PRAMEF2

Chr 1

PRAME family member 2

Also known as: DJ845O24.3

NCBI Gene: 65122 ENSG00000120952 UniProt: O60811 OMIM: 621664

The protein functions as a ubiquitin-like ligase-substrate adaptor in the Cul2-RING ubiquitin ligase complex, facilitating proteasome-mediated protein degradation in the cytoplasm. This gene is extremely tolerant to loss-of-function variants in the general population, suggesting that complete loss of function may not be pathogenic. No well-established human disease associations have been reported for PRAMEF2 mutations.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.81

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.81LOEUF

pLI 0.000

Z-score -0.64

OE 1.21 (0.78–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-3.95Z-score

OE missense 1.74 (1.60–1.89)

392 obs / 225.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.21 (0.78–1.81)

0≤0.351.4

Missense OE?1.74 (1.60–1.89)

0≤0.61.4

Synonymous OE?1.57

0≤1.21.6

LoF obs/exp: 13 / 10.7Missense obs/exp: 392 / 225.3Syn Z: -4.51

Background carrier burden — how many people carry a rare variant somewhere in PRAMEF2?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 37

630 rare PASS variants

Rare truncating (LoF)

1 in 1,300

60 rare PASS variants

Rare synonymous (reference)

1 in 120

266 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRAMEF2. 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)	~555k	1 in 48	1 in 1,900
South Asian	~43k	1 in 54	1 in 1,200
Remaining (unassigned)	~30k	1 in 33	1 in 1,200
European (Finnish)	~27k	1 in 71	≈ 1 in 27,000
Admixed American	~22k	1 in 51	1 in 1,200
African / African American	~21k	1 in 46	1 in 1,400
East Asian	~20k	1 in 44	1 in 730
Ashkenazi Jewish	~13k	1 in 110	none seen
Middle Eastern	~2,879	1 in 43	≈ 1 in 1,400

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 ↓