PRAMEF14

Chr 1

PRAME family member 14

NCBI Gene: 729528 ENSG00000204481 UniProt: Q5SWL7

This protein is predicted to function as a ubiquitin-like ligase-substrate adaptor in the Cul2-RING ubiquitin ligase complex, facilitating proteasome-mediated protein degradation in the cytoplasm. The gene shows tolerance to loss-of-function variants (LOEUF 1.89), and no established human disease associations have been reported for PRAMEF14 mutations. Clinical significance of variants in this gene remains to be determined.

ResearchSummary from RefSeq

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be part of Cul2-RING ubiquitin ligase complex. Predicted to be active in cytoplasm. [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

1.89

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.290

Z-score 0.28

OE 0.00 (0.00–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.60Z-score

OE missense 1.19 (1.01–1.42)

92 obs / 77.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.89)

0≤0.351.4

Missense OE?1.19 (1.01–1.42)

0≤0.61.4

Synonymous OE?1.46

0≤1.21.6

LoF obs/exp: 0 / 0.1Missense obs/exp: 92 / 77.2Syn Z: -2.09

Background carrier burden — how many people carry a rare variant somewhere in PRAMEF14?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 60

549 rare PASS variants

Rare truncating (LoF)

1 in 480

50 rare PASS variants

Rare synonymous (reference)

1 in 83

225 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRAMEF14. 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 92	1 in 2,300
South Asian	~43k	1 in 57	1 in 710
Remaining (unassigned)	~30k	1 in 64	1 in 700
European (Finnish)	~27k	1 in 260	1 in 1,700
Admixed American	~22k	1 in 70	1 in 730
African / African American	~21k	1 in 45	1 in 500
East Asian	~20k	1 in 56	1 in 2,700
Ashkenazi Jewish	~13k	1 in 930	none seen
Middle Eastern	~2,874	1 in 55	≈ 1 in 2,900

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): 3 of 3 coding exons well covered in gnomAD exomes. Genomes: 1 of 3 (exons 2, 4 below).? see exons ↓