PELI3
protein-codingpellino E3 ubiquitin protein ligase family member 3, the group of Pellino E3 ubiquitin protein ligases
Gene summary
The protein encoded by this gene is a scaffold protein and an intermediate signaling protein in the innate immune response pathway. The encoded protein helps transmit the immune response signal from Toll-like receptors to IRAK1/TRAF6 complexes. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.0 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 PELI3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_145065.3. 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 | 2 | 2 | ||||
| missense | 53 | 53 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 56 | 0 | 0 | 56 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_659502.2 | 7 | MANE Select | |
| Ensembl | ENSP00000322532.7 | 7 | MANE Select | |
| RefSeq | NP_001091980.1 | 6 | Standard | |
| RefSeq | NP_001230064.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of toll-like receptor signaling pathway
- Toll Like Receptor 7/8 (TLR7/8) Cascade
- Signaling by Interleukins
- Cytokine Signaling in Immune system
- Toll Like Receptor 9 (TLR9) Cascade
Biological Process
- protein polyubiquitination
- protein phosphorylation
- Toll signaling pathway
- negative regulation of tumor necrosis factor-mediated signaling pathway
- interleukin-1-mediated signaling pathway
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ubiquitin protein ligase activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000320740
- Coding exons
- 7
- Length
- 10593
- Individuals with no LoFs
- 125724
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 24
- Defined
- 125748
- p
- 0.0000954
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.43 | 200 | 323 | 0.620 | 0.0000226 | 2968 |
| Missense (PolyPhen) | 107 | 184.25 | 0.58074 | 1722 | ||
| Synonymous | 0.769 | 132 | 144 | 0.918 | 0.0000106 | 1023 |
| Loss of Function | 2.69 | 7 | 20.0 | 0.350 | 0.00000110 | 203 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00023 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000057 | 0.000053 | rare |
| South Asian | 0.00037 | 0.00036 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates 'Lys-63'-linked polyubiquitination of IRAK1. Can activate AP1/JUN and ELK1. Not required for NF-kappa-B activation. {ECO:0000269|PubMed:12874243, ECO:0000269|PubMed:17675297}.;
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- LoFtool
- 0.525
- RVIS EVS
- 0
- RVIS percentile EVS
- 53.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.675
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |