BCAR3

protein-coding

BCAR3 adaptor protein, NSP family member, the group of SH2 domain containing|NSP adaptor proteins

Gene summary

Breast tumors are initially dependent on estrogens for growth and progression and can be inhibited by anti-estrogens such as tamoxifen. However, breast cancers progress to become anti-estrogen resistant. Breast cancer anti-estrogen resistance gene 3 was identified in the search for genes involved in the development of estrogen resistance. The gene encodes a component of intracellular signal transduction that causes estrogen-independent proliferation in human breast cancer cells. The protein contains a putative src homology 2 (SH2) domain, a hall mark of cellular tyrosine kinase signaling molecules, and is partly homologous to the cell division cycle protein CDC48. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

MANE transcript

NM_003567.4

Inheritance

—

ClinVar variants

U:150B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr1:93,561,741-93,847,150

External References & Databases

Ensembl (ENSG00000137936)

Transcript & Mutation Effects

hg38 • Region Span ~285.4 kb

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GenCC 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 BCAR3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 147

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003567.4. 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			1 clinvar		1 clinvar	2
missense			146 clinvar	7 clinvar	2 clinvar	155
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	150	7	3	160

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 76 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003567.4	RefSeq	NP_003558.1	11	MANE Select
ENST00000260502.11	Ensembl	ENSP00000260502.6	11	MANE Select
NM_001261408.2	RefSeq	NP_001248337.1	11	Standard
NM_001261409.1	RefSeq	NP_001248338.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGFR1
Regulation of CDC42 activity

Biological Process

lens morphogenesis in camera-type eye
signal transduction
small GTPase mediated signal transduction
positive regulation of peptidyl-serine phosphorylation
response to drug

Molecular Function

guanyl-nucleotide exchange factor activity
protein binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370244
Coding exons: 11
Length: 285360
Individuals with no LoFs: 125666
Homozygous LoFs: 0
Heterozygous LoFs: 82
Defined: 125748
p: 0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.302	479	498	0.962	0.0000299	5398
Missense (PolyPhen)		162	173.21	0.93529		1895
Synonymous	0.918	187	204	0.918	0.0000132	1651
Loss of Function	4.48	8	37.7	0.212	0.00000221	390

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.00098	notable
Latino/Admixed American	0.00046	0.00046	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000096	0.000092	rare
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.00016	0.00016	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as an adapter protein and couple activated growth factor receptors to a signaling pathway that regulates the proliferation in breast cancer cells. When overexpressed, it confers anti-estrogen resistance in breast cancer cell lines. May also be regulated by cellular adhesion to extracellular matrix proteins. {ECO:0000269|PubMed:9582273}.;

Recessive Scores

pRec: 0.165

Intolerance Scores

LoFtool: 0.683
RVIS EVS: 0.26
RVIS percentile EVS: 69.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.863

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium