ERAP1

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

Basic information

Region (hg38): 5:96760809-96808100

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 provided (64 variants)
• not specified (36 variants)
• Inborn genetic diseases (36 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	15	22
missense			27	5	12	44
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding			8	8	49	65
Total	0	0	35	20	76

Variants in ERAP1

This is a list of pathogenic ClinVar variants found in the ERAP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-96762144-T-C			Benign (Nov 10, 2018)
5-96762191-T-G			Benign (Nov 10, 2018)
5-96762275-A-G		CAST-related disorder	Benign (Nov 27, 2023)
5-96762277-T-C		Inborn genetic diseases	Uncertain significance (Jun 29, 2022)
5-96762292-C-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
5-96762299-C-T			Benign (Jan 25, 2024)
5-96762312-AG-A		Peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome	Pathogenic (Mar 05, 2015)
5-96762338-C-T			Uncertain significance (Aug 10, 2023)
5-96762361-C-T		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
5-96762440-G-A			Benign (Jun 19, 2021)
5-96762510-G-A			Benign (Nov 10, 2018)
5-96765060-G-C			Benign (Nov 10, 2018)
5-96765218-C-T		ERAP1-related disorder	Benign (Jun 24, 2023)
5-96765225-G-A			Likely benign (Sep 07, 2022)
5-96765237-T-C		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
5-96765244-T-C			Likely benign (Feb 01, 2024)
5-96765315-ATAAAG-A			Pathogenic (Nov 22, 2023)
5-96765320-G-C		Inborn genetic diseases	Uncertain significance (Apr 28, 2023)
5-96765327-TAA-T			Benign (Jun 09, 2021)
5-96765327-TAAA-T		not specified	Benign (Jun 09, 2021)
5-96765327-TAAAAAAAAAAAAAAA-T			Likely benign (Jan 04, 2023)
5-96765331-A-AAAAAAAAAAAAAAAAAAAAAAT			Likely benign (Oct 11, 2023)
5-96765340-A-G			Benign (Nov 28, 2023)
5-96765362-T-TA			Benign (Nov 10, 2018)
5-96765516-A-G			Benign (Nov 10, 2018)

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