PELI3

Chr 11

pellino E3 ubiquitin protein ligase family member 3

NCBI Gene: 246330 ENSG00000174516 UniProt: Q8N2H9 OMIM: 609827

PELI3 encodes an E3 ubiquitin ligase that catalyzes ubiquitin attachment to substrate proteins and regulates innate immune signaling pathways including TLR, IL-1, and NOD1/NOD2 pathways through polyubiquitination of IRAK1 and RIPK2. The gene is moderately constrained against loss-of-function variants (LOEUF 0.658), but no established human disease associations have been reported for PELI3 mutations in the provided data.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.66

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.009

Z-score 2.69

OE 0.35 (0.20–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.43Z-score

OE missense 0.62 (0.55–0.70)

200 obs / 322.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.35 (0.20–0.66)

0≤0.351.4

Missense OE?0.62 (0.55–0.70)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 7 / 20.0Missense obs/exp: 200 / 322.6Syn Z: 0.77

Background carrier burden — how many people carry a rare variant somewhere in PELI3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

567 rare PASS variants

Rare truncating (LoF)

1 in 3,100

64 rare PASS variants

Rare synonymous (reference)

1 in 170

296 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PELI3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 4,800
South Asian	~43k	1 in 110	1 in 1,100
Remaining (unassigned)	~30k	1 in 130	≈ 1 in 10,000
European (Finnish)	~27k	1 in 440	≈ 1 in 21,000
Admixed American	~22k	1 in 83	≈ 1 in 6,900
African / African American	~21k	1 in 120	≈ 1 in 8,300
East Asian	~20k	1 in 130	1 in 480
Ashkenazi Jewish	~13k	1 in 650	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 7 coding exons well covered in gnomAD exomes; exon 3 poorly covered. Genomes: all 7.? see exons ↓