BICRA

Chr 19

BRD4 interacting chromatin remodeling complex associated protein

Also known as: CSS12, GLTSCR1, SMARCK1

NCBI Gene: 29998ENSG00000063169UniProt: Q9NZM4

Enables transcription regulator activator activity. Involved in positive regulation of DNA-templated transcription. Located in nucleus. Part of SWI/SNF complex. Implicated in Coffin-Siris syndrome 12. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

UniProtCoffin-Siris syndrome 12
510
ClinVar variants
52
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— BICRA
🧬
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.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 367 VUS of 510 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.30LOEUF
pLI 0.983
Z-score 4.66
OE 0.14 (0.07–0.30)
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.
2.54Z-score
OE missense 0.75 (0.70–0.80)
618 obs / 823.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.14 (0.07–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.70–0.80)
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.1.09
0≤1.21.6
LoF obs/exp: 5 / 34.5Missense obs/exp: 618 / 823.0Syn Z: -1.41

ClinVar Variant Classifications

510 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic21
VUS367
Likely Benign74
Benign13
Conflicting4
31
Pathogenic
21
Likely Pathogenic
367
VUS
74
Likely Benign
13
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
1
14
0
31
Likely Pathogenic
9
1
11
0
21
VUS
8
336
21
2
367
Likely Benign
0
37
2
35
74
Benign
1
3
4
5
13
Conflicting
—4
Total343785242510

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

View 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.

Gene2Phenotype Curations

BICRA-related developmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — BICRA
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms.
Barish S et al.·Am J Hum Genet
2020Functional
Delineation of the adult phenotype of Coffin-Siris syndrome in 35 individuals.
Schmetz A et al.·Hum Genet
2024
A de novo variant of BICRA results in Coffin-Siris syndrome 12.
Tu Y et al.·Mol Genet Genomic Med
2023Case report
Identification of a novel BICRA variant leading to the newly described Coffin-Siris syndrome 12.
Asadauskaitė G et al.·Brain Dev
2023Case report
Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical Region.
Guadagnolo D et al.·Genes (Basel)
2023Review
Beyond Neurodevelopmental Delay: BICRA-Related Coffin-Siris Syndrome 12 with Severe Intestinal Dysmotility and Recurrent Pneumothorax.
Wang H·Genes (Basel)
2026Case report
Retrospective analysis of a clinical exome sequencing cohort reveals the mutational spectrum and identifies candidate disease-associated loci for BAFopathies.
Chen CA et al.·Genet Med
2022Cohort
ARID2, a milder cause of Coffin-Siris Syndrome? Broadening the phenotype with 17 additional individuals.
Schrier Vergano SA·Am J Med Genet A
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools