BCL11A

Chr 2AD

BCL11 transcription factor A

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

NCBI Gene: 53335 ENSG00000119866 UniProt: Q9H165 OMIM: 606557

The protein is a C2H2 zinc-finger transcription factor that regulates hematopoietic cell differentiation and is normally down-regulated during this process. Loss-of-function mutations cause Dias-Logan syndrome through an autosomal dominant inheritance pattern. The high pLI score (0.97) and low LOEUF score (0.32) indicate strong intolerance to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Dias-Logan syndromeMIM #617101

UniProtIntellectual developmental disorder with persistence of fetal hemoglobin

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Dias-Logan syndrome · AD · ClinGen 2020

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

148

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.32

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — BCL11A

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.12 (0.06–0.32)

0≤0.351.4

Missense OE?0.54 (0.49–0.59)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 3 / 24.1Missense obs/exp: 296 / 548.8Syn Z: 2.10

Background carrier burden — how many people carry a rare variant somewhere in BCL11A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 98

993 rare PASS variants

Rare truncating (LoF)

1 in 2,300

45 rare PASS variants

Rare synonymous (reference)

1 in 100

518 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BCL11A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 4,400
South Asian	~43k	1 in 84	1 in 1,100
Remaining (unassigned)	~30k	1 in 100	1 in 820
European (Finnish)	~27k	1 in 250	1 in 4,000
Admixed American	~22k	1 in 120	1 in 400
African / African American	~21k	1 in 130	1 in 1,300
East Asian	~20k	1 in 140	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 370	none seen
Middle Eastern	~2,884	1 in 130	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 4 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: 3 of 4 (exon 1 below).? see exons ↓