PRAME

Chr 22

PRAME nuclear receptor transcriptional regulator

Also known as: CT130, MAPE, OIP-4, OIP4

NCBI Gene: 23532ENSG00000185686UniProt: P78395

This gene encodes an antigen that is preferentially expressed in human melanomas and that is recognized by cytolytic T lymphocytes. It is not expressed in normal tissues, except testis. The encoded protein acts as a repressor of retinoic acid receptor, and likely confers a growth advantage to cancer cells via this function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

210
ClinVar variants
83
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— PRAME
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
83 Pathogenic / Likely Pathogenic· 94 VUS of 210 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.25LOEUF
pLI 0.000
Z-score 0.85
OE 0.77 (0.49–1.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.87Z-score
OE missense 1.15 (1.04–1.26)
323 obs / 281.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.77 (0.49–1.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.15 (1.04–1.26)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 12 / 15.6Missense obs/exp: 323 / 281.9Syn Z: -1.17

ClinVar Variant Classifications

210 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic79
Likely Pathogenic4
VUS94
Likely Benign8
Benign6
79
Pathogenic
4
Likely Pathogenic
94
VUS
8
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
79
0
79
Likely Pathogenic
0
0
4
0
4
VUS
0
84
10
0
94
Likely Benign
0
8
0
0
8
Benign
0
2
2
2
6
Total094952191

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

View in ClinVar →

Protein Context — Lollipop Plot

PRAME · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PRAME Expression in Melanocytic Tumors.
Lezcano C et al.·Am J Surg Pathol
2018
Multi-omics analyses reveal biological and clinical insights in recurrent stage I non-small cell lung cancer.
Wang C et al.·Nat Commun
2025
Immunohistochemistry in melanocytic lesions: Updates with a practical review for pathologists.
Saleem A et al.·Semin Diagn Pathol
2022Review
Autologous T cell therapy for PRAME(+) advanced solid tumors in HLA-A*02(+) patients: a phase 1 trial.
Wermke M et al.·Nat Med
2025Clinical trial
Preferentially Expressed Antigen in Melanoma (PRAME) and the PRAME Family of Leucine-Rich Repeat Proteins.
Hermes N et al.·Curr Cancer Drug Targets
2016Review
Multi-omics comparison of malignant and normal uveal melanocytes reveals molecular features of uveal melanoma.
Gentien D et al.·Cell Rep
2023
Evaluation of PRAME immunohistochemistry in cutaneous vascular neoplasms reveals frequent expression in primary and post-irradiation cutaneous angiosarcomas.
Krajisnik A et al.·J Cutan Pathol
2024
Beyond Checkpoint Inhibition: Keeping Therapeutic Options Open.
Joshi UM et al.·Am Soc Clin Oncol Educ Book
2025Review
PRAME protein expression in DICER1-related tumours.
Thorner PS et al.·J Pathol Clin Res
2022
The Clinical, Morphologic, and Molecular Spectrum of BRAF Fusion Spitz Tumors.
Sharma N et al.·Am J Surg Pathol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Acute Myeloid LeukemiaMyelodysplastic Syndrome

Administration of Donor Multi TAA-Specific T Cells for AML or MDS (ADSPAM)

ACTIVE NOT RECRUITING
NCT02494167Phase PHASE1Baylor College of MedicineStarted 2016-02
MultiTAA-specific T cells
Hodgkin LymphomaNon-Hodgkin LymphomaHodgkin Disease

Administration of TAA-Specific CTLs; Hodgkin or Non-Hodgkin Lymphoma; TACTAL

ACTIVE NOT RECRUITING
NCT01333046Phase PHASE1Baylor College of MedicineStarted 2012-01
Antigen-Escalation StageDose-Escalation Stageazacytidine and multiTAA T cells Stage
Multiple Myeloma

Tumor-Associated Antigen-Specific Cytotoxic T-Lymphocytes for Multiple Myeloma

RECRUITING
NCT02291848Phase PHASE1Baylor College of MedicineStarted 2015-04
TAA-specific CTLsTAA-specific CTLs- fixed dose

External Resources

Links to major genomics databases and tools