BICRA

protein-coding

BRD4 interacting chromatin remodeling complex associated protein, the group of GBAF complex

Gene summary

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]

Previous symbols:

GLTSCR1

MANE transcript

NM_001394372.1

Inheritance

ClinVar variants

P:52U:442B:170

Top phenotype

Coffin-Siris syndrome

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr19:47,608,196-47,703,277

External References & Databases

Ensembl (ENSG00000063169)

Transcript & Mutation Effects

hg38 • Region Span ~95.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Coffin-Siris syndrome 12STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0025699

Submitter: G2P

Coffin-Siris syndrome 12STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0025699

Submitter: PanelApp Australia

Coffin-Siris syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015452

Submitter: ClinGen

*BICRA*, encoding a SWI/SNF chromatin remodeling complex subunit, was first reported in relation to autosomal dominant Coffin-Siris syndrome in 2020 (Barish et al., PMID: 33232675). Affected individuals exhibit neurodevelopmental phenotypes that include developmental delay, mild to moderate intellectual disability, autism spectrum disorder, and other behavioral abnormalities. While most affected individuals have variable dysmorphic facial features, the coarse facial features and fifth digit/nail hypoplasia frequently seen in other forms of Coffin-Siris syndrome are often absent. Eleven truncating variants (frameshift, nonsense) that have been reported in 11 probands in five publications (PMIDs: 33232675, 36437209, 37485815, 38117302, 38867597) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. Most reported variants occur *de novo*. The mechanism of pathogenicity is loss of function. Two individuals with *de novo* missense variants have also been reported (PMID: 33232675) but were not scored in this curation due to lack of functional data; without this information, it is uncertain whether these variants are acting via a similar or different mechanism as the other scored variants. This gene-disease relationship is also supported by experimental evidence, including biochemical function and protein interactions. Several other members of the SWI/SNF family of chromatin remodeling complexes have been involved in Coffin-Siris syndrome, including *SMARCA4*, *SMARCB1*, *SMARCC2*, *SMARCD1*, *SMARCE1*, *DPF2*, *ARID1A*, *ARID1B*, and *ARID2*. Variants in *SMARCA2*, another member of the SWI/SNF complex, cause a related disorder, Nicolaides-Baraitser syndrome. BICRA (BRD4 interacting chromatin remodeling complex associated protein) interacts with BRD4, a protein implicated in intellectual disability, and bridges it to the SWI/SNF complex. In summary, there is definitive evidence supporting the relationship between *BICRA* and autosomal dominant Coffin-Siris syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on November 20, 2024 (SOP Version 11).

Coffin-Siris syndrome 12MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0025699

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BICRA variants in ClinVar

12 Conditions Cataloged

not specifiedTotal: 384

not providedTotal: 254

Coffin-Siris syndrome 12Total: 77

BICRA-related disorderTotal: 26

BICRA-related Coffin-Siris syndromeTotal: 1

CSS12 + schizoaffective disorder, bipolar type/adult-onset psychiatric conditionTotal: 1

Neurodevelopmental disorderTotal: 1

GLTSCR1-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394372.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	104 clinvar	4 clinvar	115
missense	1 clinvar	2 clinvar	418 clinvar	58 clinvar	3 clinvar	482
nonsense	5 clinvar	9 clinvar	3 clinvar			17
start loss						0
frameshift	20 clinvar	14 clinvar	9 clinvar			43
splice donor/acceptor (+/-2bp)	1 clinvar		5 clinvar		1 clinvar	7
Total	27	25	442	162	8	664

Highest pathogenic variant AF is 0.0006381764

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394372.1	RefSeq	NP_001381301.1	13	MANE Select
ENST00000594866.3	Ensembl	ENSP00000469738.2	13	MANE Select
NM_015711.3	RefSeq	NP_056526.3	13	Standard
ENST00000396720.7	Ensembl	ENSP00000379946.2	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of transcription, DNA-templated

Molecular Function

transcription coactivator activity
protein binding

Cellular Component

nucleus
SWI/SNF complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396720
Coding exons: 13
Length: 95081
Individuals with no LoFs: 120322
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 120324
p: 0.00000831

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.54	618	823	0.751	0.0000561	9533
Missense (PolyPhen)		123	201.36	0.61084		2114
Synonymous	-1.41	460	423	1.09	0.0000355	3509
Loss of Function	4.66	5	34.5	0.145	0.00000149	429

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000062	0.000057	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000096	0.0000092	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:29374058). May play a role in BRD4-mediated gene transcription (PubMed:21555454). {ECO:0000269|PubMed:21555454, ECO:0000269|PubMed:29374058}.;

Recessive Scores

pRec: 0.125

Essentials

Essential (gene trap): N