PELI1

pellino E3 ubiquitin protein ligase 1, the group of Pellino E3 ubiquitin protein ligases

Basic information

Region (hg38): 2:64092651-64144420

Links

ENSG00000197329 ∙ NCBI:57162 ∙ OMIM:614797 ∙ HGNC:8827 ∙ Uniprot:Q96FA3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PELI1 gene.

• Inborn genetic diseases (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PELI1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			10			10
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	10	0	0

Variants in PELI1

This is a list of pathogenic ClinVar variants found in the PELI1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-64094742-T-C		not specified	Uncertain significance (Aug 13, 2021)
2-64094761-G-A		not specified	Uncertain significance (Aug 02, 2021)
2-64094890-C-T		not specified	Uncertain significance (Jan 09, 2024)
2-64095064-C-A		not specified	Uncertain significance (Oct 17, 2023)
2-64095070-T-G		not specified	Uncertain significance (Aug 04, 2023)
2-64095166-C-G		not specified	Uncertain significance (Feb 27, 2023)
2-64095171-G-A		not specified	Uncertain significance (Mar 06, 2023)
2-64095175-T-G		not specified	Uncertain significance (Sep 14, 2022)
2-64095177-T-C		not specified	Uncertain significance (Jan 27, 2022)
2-64095268-C-T		not specified	Uncertain significance (Dec 06, 2023)
2-64096231-T-C		not specified	Uncertain significance (Mar 14, 2023)
2-64096526-C-T		not specified	Uncertain significance (Dec 14, 2023)
2-64100454-G-A		not specified	Uncertain significance (Jun 02, 2023)
2-64100462-G-A		not specified	Uncertain significance (Feb 27, 2024)
2-64100496-T-C		not specified	Uncertain significance (Jan 26, 2022)
2-64104762-G-C		not specified	Uncertain significance (Aug 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PELI1	protein_coding	protein_coding	ENST00000358912	6	51803

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.390	0.609	125735	0	10	125745	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.12	149	242	0.617	0.0000132	2740
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000663	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;Interleukin-1 signaling;IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation;Innate Immune System;Immune System;IL1;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;MyD88 dependent cascade initiated on endosome;Toll Like Receptor 4 (TLR4) Cascade;IRAK1 recruits IKK complex;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.337
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.09

Haploinsufficiency Scores

• pHI: 0.864
• hipred: Y
• hipred_score: 0.775
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.976

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Peli1
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; digestive/alimentary phenotype

Gene ontology

• Biological process: protein polyubiquitination;positive regulation of cytokine production;protein phosphorylation;Toll signaling pathway;positive regulation of B cell proliferation;positive regulation of protein ubiquitination;negative regulation of NF-kappaB transcription factor activity;response to lipopolysaccharide;positive regulation of toll-like receptor 3 signaling pathway;positive regulation of toll-like receptor 4 signaling pathway;negative regulation of T cell proliferation;positive regulation of I-kappaB kinase/NF-kappaB signaling;proteasome-mediated ubiquitin-dependent protein catabolic process;response to dsRNA;negative regulation of necroptotic process;interleukin-1-mediated signaling pathway;protein K63-linked ubiquitination;protein K48-linked ubiquitination
• Cellular component: nucleus;cytosol
• Molecular function: protein serine/threonine kinase activity;protein binding;ubiquitin-ubiquitin ligase activity;ubiquitin protein ligase activity