BCL11A

Chr 2

BCL11 transcription factor A

Also known as: CTIP1, DILOS, EVI9, HBFQTL5, SMARCM1, ZNF856

NCBI Gene: 53335 ENSG00000119866 UniProt: Q9H165

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. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder with persistence of fetal hemoglobin

343

ClinVar variants

116

Pathogenic / LP

0.97

pLI score· haploinsufficient

Active trials

Clinical Summary— BCL11A

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Gene-Disease Validity (ClinGen)

Dias-Logan syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

116 Pathogenic / Likely Pathogenic· 172 VUS of 343 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.32LOEUF

pLI 0.970

Z-score 3.98

OE 0.12 (0.06–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

3.84Z-score

OE missense 0.54 (0.49–0.59)

296 obs / 548.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.06–0.32)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.54 (0.49–0.59)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	29	7	29	1	66
Likely Pathogenic	27	9	14	0	50
VUS	2	146	19	5	172
Likely Benign	0	11	0	27	38
Benign	0	3	5	4	12
Conflicting	—				5
Total	58	176	67	37	343

BCL11A

Primary Disease Associations & Inheritance

Population Genetics & Constraint

ClinVar Variant Classifications

Classification Summary

Curated Variants Distribution

Protein Context — Lollipop Plot

DECIPHER · Gene2Phenotype

Gene2Phenotype Curations

OMIM — Genotype-Phenotype

Gene Overview

ClinGen Curation

Disease Associations

External Resources

Variant Interpretation

Population Databases