PRAME

protein-coding

PRAME nuclear receptor transcriptional regulator, the group of PRAME family

Gene summary

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]

Previous symbols:

MAPE

MANE transcript

NM_206956.3

Inheritance

—

ClinVar variants

U:92B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr22:22,547,701-22,559,361

External References & Databases

Ensembl (ENSG00000185686)

Transcript & Mutation Effects

hg38 • Region Span ~11.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRAME variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 94

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_206956.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		2 clinvar	3
missense			89 clinvar	8 clinvar	1 clinvar	98
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	92	8	3	103

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_206956.3	RefSeq	NP_996839.1	4	MANE Select
ENST00000405655.8	Ensembl	ENSP00000384343.3	4	MANE Select
NM_001291715.2	RefSeq	NP_001278644.1	4	Standard
NM_001291716.2	RefSeq	NP_001278645.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

apoptotic process
positive regulation of cell population proliferation
cell differentiation
regulation of growth
negative regulation of apoptotic process

Molecular Function

protein binding
retinoic acid receptor binding

Cellular Component

nucleus
cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000543184
Coding exons: 4
Length: 11646
Individuals with no LoFs: 125680
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125720
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.870	323	282	1.15	0.0000151	3314
Missense (PolyPhen)		58	56.331	1.0296		800
Synonymous	-1.17	135	119	1.14	0.00000657	1036
Loss of Function	0.846	12	15.6	0.769	0.00000102	149

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00046	0.00040	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00017	0.00016	rare
South Asian	0.00031	0.00029	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as a transcriptional repressor, inhibiting the signaling of retinoic acid through the retinoic acid receptors RARA, RARB and RARG. Prevents retinoic acid-induced cell proliferation arrest, differentiation and apoptosis. {ECO:0000269|PubMed:16179254}.;

Recessive Scores

pRec: 0.141

Intolerance Scores

LoFtool: 0.769
RVIS EVS: 0.27
RVIS percentile EVS: 70.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium