BCAR1
protein-codingBCAR1 scaffold protein, Cas family member, the group of Cas scaffold proteins
Gene summary
The protein encoded by this gene is a member of the Crk-associated substrate (CAS) family of scaffold proteins, characterized by the presence of multiple protein-protein interaction domains and many serine and tyrosine phosphorylation sites. The encoded protein contains a Src-homology 3 (SH3) domain, a proline-rich domain, a substrate domain which contains 15 repeat of the YxxP consensus phosphorylation motif for Src family kinases, a serine-rich domain, and a bipartite Src-binding domain, which can bind both SH2 and SH3 domains. This adaptor protein functions in multiple cellular pathways, including in cell motility, apoptosis and cell cycle control. Dysregulation of this gene can have a wide range of effects, affecting different pathways, including cardiac development, vascular smooth muscle cells, liver and kidney function, endothelial migration, and cancer. [provided by RefSeq, Sep 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~39.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to BCAR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014567.5. 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 | 2 | 5 | 5 | 12 | ||
| missense | 213 | 8 | 7 | 228 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 0 | 1 | 218 | 13 | 12 | 244 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055382.2 | 7 | MANE Select | |
| Ensembl | ENSP00000162330.5 | 7 | MANE Select | |
| RefSeq | NP_001164185.1 | 7 | Standard | |
| RefSeq | NP_001164186.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Focal adhesion - Homo sapiens (human)
- Chemokine signaling pathway - Homo sapiens (human)
- Regulation of actin cytoskeleton - Homo sapiens (human)
- Rap1 signaling pathway - Homo sapiens (human)
- Bacterial invasion of epithelial cells - Homo sapiens (human)
Biological Process
- regulation of cell growth
- actin filament organization
- cell adhesion
- epidermal growth factor receptor signaling pathway
- G protein-coupled receptor signaling pathway
Molecular Function
- protein binding
- SH3 domain binding
- protein kinase binding
Cellular Component
- ruffle
- cytoplasm
- cytosol
- plasma membrane
- focal adhesion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000418647
- Coding exons
- 7
- Length
- 39024
- Individuals with no LoFs
- 125526
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125528
- p
- 0.00000797
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.594 | 609 | 569 | 1.07 | 0.0000383 | 5733 |
| Missense (PolyPhen) | 303 | 301.62 | 1.0046 | 2968 | ||
| Synonymous | -2.39 | 320 | 270 | 1.18 | 0.0000202 | 2005 |
| Loss of Function | 4.71 | 3 | 31.5 | 0.0952 | 0.00000178 | 325 |
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 | 0.000065 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000098 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion. Implicated in induction of cell migration. Overexpression confers antiestrogen resistance on breast cancer cells. {ECO:0000269|PubMed:12832404, ECO:0000269|PubMed:17038317}.;
Intolerance Scores
- LoFtool
- 0.158
- RVIS EVS
- 1.53
- RVIS percentile EVS
- 95.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.832
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |