LY96
protein-codinglymphocyte antigen 96, the group of MD-2 related lipid recognition domain containing
Gene summary
This gene encodes a protein which associates with toll-like receptor 4 on the cell surface and confers responsiveness to lipopolysaccyaride (LPS), thus providing a link between the receptor and LPS signaling. Studies of the mouse ortholog suggest that this gene may be involved in endotoxin neutralization. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~37.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0003778
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LY96 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015364.5. 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 | 0 | |||||
| missense | 11 | 2 | 13 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 16 | 2 | 0 | 18 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056179.4 | 5 | MANE Select | |
| Ensembl | ENSP00000284818.2 | 5 | MANE Select | |
| RefSeq | NP_001182726.1 | 4 | Standard | |
| Ensembl | ENSP00000430533.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pertussis - Homo sapiens (human)
- Toll-like receptor signaling pathway - Homo sapiens (human)
- Toxoplasmosis - Homo sapiens (human)
- Pathogenic Escherichia coli infection - Homo sapiens (human)
- NF-kappa B signaling pathway - Homo sapiens (human)
Biological Process
- toll-like receptor signaling pathway
- MyD88-dependent toll-like receptor signaling pathway
- MyD88-independent toll-like receptor signaling pathway
- inflammatory response
- cellular defense response
Molecular Function
- lipopolysaccharide binding
- lipopolysaccharide receptor activity
- protein binding
- coreceptor activity
- Toll-like receptor 4 binding
Cellular Component
- extracellular space
- plasma membrane
- endosome membrane
- intrinsic component of plasma membrane
- lipopolysaccharide receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000284818
- Coding exons
- 5
- Length
- 37736
- Individuals with no LoFs
- 125711
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 28
- Defined
- 125739
- p
- 0.000111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.148 | 77 | 80.8 | 0.954 | 0.00000380 | 1046 |
| Missense (PolyPhen) | 25 | 30.607 | 0.81681 | 397 | ||
| Synonymous | 0.719 | 24 | 28.9 | 0.830 | 0.00000143 | 281 |
| Loss of Function | 0.535 | 7 | 8.70 | 0.804 | 4.50e-7 | 110 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0.00039 | 0.00039 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds bacterial lipopolysaccharide (LPS) (PubMed:17803912, PubMed:17569869). Cooperates with TLR4 in the innate immune response to bacterial lipopolysaccharide (LPS), and with TLR2 in the response to cell wall components from Gram- positive and Gram-negative bacteria (PubMed:11160242, PubMed:11593030). Enhances TLR4-dependent activation of NF-kappa-B (PubMed:10359581). Cells expressing both LY96 and TLR4, but not TLR4 alone, respond to LPS (PubMed:10359581). {ECO:0000269|PubMed:10359581, ECO:0000269|PubMed:11160242, ECO:0000269|PubMed:11593030, ECO:0000269|PubMed:17569869, ECO:0000269|PubMed:17803912}.;
Recessive Scores
- pRec
- 0.177
Intolerance Scores
- RVIS EVS
- 0.46
- RVIS percentile EVS
- 78.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |