PRAMEF13

Chr 1

PRAME family member 13

NCBI Gene: 400736 ENSG00000279169 UniProt: Q5VWM6

The protein functions as a ubiquitin-like ligase-substrate adaptor within the Cul2-RING ubiquitin ligase complex, facilitating proteasome-mediated protein degradation in the cytoplasm. PRAMEF13 mutations have not been definitively associated with human disease in the current literature. The gene shows moderate tolerance to loss-of-function variants (pLI = 0.29, LOEUF = 1.89), suggesting it may not be essential for normal development.

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 1.89

Clinical Summary— PRAMEF13

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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ClinVar Variants

2 VUS of 3 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.292

Z-score 0.30

OE 0.00 (0.00–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.81Z-score

OE missense 1.31 (1.08–1.59)

71 obs / 54.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.89)

0≤0.351.4

Missense OE?1.31 (1.08–1.59)

0≤0.61.4

Synonymous OE?0.67

0≤1.21.6

LoF obs/exp: 0 / 0.1Missense obs/exp: 71 / 54.2Syn Z: 1.28

This gene — mechanism propensity

0.7229th %ile

GOF

0.6346th %ile

LOF

0.2190th %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.

ClinVar Variant Classifications

3 submitted variants in ClinVar

ClinVar

Classification Summary

VUS2

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	2	0	2
Likely Benign	0	1	1
Benign	0	0	0
Total	2	1	3

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap PRAMEF13 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →