ANPEP

protein-coding

alanyl aminopeptidase, membrane, the group of CD molecules|Aminopeptidases|M1 metallopeptidases

Gene summary

Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Its function in proximal tubular epithelial cells and other cell types is less clear. The large extracellular carboxyterminal domain contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with known enzymes of this class showed that CD13 and aminopeptidase N are identical. The latter enzyme was thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the CNS. This membrane-bound zinc metalloprotease is known to serve as a receptor for the HCoV-229E alphacoronavirus as well as other non-human coronaviruses. This gene has also been shown to promote angiogenesis, tumor growth, and metastasis and defects in this gene are associated with various types of leukemia and lymphoma. [provided by RefSeq, Apr 2020]

Previous symbols:

CD13
PEPN

MANE transcript

NM_001150.3

Inheritance

—

ClinVar variants

U:122B:22

Top phenotype

ANPEP-related disorder

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr15:89,784,895-89,815,401

External References & Databases

Ensembl (ENSG00000166825)

Transcript & Mutation Effects

hg38 • Region Span ~30.5 kb

Loading mutation effect viewer...

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 ANPEP variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 121

not providedTotal: 17

ANPEP-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001150.3. 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			3 clinvar	6 clinvar	4 clinvar	13
missense			117 clinvar	12 clinvar		129
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	122	18	4	144

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001150.3	RefSeq	NP_001141.2	20	MANE Select
ENST00000300060.7	Ensembl	ENSP00000300060.6	20	MANE Select
NM_001381923.1	RefSeq	NP_001368852.1	20	Standard
NM_001381924.1	RefSeq	NP_001368853.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Renin-angiotensin system - Homo sapiens (human)
Glutathione metabolism - Homo sapiens (human)
Hematopoietic cell lineage - Homo sapiens (human)
Gamma-glutamyl-transpeptidase deficiency
5-oxoprolinase deficiency

Biological Process

angiogenesis
proteolysis
cell differentiation
peptide catabolic process
neutrophil degranulation

Molecular Function

virus receptor activity
aminopeptidase activity
metallopeptidase activity
zinc ion binding
signaling receptor activity

Cellular Component

extracellular space
cytoplasm
lysosomal membrane
endoplasmic reticulum-Golgi intermediate compartment
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300060
Coding exons: 20
Length: 30514
Individuals with no LoFs: 125666
Homozygous LoFs: 0
Heterozygous LoFs: 82
Defined: 125748
p: 0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.43	492	590	0.834	0.0000373	6362
Missense (PolyPhen)		89	146.68	0.60675		1612
Synonymous	-1.43	290	261	1.11	0.0000188	1886
Loss of Function	3.64	23	51.1	0.450	0.00000260	533

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00027	0.00027	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00043	0.00043	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Broad specificity aminopeptidase which plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Also involved in the processing of various peptides including peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines. May also be involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells. May have a role in angiogenesis and promote cholesterol crystallization. {ECO:0000269|PubMed:10605003, ECO:0000269|PubMed:10676659, ECO:0000269|PubMed:11384645, ECO:0000269|PubMed:12473585, ECO:0000269|PubMed:7576235, ECO:0000269|PubMed:8102610, ECO:0000269|PubMed:9056417}.; FUNCTION: (Microbial infection) Mediates as well Human cytomegalovirus (HCMV) infection. {ECO:0000269|PubMed:8105105}.;

Recessive Scores

pRec: 0.857

Intolerance Scores

LoFtool: 0.656
RVIS EVS: -0.98
RVIS percentile EVS: 8.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.850

Gene Damage Prediction

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