PELI1
protein-codingpellino E3 ubiquitin protein ligase 1, the group of Pellino E3 ubiquitin protein ligases
Gene summary
Enables ubiquitin-ubiquitin ligase activity. Involved in several processes, including negative regulation of TORC1 signaling; negative regulation of necroptotic process; and protein polyubiquitination. Located in nucleolus and nucleoplasm. Is active in site of double-strand break. Implicated in colorectal cancer. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~51.8 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 PELI1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020651.4. 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 | 2 | 1 | 3 | |||
| missense | 46 | 46 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 52 | 1 | 0 | 53 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065702.2 | 6 | MANE Select | |
| Ensembl | ENSP00000351789.4 | 6 | MANE Select | |
| Ensembl | ENSP00000573287.1 | 7 | Standard | |
| Ensembl | ENSP00000573287.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of toll-like receptor signaling pathway
- IL-1 signaling pathway
- Toll Like Receptor 7/8 (TLR7/8) Cascade
- Signaling by Interleukins
- Cytokine Signaling in Immune system
Biological Process
- protein polyubiquitination
- positive regulation of cytokine production
- protein phosphorylation
- Toll signaling pathway
- positive regulation of B cell proliferation
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ubiquitin-ubiquitin ligase activity
- ubiquitin protein ligase activity
Cellular Component
- nucleus
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358912
- Coding exons
- 6
- Length
- 51803
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125745
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.12 | 149 | 242 | 0.617 | 0.0000132 | 2740 |
| Missense (PolyPhen) | 44 | 99.222 | 0.44345 | 1061 | ||
| Synonymous | -1.06 | 98 | 85.6 | 1.15 | 0.00000484 | 811 |
| Loss of Function | 3.06 | 4 | 18.0 | 0.222 | 8.61e-7 | 223 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
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 allowing subsequent NF-kappa-B activation (PubMed:12496252, PubMed:17675297). Mediates 'Lys-48'- linked polyubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation; preferentially recognizes and mediates the degradation of the 'Thr-182' phosphorylated form of RIPK3 (PubMed:29883609). Negatively regulates necroptosis by reducing RIPK3 expression (PubMed:29883609). Mediates 'Lys-63'- linked ubiquitination of RIPK1 (PubMed:29883609). {ECO:0000269|PubMed:12496252, ECO:0000269|PubMed:17675297, ECO:0000269|PubMed:29883609}.;
Recessive Scores
- pRec
- 0.128
Intolerance Scores
- LoFtool
- 0.337
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.976
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |