BRMS1
protein-codingBRMS1 transcriptional repressor and anoikis regulator
Gene summary
This gene reduces the metastatic potential, but not the tumorogenicity, of human breast cancer and melanoma cell lines. The protein encoded by this gene localizes primarily to the nucleus and is a component of the mSin3a family of histone deacetylase complexes (HDAC). The protein contains two coiled-coil motifs and several imperfect leucine zipper motifs. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.8 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 BRMS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015399.4. 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 | 1 | ||||
| missense | 43 | 43 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 50 | 0 | 1 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056214.1 | 9 | MANE Select | |
| Ensembl | ENSP00000353042.3 | 9 | MANE Select | |
| RefSeq | NP_001020128.1 | 9 | Standard | |
| Ensembl | ENSP00000396052.2 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- HDACs deacetylate histones
- Chromatin modifying enzymes
- Chromatin organization
Biological Process
- negative regulation of transcription by RNA polymerase II
- apoptotic process
- histone deacetylation
- negative regulation of NF-kappaB transcription factor activity
- regulation of apoptotic process
Molecular Function
- histone deacetylase activity
- protein binding
- histone deacetylase binding
- NF-kappaB binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- Sin3-type complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000425825
- Coding exons
- 9
- Length
- 7793
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 34
- Defined
- 125748
- p
- 0.000135
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.107 | 166 | 170 | 0.977 | 0.0000101 | 1880 |
| Missense (PolyPhen) | 47 | 51.471 | 0.91314 | 592 | ||
| Synonymous | 0.565 | 63 | 69.0 | 0.913 | 0.00000406 | 543 |
| Loss of Function | 1.13 | 13 | 18.2 | 0.715 | 9.59e-7 | 196 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00038 | 0.00037 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000079 | 0.000079 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional repressor. Down-regulates transcription activation by NF-kappa-B by promoting the deacetylation of RELA at 'Lys-310'. Promotes HDAC1 binding to promoter regions. Down- regulates expression of anti-apoptotic genes that are controlled by NF-kappa-B. Promotes apoptosis in cells that have inadequate adherence to a substrate, a process called anoikis, and may thereby inhibit metastasis. May be a mediator of metastasis suppression in breast carcinoma. {ECO:0000269|PubMed:14581478, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:20830743}.;
Recessive Scores
- pRec
- 0.135
Intolerance Scores
- LoFtool
- 0.157
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.930
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |