136_27	Methadone dose in opioid dependence	6.000000e-06
GCST004601_24	Red blood cell count	7.000000e-28
GCST004602_84	Mean corpuscular volume	9.000000e-30
GCST004611_12	High light scatter reticulocyte count	3.000000e-09
GCST004612_169	High light scatter reticulocyte percentage of red cells	5.000000e-09
GCST004621_49	Red cell distribution width	8.000000e-21
GCST004628_145	Immature fraction of reticulocytes	2.000000e-12

EFO canonical traits (29, from GWAS)

EFO ID	Trait name
EFO:0004576	fetal hemoglobin measurement
EFO:0004506	monocyte early outgrowth colony forming unit
EFO:0005845	hemoglobin A2 measurement
EFO:0004703	age at menarche
EFO:0004509	hemoglobin measurement
EFO:0007907	methadone dose measurement
EFO:0004305	erythrocyte count
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009184	heart rate response to exercise
EFO:0009185	heart rate response to recovery post exercise
EFO:0007796	parental longevity
EFO:0009270	heel bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0008008	lower urinary tract symptom
EFO:0008328	chronotype measurement
EFO:0007778	urinary albumin to creatinine ratio
EFO:0005670	smoking initiation
EFO:0004874	memory performance
EFO:0009695	household income
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0009819	comparative body size at age 10, self-reported
EFO:0009749	age at first sexual intercourse measurement
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D061085	Agenesis of Corpus Callosum	C10.500.034; C16.131.666.034; C23.300.008
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C562568	Cerebellar Hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5498502 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1427407	BCL11A		0.00	0
rs766432	BCL11A		0.00	0
rs4671393	BCL11A		0.00	0
rs6545816	BCL11A		0.00	0
rs6706648	BCL11A		0.00	0

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, affects cotreatment	7
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases expression, affects methylation	2
Formaldehyde	decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tretinoin	decreases expression	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
geraniol	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	decreases expression	1
hydroquinone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
beta-methylcholine	affects expression	1
pentanal	increases expression	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1

Cellosaurus cell lines

9 cell lines: 5 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0H5	SEES3-1V human BCL11A, clone1	Embryonic stem cell	Male
CVCL_A0H6	SEES3-1V human BCL11A, clone2	Embryonic stem cell	Male
CVCL_A0H7	SEES3-1V human BCL11A, clone3	Embryonic stem cell	Male
CVCL_B8BV	Abcam HCT 116 BCL11A KO	Cancer cell line	Male
CVCL_B8SU	Abcam MCF-7 BCL11A KO	Cancer cell line	Female
CVCL_B9DZ	Abcam A-549 BCL11A KO	Cancer cell line	Male
CVCL_SE87	HAP1 BCL11A (-) 1	Cancer cell line	Male
CVCL_SE88	HAP1 BCL11A (-) 2	Cancer cell line	Male
CVCL_XV62	HEK293 eGFP-BCL11A	Transformed cell line	Female

Clinical trials (associated diseases)

197 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders