ERAP2

Chr 5

endoplasmic reticulum aminopeptidase 2

Also known as: L-RAP, LRAP

NCBI Gene: 64167ENSG00000164308UniProt: Q6P179

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]

156
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ERAP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 118 VUS of 156 total submissions

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.
1.19LOEUF
pLI 0.000
Z-score 0.46
OE 0.93 (0.73–1.19)
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.
-0.07Z-score
OE missense 1.01 (0.94–1.09)
501 obs / 496.5 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.0.93 (0.73–1.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.94–1.09)
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.0.99
0≤1.21.6
LoF obs/exp: 45 / 48.5Missense obs/exp: 501 / 496.5Syn Z: 0.15

ClinVar Variant Classifications

156 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS118
Likely Benign10
Benign6
20
Pathogenic
2
Likely Pathogenic
118
VUS
10
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
2
0
2
VUS
0
109
9
0
118
Likely Benign
0
6
2
2
10
Benign
1
2
1
2
6
Total1117344156

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

View in ClinVar →

Protein Context — Lollipop Plot

ERAP2 · 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
Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis.
Kuiper JJW et al.·Hum Mol Genet
2018Meta-analysis
ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19?
D'Amico S et al.·Int J Mol Sci
2021Review
Molecular and pathogenic effects of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in MHC-I-associated inflammatory disorders: Towards a unifying view.
López de Castro JA et al.·Mol Immunol
2016Review
The Impact of the 'Mis-Peptidome' on HLA Class I-Mediated Diseases: Contribution of ERAP1 and ERAP2 and Effects on the Immune Response.
Tedeschi V et al.·Int J Mol Sci
2020Review
EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders.
Kuiper JJ et al.·Ann Rheum Dis
2023Review
Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis.
Marusina AI et al.·J Invest Dermatol
2023
ERAP1 and ERAP2 gene variants as potential clinical biomarkers of anti-interleukin-17A response in psoriasis vulgaris.
Kronborg L et al.·Clin Exp Dermatol
2024
Identifying and validating immunological biomarkers in obstructive sleep apnea through bioinformatics analysis.
Zhou EH et al.·Sci Rep
2025
Genetic association of ERAP1 and ERAP2 with eclampsia and preeclampsia in northeastern Brazilian women.
Ferreira LC et al.·Sci Rep
2021
ERAP2 Is Associated With Immune Infiltration and Predicts Favorable Prognosis in SqCLC.
Yang Z et al.·Front Immunol
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
ERAP2 inhibitor -incorporated nanofibers: Characterization and biological assessment.
Vasconcelos F et al.·Int J Pharm
2026
The Impact of ERAP1 and ERAP2 Haplotype Combinations on Susceptibility and Severity of Birdshot Chorioretinitis.
Loeliger J et al.·Invest Ophthalmol Vis Sci
2026🔓 Open Access
Expression, Purification, and Functional Analysis Methods of Antigen-Processing Aminopeptidases ERAP1, ERAP2, and IRAP.
Mpakali A.·Methods Mol Biol
2026Functional
Exploring the genetic interaction between ERAP1/ERAP2 and HLA-B*52:01 in Takayasu arteritis.
Casares-Marfil D et al.·Rheumatology (Oxford)
2026
Rare and common variants in ERAP1 and ERAP2 selected for in response to Yersinia pestis infection contribute to autoimmune disease including inflammatory bowel disease.
Win LK et al.·Mamm Genome
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools