ERAP1

Chr 5

endoplasmic reticulum aminopeptidase 1

Also known as: A-LAP, ALAP, APPILS, ARTS-1, ARTS1, ERAAP, ERAAP1, PILS-AP

NCBI Gene: 51752ENSG00000164307UniProt: Q9NZ08

The protein encoded by this gene is an aminopeptidase involved in trimming HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin II. Three transcript variants encoding two different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

393
ClinVar variants
27
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ERAP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 241 VUS of 393 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.
1.13LOEUF
pLI 0.000
Z-score 0.79
OE 0.88 (0.69–1.13)
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.
0.53Z-score
OE missense 0.93 (0.86–1.01)
470 obs / 503.4 exp
Tolerant

Mild missense constraint

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.0.88 (0.69–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.86–1.01)
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.1.00
0≤1.21.6
LoF obs/exp: 43 / 49.0Missense obs/exp: 470 / 503.4Syn Z: -0.04

ClinVar Variant Classifications

393 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic3
VUS241
Likely Benign42
Benign82
Conflicting1
24
Pathogenic
3
Likely Pathogenic
241
VUS
42
Likely Benign
82
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
22
0
24
Likely Pathogenic
0
0
3
0
3
VUS
1
232
8
0
241
Likely Benign
0
17
8
17
42
Benign
1
16
48
17
82
Conflicting
—1
Total42658934393

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

View in ClinVar →

Protein Context — Lollipop Plot

ERAP1 · 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
Understanding the Pathogenesis of Spondyloarthritis.
Sharip A et al.·Biomolecules
2020Review
An observational and genetic investigation into the association between psoriasis and risk of malignancy.
Li R et al.·Nat Commun
2024
ERAP1 and ankylosing spondylitis.
Keidel S et al.·Curr Opin Immunol
2013Review
Structural and biochemical insights into the association between ERAP1 polymorphism and autoimmune diseases.
Liu S et al.·Biochem Biophys Res Commun
2022Review
The role of polymorphic ERAP1 in autoinflammatory disease.
Reeves E et al.·Biosci Rep
2018Review
Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis.
Kuiper JJW et al.·Hum Mol Genet
2018Meta-analysis
Genetics of psoriatic arthritis.
O'Rielly DD et al.·Best Pract Res Clin Rheumatol
2014Review
EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders.
Kuiper JJ et al.·Ann Rheum Dis
2023Review
ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19?
D'Amico S et al.·Int J Mol Sci
2021Review
Epistasis of ERAP1 With 4 Major Histocompatibility Complex Class I Alleles in Frontal Fibrosing Alopecia: A Genome-Wide Association Study Meta-Analysis.
Rayinda T et al.·JAMA Dermatol
2025Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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
Utility of serum ERAP1 and ERAP2 as novel biomarkers in the management of recalcitrant warts: A cross-sectional study.
Younis I et al.·Indian J Dermatol Venereol Leprol
2025
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