LILRA4
protein-codingleukocyte immunoglobulin like receptor A4, the group of CD molecules|Activating leukocyte immunoglobulin like receptors
Gene summary
This gene encodes an immunoglobulin-like cell surface protein that is expressed predominantly on plasmacytoid dendritic cells (PDCs) and modulates the function of these cells in the immune response. Expression of this gene is downregulated by interleukin 3 (IL3). This gene is one of a cluster of highly related genes located at chromosomal region 19q13.4. [provided by RefSeq, Jan 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.0 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 LILRA4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012276.5. 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 | 84 | 11 | 95 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 85 | 12 | 0 | 97 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036408.4 | 8 | MANE Select | |
| Ensembl | ENSP00000291759.4 | 8 | MANE Select | |
| Ensembl | ENSP00000471722.1 | 2 | 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
- negative regulation of interferon-alpha production
- negative regulation of tumor necrosis factor production
- negative regulation of toll-like receptor 7 signaling pathway
- negative regulation of toll-like receptor 9 signaling pathway
- Fc-epsilon receptor signaling pathway
Molecular Function
- signaling receptor binding
- protein binding
- coreceptor activity
Cellular Component
- integral component of plasma membrane
- Fc-epsilon receptor I complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000291759
- Coding exons
- 8
- Length
- 5966
- Individuals with no LoFs
- 125698
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 22
- Defined
- 125721
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.498 | 314 | 290 | 1.08 | 0.0000167 | 3162 |
| Missense (PolyPhen) | 64 | 79.097 | 0.80913 | 960 | ||
| Synonymous | -1.25 | 147 | 129 | 1.14 | 0.00000798 | 1042 |
| Loss of Function | -0.0984 | 23 | 22.5 | 1.02 | 0.00000105 | 246 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00087 | 0.00082 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions coreceptor to limit the innate immune responses to viral infections; signaling occurs via FCER1G (PubMed:16735691, PubMed:19564354). Down-regulates the production of IFNA1, IFNA2, IFNA4, IFNB1 and TNF by plasmacytoid dendritic cells that have been exposed to influenza virus or cytidine- phosphate-guanosine (CpG) dinucleotides, indicating it functions as negative regulator of TLR7 and TLR9 signaling cascades (PubMed:16735691, PubMed:19564354, PubMed:24586760). Down- regulates interferon production in response to interaction with BST2 on HIV-1 infected cells (PubMed:26172439). Activates a signaling cascade in complex with FCER1G that results in phosphorylation of Src family and Syk kinases and thereby triggers mobilization of intracellular Ca(2+) (PubMed:16735691, PubMed:19564354). Does not interfere with the differentiation of plasmacytoid dendritic cells into antigen-presenting cells (PubMed:24586760). {ECO:0000269|PubMed:16735691, ECO:0000269|PubMed:19564354, ECO:0000269|PubMed:24586760, ECO:0000269|PubMed:26172439}.;
Recessive Scores
- pRec
- 0.0944
Intolerance Scores
- LoFtool
- 0.905
- RVIS EVS
- 0.54
- RVIS percentile EVS
- 81.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.121
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |