BCOR

Chr XXLD

BCL6 corepressor

Also known as: ANOP2, MAA2, MCOPS2

NCBI Gene: 54880 ENSG00000183337 UniProt: Q6W2J9 OMIM: 300485

BCOR encodes a transcriptional corepressor that inhibits gene expression by recruiting histone deacetylases to promoter regions and regulating chromatin modifications. X-linked dominant mutations cause microphthalmia, syndromic 2, affecting eye development and other systems. The gene is highly constrained against loss-of-function variation (pLI 1.0, LOEUF 0.14), indicating intolerance to protein-truncating variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene was identified as an interacting corepressor of BCL6, a POZ/zinc finger transcription repressor that is required for germinal center formation and may influence apoptosis. This protein selectively interacts with the POZ domain of BCL6, but not with eight other POZ proteins. Specific class I and II histone deacetylases (HDACs) have been shown to interact with this protein, which suggests a possible link between the two classes of HDACs. Several transcript variants encoding different isoforms have been found for this gene. A pseudogene of this gene is found on chromosome Y.[provided by RefSeq, Jun 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Microphthalmia, syndromic 2MIM #300166

XLD

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · microphthalmia, syndromic 2 · XL · 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

196

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.14

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — BCOR

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

LoF Constraint?

0.14LOEUF

pLI 1.000

Z-score 5.91

OE 0.04 (0.02–0.14)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

1.88Z-score

OE missense 0.81 (0.75–0.86)

601 obs / 745.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.04 (0.02–0.14)

0≤0.351.4

Missense OE?0.81 (0.75–0.86)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 2 / 44.6Missense obs/exp: 601 / 745.4Syn Z: -0.60

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

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,380 rare PASS variants

Rare truncating (LoF)

1 in 7,700

24 rare PASS variants

Rare synonymous (reference)

1 in 58

658 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BCOR. 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)	~561k	1 in 76	1 in 18,000
South Asian	~36k	1 in 53	1 in 2,500
Remaining (unassigned)	~31k	1 in 50	1 in 4,700
European (Finnish)	~27k	1 in 180	≈ 1 in 18,000
Admixed American	~23k	1 in 56	≈ 1 in 11,000
African / African American	~21k	1 in 51	1 in 1,100
East Asian	~20k	1 in 53	1 in 770
Ashkenazi Jewish	~13k	1 in 460	none seen
Middle Eastern	~2,758	1 in 41	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): All 14 coding exons well covered in gnomAD exomes and genomes.? see exons ↓