LILRB4
protein-codingleukocyte immunoglobulin like receptor B4, the group of CD molecules|Inhibitory leukocyte immunoglobulin like receptors
Gene summary
This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a negative signal that inhibits stimulation of an immune response. The receptor can also function in antigen capture and presentation. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. Multiple transcript variants encoding different isoforms have been found for this gene. [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 ~26.5 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 LILRB4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001278426.4. 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 | 3 | 4 | |||
| missense | 6 | 1 | 7 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 10 | 10 | ||||
| Total | 0 | 0 | 18 | 4 | 0 | 22 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001265355.2 | 12 | MANE Select | |
| Ensembl | ENSP00000511897.1 | 12 | MANE Select | |
| RefSeq | NP_001265356.2 | 12 | Standard | |
| RefSeq | NP_001265357.2 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Osteoclast differentiation - Homo sapiens (human)
- Immune System
- Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
- Adaptive Immune System
Biological Process
- adaptive immune response
- signal transduction
- positive regulation of regulatory T cell differentiation
- negative regulation of osteoclast differentiation
- negative regulation of T cell receptor signaling pathway
Molecular Function
- antigen binding
- protein binding
- signaling receptor activity
Cellular Component
- plasma membrane
- integral component of membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000391736
- Coding exons
- 12
- Length
- 26471
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125746
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.43 | 314 | 250 | 1.25 | 0.0000133 | 2843 |
| Missense (PolyPhen) | 46 | 42.633 | 1.079 | 541 | ||
| Synonymous | -1.19 | 116 | 101 | 1.15 | 0.00000570 | 910 |
| Loss of Function | 0.347 | 20 | 21.7 | 0.920 | 9.25e-7 | 252 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00021 | 0.00020 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000055 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C and HLA-G alleles. Involved in the down-regulation of the immune response and the development of tolerance, e.g. towards transplants. Interferes with TNFRSF5- signaling and NF-kappa-B up-regulation. Inhibits receptor-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions. {ECO:0000269|PubMed:11875462, ECO:0000269|PubMed:9151699}.;
Intolerance Scores
- LoFtool
- 0.991
- RVIS EVS
- 4.54
- RVIS percentile EVS
- 99.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.150
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |