ERAP2

protein-coding

endoplasmic reticulum aminopeptidase 2, the group of Aminopeptidases|M1 metallopeptidases

Gene summary

This gene encodes a zinc metalloaminopeptidase of the M1 protease family that resides in the endoplasmic reticulum and functions in N-terminal trimming antigenic epitopes for presentation by major histocompatibility complex (MHC) class I molecules. Certain mutations in this gene are associated with the inflammatory arthritis syndrome ankylosing spondylitis and pre-eclampsia. This gene is located adjacent to a closely related aminopeptidase gene on chromosome 5. [provided by RefSeq, Jul 2016]

MANE transcript

NM_022350.5

Inheritance

—

ClinVar variants

U:123B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr5:96,875,986-96,919,703

External References & Databases

Ensembl (ENSG00000164308)

Transcript & Mutation Effects

hg38 • Region Span ~43.7 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 ERAP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 114

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022350.5. 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	2 clinvar	5
missense			111 clinvar	6 clinvar	2 clinvar	119
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	123	8	4	135

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022350.5	RefSeq	NP_071745.1	18	MANE Select
ENST00000437043.8	Ensembl	ENSP00000400376.3	18	MANE Select
NM_001130140.3	RefSeq	NP_001123612.1	18	Standard
NM_001329229.2	RefSeq	NP_001316158.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

adaptive immune response
antigen processing and presentation of peptide antigen via MHC class I
proteolysis
regulation of blood pressure
antigen processing and presentation of endogenous peptide antigen via MHC class I

Molecular Function

endopeptidase activity
aminopeptidase activity
metallopeptidase activity
zinc ion binding
peptide binding

Cellular Component

cytoplasm
endoplasmic reticulum lumen
endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000437043
Coding exons: 18
Length: 43778
Individuals with no LoFs: 125299
Homozygous LoFs: 2
Heterozygous LoFs: 447
Defined: 125748
p: 0.00179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0715	501	497	1.01	0.0000243	6323
Missense (PolyPhen)		189	169.17	1.1172		2287
Synonymous	0.150	183	186	0.986	0.00000970	1782
Loss of Function	0.461	45	48.5	0.929	0.00000233	608

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0024	0.0024	notable
Latino/Admixed American	0.0011	0.0010	notable
Ashkenazi Jewish	0.0035	0.0035	notable
East Asian	0.0023	0.0022	notable
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.0019	0.0018	notable
South Asian	0.0025	0.0024	notable
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I- binding peptides. Peptide trimming is essential to customize longer precursor peptides to fit them to the correct length required for presentation on MHC class I molecules. Preferentially hydrolyzes the basic residues Arg and Lys. {ECO:0000269|PubMed:12799365, ECO:0000269|PubMed:15908954, ECO:0000269|PubMed:16286653}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.995
RVIS EVS: 0.39
RVIS percentile EVS: 75.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.233

Gene Damage Prediction

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