PELI2

protein-coding

pellino E3 ubiquitin protein ligase family member 2, the group of Pellino E3 ubiquitin protein ligases

Gene summary

Predicted to enable protein-macromolecule adaptor activity and ubiquitin protein ligase activity. Acts upstream of or within positive regulation of MAPK cascade and positive regulation of protein phosphorylation. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_021255.3

Inheritance

—

ClinVar variants

U:51B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr14:56,117,814-56,301,524

External References & Databases

Ensembl (ENSG00000139946)

Transcript & Mutation Effects

hg38 • Region Span ~183.7 kb

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GenCC 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 PELI2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021255.3. 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 clinvar	1 clinvar	3
missense			51 clinvar		1 clinvar	52
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	51	2	2	55

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021255.3	RefSeq	NP_067078.1	6	MANE Select
ENST00000267460.9	Ensembl	ENSP00000267460.4	6	MANE Select
ENST00000559044.5	Ensembl	ENSP00000452666.1	3	Standard
ENST00000561019.1	Ensembl	ENSP00000453988.1	3	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 protein phosphorylation
protein phosphorylation
Toll signaling pathway
positive regulation of I-kappaB kinase/NF-kappaB signaling

Molecular Function

protein serine/threonine kinase activity
protein binding
ubiquitin-ubiquitin ligase activity
ubiquitin protein ligase activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000267460
Coding exons: 6
Length: 183713
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125738
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	186	258	0.720	0.0000154	2747
Missense (PolyPhen)		67	118.44	0.56567		1212
Synonymous	-1.21	122	106	1.15	0.00000758	819
Loss of Function	3.40	3	19.0	0.158	0.00000108	203

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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 IL1B-induced IRAK1 'Lys-63'-linked polyubiquitination and possibly 'Lys-48'-linked ubiquitination. May be important for LPS- and IL1B-induced MAP3K7- dependent, but not MAP3K3-dependent, NF-kappa-B activation. Can activate the MAP (mitogen activated protein) kinase pathway leading to activation of ELK1. {ECO:0000269|PubMed:12804775, ECO:0000269|PubMed:12860405, ECO:0000269|PubMed:17675297, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:22669975}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.0525
RVIS EVS: -0.6
RVIS percentile EVS: 18.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.673

Gene Damage Prediction

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