BICRA

Chr 19AD

BRD4 interacting chromatin remodeling complex associated protein

Also known as: CSS12, GLTSCR1, SMARCK1

The BICRA protein is a component of the SWI/SNF chromatin remodeling complex that alters DNA-histone contacts within nucleosomes in an ATP-dependent manner to regulate gene transcription. Mutations cause Coffin-Siris syndrome 12, a neurodevelopmental disorder with intellectual disability and distinctive facial features, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.98), indicating that most pathogenic variants are likely de novo mutations.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.301 OMIM phenotype
Clinical SummaryBICRA
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Gene-Disease Validity (ClinGen)
Coffin-Siris syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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GeneReview available — BICRA
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.983
Z-score 4.66
OE 0.14 (0.070.30)
Highly constrained

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

Missense Constraint
2.54Z-score
OE missense 0.75 (0.700.80)
618 obs / 823.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.14 (0.070.30)
00.351.4
Missense OE0.75 (0.700.80)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 5 / 34.5Missense obs/exp: 618 / 823.0Syn Z: -1.41
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongBICRA-related developmental disorderLOFAD
DN
0.20100th %ile
GOF
0.3193th %ile
LOF
0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.30

Literature Evidence

LOFWe conclude that haploinsufficiency of BICRA leads to a unique SSRIDD in humans whose phenotypes overlap with those previously reported.PMID:33232675

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BICRA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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