YPEL3

Chr 16

yippee like 3

NCBI Gene: 83719 ENSG00000090238 UniProt: P61236 OMIM: 609724

YPEL3 encodes a protein that binds metal ions and is involved in regulating cellular senescence and proliferation/apoptosis in myeloid precursor cells. Mutations in YPEL3 have not been definitively associated with human disease. The gene shows tolerance to loss-of-function variation (pLI 0.04, LOEUF 1.15).

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable metal ion binding activity. Involved in positive regulation of cellular senescence. Predicted to be located in nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.15

Clinical Summary— YPEL3

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Population Constraint (gnomAD)

Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 10 VUS of 17 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.042

Z-score 1.32

OE 0.45 (0.20–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.54Z-score

OE missense 0.57 (0.46–0.71)

59 obs / 103.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.20–1.15)

0≤0.351.4

Missense OE?0.57 (0.46–0.71)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 3 / 6.7Missense obs/exp: 59 / 103.0Syn Z: 0.12

This gene — mechanism propensity

0.6453th %ile

GOF

0.5954th %ile

LOF

0.3939th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

17 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS10

Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	1	0	1
Likely Pathogenic	0	0	0
VUS	0	10	10
Likely Benign	0	0	0
Benign	0	0	0
Total	1	10	11

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

282 pathogenic / likely-pathogenic (of 302) ClinVar copy-number / structural variants overlap YPEL3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →