PRAMEF2

protein-coding

PRAME family member 2, the group of PRAME family

Gene summary

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]

MANE transcript

NM_023014.1

Inheritance

—

ClinVar variants

U:103B:33

Top phenotype

Bladder exstrophy-epispadias-cloacal exstrophy complex

gnomAD constraint

pLI —, LoF o/e 1.21

Max pathogenic AF

—

Genomic locus

chr1:12,857,086-12,861,909

External References & Databases

Ensembl (ENSG00000120952)

Transcript & Mutation Effects

hg38 • Region Span ~4.8 kb

Loading mutation effect viewer...

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 PRAMEF2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 111

not providedTotal: 32

Bladder exstrophy-epispadias-cloacal exstrophy complexTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_023014.1. 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				15 clinvar		15
missense			103 clinvar	17 clinvar		120
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	103	33	0	136

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_023014.1	RefSeq	NP_075390.1	3	MANE Select
ENST00000240189.2	Ensembl	ENSP00000240189.2	3	MANE Select
XM_011542004.1	RefSeq	XP_011540306.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of cell population proliferation
negative regulation of apoptotic process
negative regulation of cell differentiation
negative regulation of transcription, DNA-templated

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000240189
Coding exons: 3
Length: 4824
Individuals with no LoFs: 110879
Homozygous LoFs: 248
Heterozygous LoFs: 14250
Defined: 125377
p: 0.0596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-3.95	392	225	1.74	0.0000117	3003
Missense (PolyPhen)		87	60.158	1.4462		915
Synonymous	-4.51	158	100	1.57	0.00000570	906
Loss of Function	-0.645	13	10.7	1.21	4.72e-7	140

Population LoF Frequency

Population	CAF	p-value	Status
African	0.026	0.022	notable
Latino/Admixed American	0.028	0.026	notable
Ashkenazi Jewish	0.028	0.028	notable
East Asian	0.24	0.27	notable
Finnish	0.072	0.074	notable
European (Non-Finnish)	0.048	0.048	notable
South Asian	0.053	0.054	notable
Other	0.051	0.051	notable

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.932
RVIS EVS: 5.21
RVIS percentile EVS: 99.84

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0295

Gene Damage Prediction

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