ERAP1

endoplasmic reticulum aminopeptidase 1, the group of Aminopeptidases|Minor histocompatibility antigens|M1 metallopeptidases

Basic information

Region (hg38): 5:96760810-96808100

Links

ENSG00000164307

∙ NCBI:51752 ∙ OMIM:606832 ∙ HGNC:18173 ∙ Uniprot:Q9NZ08 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ERAP1 gene.

not_specified (100 variants)
not_provided (28 variants)
Long_QT_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ERAP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001040458.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				9 clinvar	9 clinvar	18
missense			90 clinvar	11 clinvar	3 clinvar	104
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	91	20	12

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ERAP1	protein_coding	protein_coding	ENST00000296754	19	47283

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.06e-26	0.00253	124532	5	1211	125748	0.00485

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.529	470	503	0.934	0.0000256	6269
Missense in Polyphen		150	164.73	0.9106		2130
Synonymous	-0.0410	190	189	1.00	0.0000106	1779
Loss of Function	0.794	43	49.0	0.878	0.00000245	567

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0181	0.0182
Ashkenazi Jewish	0.0000999	0.0000992
East Asian	0.00761	0.00764
Finnish	0.00166	0.00166
European (Non-Finnish)	0.00390	0.00389
Middle Eastern	0.00761	0.00764
South Asian	0.00373	0.00363
Other	0.00391	0.00392

dbNSFP

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. Strongly prefers substrates 9-16 residues long. Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus, while it has weak activity toward peptides with charged C-terminus. May play a role in the inactivation of peptide hormones. May be involved in the regulation of blood pressure through the inactivation of angiotensin II and/or the generation of bradykinin in the kidney. {ECO:0000269|PubMed:15908954, ECO:0000269|PubMed:16286653, ECO:0000269|PubMed:21478864}.;

Recessive Scores

pRec: 0.116

Intolerance Scores

loftool: 0.999
rvis_EVS: 1.08
rvis_percentile_EVS: 91.73

Haploinsufficiency Scores

pHI: 0.107
hipred: N
hipred_score: 0.167
ghis: 0.467

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.517

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Erap1
Phenotype: immune system phenotype; renal/urinary system phenotype; hematopoietic system phenotype; endocrine/exocrine gland phenotype;

Gene ontology

Biological process: angiogenesis;adaptive immune response;antigen processing and presentation of peptide antigen via MHC class I;proteolysis;membrane protein ectodomain proteolysis;regulation of blood pressure;response to bacterium;antigen processing and presentation of endogenous peptide antigen via MHC class I;peptide catabolic process;regulation of innate immune response;fat cell differentiation;positive regulation of angiogenesis
Cellular component: extracellular region;extracellular space;cytoplasm;endoplasmic reticulum;endoplasmic reticulum lumen;endoplasmic reticulum membrane;cytosol;membrane;integral component of membrane;extracellular exosome
Molecular function: endopeptidase activity;aminopeptidase activity;interleukin-6 receptor binding;interleukin-1, type II receptor binding;protein binding;metalloexopeptidase activity;zinc ion binding;peptide binding;metalloaminopeptidase activity