PRAMEF33

Chr 1

PRAME family member 33

Also known as: PRAMEF33P

NCBI Gene: 645382 ENSG00000237700 UniProt: A0A0G2JMD5

The protein is predicted to function as a ubiquitin-like ligase-substrate adaptor within the Cul2-RING ubiquitin ligase complex, facilitating proteasome-mediated protein degradation in the cytoplasm. Currently, no established human diseases have been definitively linked to mutations in this gene. The clinical significance of PRAMEF33 variants in pediatric neurological conditions 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…

Multiplemechanism

Clinical Summary— PRAMEF33

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ClinVar Variants

4 total variants — no pathogenic classifications of 4 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.7325th %ile

GOF

0.6832th %ile

LOF

0.2091th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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.

ClinVar Variant Classifications

4 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Benign4

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Synonymous	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	0	0
Likely Benign	4	4
Benign	0	0
Total	4	4

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

16 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap PRAMEF33 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →