PRAMEF25

Chr 1

PRAME family member 25

NCBI Gene: 441873 ENSG00000229571 UniProt: A6NGN4

The 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. This gene appears to be unconstrained against loss-of-function variants in the general population (LOEUF 1.95), and no established human disease associations have been reported. Currently, there is insufficient evidence to support pathogenicity of variants in this gene for pediatric neurological conditions.

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…

DNmechanismLOEUF 1.95

Clinical Summary— PRAMEF25

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.95LOEUF

pLI 0.000

Z-score -1.43

OE 1.72 (0.91–1.95)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.35Z-score

OE missense 1.45 (1.24–1.71)

102 obs / 70.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.72 (0.91–1.95)

0≤0.351.4

Missense OE?1.45 (1.24–1.71)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 8 / 4.7Missense obs/exp: 102 / 70.2Syn Z: -1.21

This gene — mechanism propensity

0.79top 25%

GOF

0.6346th %ile

LOF

0.1697th %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.