MS4A2
protein-codingmembrane spanning 4-domains A2, the group of Membrane spanning 4-domains
Gene summary
The allergic response involves the binding of allergen to receptor-bound IgE followed by cell activation and the release of mediators responsible for the manifestations of allergy. The IgE-receptor, a tetramer composed of an alpha, beta, and 2 disulfide-linked gamma chains, is found on the surface of mast cells and basophils. This gene encodes the beta subunit of the high affinity IgE receptor which is a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. This family member is localized to 11q12, among a cluster of membrane-spanning 4A gene family members. Alternative splicing results in multiple transcript variants encoding distinct proteins. Additional transcript variants have been described but require experimental validation. [provided by RefSeq, Mar 2012]
- FCER1B
- IGER
- APY
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007817
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MS4A2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000139.5. 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 | 1 | 1 | 2 | |||
| missense | 37 | 5 | 2 | 44 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 37 | 6 | 3 | 46 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000130.1 | 7 | MANE Select | |
| Ensembl | ENSP00000278888.3 | 7 | MANE Select | |
| RefSeq | NP_001243845.1 | 6 | Standard | |
| Ensembl | ENSP00000433311.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fc epsilon RI signaling pathway - Homo sapiens (human)
- Asthma - Homo sapiens (human)
- Sphingolipid signaling pathway - Homo sapiens (human)
- Phospholipase D signaling pathway - Homo sapiens (human)
- Fc Epsilon Receptor I Signaling in Mast Cells
Biological Process
- inflammatory response
- immune response
- Fc-epsilon receptor signaling pathway
Molecular Function
- IgE binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- external side of plasma membrane
- Fc-epsilon receptor I complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000278888
- Coding exons
- 7
- Length
- 7711
- Individuals with no LoFs
- 124940
- Homozygous LoFs
- 8
- Heterozygous LoFs
- 798
- Defined
- 125746
- p
- 0.00321
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.309 | 133 | 123 | 1.08 | 0.00000555 | 1568 |
| Missense (PolyPhen) | 44 | 34.698 | 1.2681 | 467 | ||
| Synonymous | -0.677 | 50 | 44.3 | 1.13 | 0.00000210 | 482 |
| Loss of Function | -0.332 | 12 | 10.8 | 1.11 | 4.59e-7 | 140 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.022 | 0.022 | notable |
| European (Non-Finnish) | 0.0027 | 0.0027 | notable |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.0020 | 0.0020 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: High affinity receptor that binds to the Fc region of immunoglobulins epsilon. Aggregation of FCER1 by multivalent antigens is required for the full mast cell response, including the release of preformed mediators (such as histamine) by degranulation and de novo production of lipid mediators and cytokines. Also mediates the secretion of important lymphokines. Binding of allergen to receptor-bound IgE leads to cell activation and the release of mediators responsible for the manifestations of allergy.;
Recessive Scores
- pRec
- 0.152
Intolerance Scores
- LoFtool
- 0.793
- RVIS EVS
- 0.91
- RVIS percentile EVS
- 89.44
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.584
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |