BCL6B

Chr 17

BCL6B transcription repressor

Also known as: BAZF, ZBTB28, ZNF62

NCBI Gene: 255877 ENSG00000161940 UniProt: Q8N143 OMIM: 608992

BCL6B encodes a sequence-specific transcriptional repressor that functions in association with BCL6 and is involved in early B-cell development and regulation of inflammatory and immune responses. Mutations cause autosomal dominant developmental delay with variable intellectual disability, behavioral abnormalities, and dysmorphic features. The gene shows moderate constraint against loss-of-function variants, consistent with its role in neurodevelopment.

OMIM ResearchSummary from RefSeq, UniProt

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including regulation of gene expression; regulation of inflammatory response; and type 2 immune response. Predicted to be located in nucleus. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.59

Clinical Summary— BCL6B

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

26 VUS of 29 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.047

Z-score 2.90

OE 0.30 (0.16–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.96Z-score

OE missense 0.85 (0.77–0.94)

268 obs / 316.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.16–0.59)

0≤0.351.4

Missense OE?0.85 (0.77–0.94)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 6 / 20.0Missense obs/exp: 268 / 316.2Syn Z: 0.88

This gene — mechanism propensity

0.74top 25%

GOF

0.6149th %ile

LOF

0.4431th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

29 submitted variants in ClinVar

ClinVar

Classification Summary

VUS26

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	26	26
Likely Benign	0	0
Benign	0	0
Total	26	26

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

19 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap BCL6B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →