YPEL4

Chr 11

yippee like 4

NCBI Gene: 219539 ENSG00000166793 UniProt: Q96NS1 OMIM: 609725

Predicted to enable metal ion binding activity. Predicted to act upstream of or within several processes, including negative regulation of erythrocyte clearance; negative regulation of erythrocyte differentiation; and protein localization to plasma membrane. Predicted to be located in nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.94

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.196

Z-score 1.69

OE 0.30 (0.12–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.33Z-score

OE missense 0.55 (0.42–0.72)

38 obs / 69.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.12–0.94)

0≤0.351.4

Missense OE?0.55 (0.42–0.72)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 2 / 6.7Missense obs/exp: 38 / 69.0Syn Z: 0.76

Background carrier burden — how many people carry a rare variant somewhere in YPEL4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 540

174 rare PASS variants

Rare truncating (LoF)

1 in 9,800

25 rare PASS variants

Rare synonymous (reference)

1 in 580

91 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for YPEL4. 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 1,000	1 in 11,000
South Asian	~43k	1 in 460	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 290	≈ 1 in 9,800
European (Finnish)	~27k	1 in 1,100	≈ 1 in 27,000
Admixed American	~22k	1 in 590	none seen
African / African American	~21k	1 in 290	1 in 3,000
East Asian	~20k	1 in 790	≈ 1 in 17,000
Ashkenazi Jewish	~13k	≈ 1 in 4,300	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 450	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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓