XPNPEP1

protein-coding

X-prolyl aminopeptidase 1, the group of Aminopeptidases|M24 metallopeptidase family

Gene summary

This gene encodes the cytosolic form of a metalloaminopeptidase that catalyzes the cleavage of the N-terminal amino acid adjacent to a proline residue. The gene product may play a role in degradation and maturation of tachykinins, neuropeptides, and peptide hormones. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Nov 2009]

Previous symbols:

XPNPEP
XPNPEPL1
XPNPEPL

MANE transcript

NM_020383.4

Inheritance

—

ClinVar variants

U:89B:5

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr10:109,864,766-109,923,553

External References & Databases

Ensembl (ENSG00000108039)

Transcript & Mutation Effects

hg38 • Region Span ~58.8 kb

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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 XPNPEP1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 79

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020383.4. 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			2 clinvar	1 clinvar		3
missense			80 clinvar	4 clinvar		84
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	89	5	0	94

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 78 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020383.4	RefSeq	NP_065116.3	21	MANE Select
ENST00000502935.6	Ensembl	ENSP00000421566.1	21	MANE Select
NM_001167604.2	RefSeq	NP_001161076.1	20	Standard
NM_001324128.2	RefSeq	NP_001311057.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
bradykinin catabolic process

Molecular Function

aminopeptidase activity
manganese ion binding
protein homodimerization activity
metalloaminopeptidase activity

Cellular Component

cytoplasm
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000502935
Coding exons: 21
Length: 58788
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.42	253	387	0.653	0.0000219	4369
Missense (PolyPhen)		53	127.17	0.41677		1376
Synonymous	-1.18	158	140	1.13	0.00000829	1273
Loss of Function	4.49	9	39.4	0.229	0.00000195	466

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Contributes to the degradation of bradykinin. Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Arg-Pro-Pro.;

Recessive Scores

pRec: 0.278

Intolerance Scores

LoFtool: 0.0818
RVIS EVS: -0.73
RVIS percentile EVS: 14.02

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.881

Gene Damage Prediction

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