PRAMEF15

Chr 1

PRAME family member 15

NCBI Gene: 653619 ENSG00000204501 UniProt: P0DUQ1

The protein functions as a ubiquitin-like ligase-substrate adaptor within the Cul2-RING ubiquitin ligase complex, facilitating proteasome-mediated protein degradation. The gene shows low constraint against loss-of-function variants (pLI 0.33, LOEUF 1.84), and no established Mendelian disease associations have been reported to date.

ResearchSummary from RefSeq

Enables ubiquitin-like ligase-substrate adaptor activity. Involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Is active in Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

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

1.84

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.84LOEUF

pLI 0.329

Z-score 0.62

OE 0.00 (0.00–1.84)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.07Z-score

OE missense 0.89 (0.39–1.81)

3 obs / 3.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.84)

0≤0.351.4

Missense OE?0.89 (0.39–1.81)

0≤0.61.4

Synonymous OE?1.77

0≤1.21.6

LoF obs/exp: 0 / 0.4Missense obs/exp: 3 / 3.4Syn Z: -0.64

Background carrier burden — how many people carry a rare variant somewhere in PRAMEF15?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 43

499 rare PASS variants

Rare truncating (LoF)

1 in 810

50 rare PASS variants

Rare synonymous (reference)

1 in 83

178 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRAMEF15. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

Exome coverage (gnomAD): 3 of 3 coding exons well covered in gnomAD exomes. Genomes: 2 of 3 (exon 4 below).? see exons ↓