XPNPEP2

X-prolyl aminopeptidase 2, the group of M24 metallopeptidase family|Aminopeptidases

Basic information

Region (hg38): X:129738949-129769536

Links

ENSG00000122121 ∙ NCBI:7512 ∙ OMIM:300145 ∙ HGNC:12823 ∙ Uniprot:O43895 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Angioedema induced by ACE inhibitors, susceptibility to	XL	Pharmacogenomic	Medication selection would be impacted in individuals with relevant variants	General	16175507

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XPNPEP2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XPNPEP2 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				6	1	7
missense			32	2		34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1	3	4
Total	0	0	32	9	4

Variants in XPNPEP2

This is a list of pathogenic ClinVar variants found in the XPNPEP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-129739220-C-T		not specified	Likely benign (Oct 02, 2023)
X-129741825-C-T			Benign (Nov 13, 2018)
X-129742002-G-A			Benign (Nov 13, 2018)
X-129742179-C-G		not specified	Uncertain significance (Nov 17, 2022)
X-129745227-G-C			Uncertain significance (Dec 01, 2023)
X-129745242-A-G			Uncertain significance (-)
X-129746286-T-C			Uncertain significance (-)
X-129746311-T-A		not specified	Uncertain significance (Aug 15, 2023)
X-129746336-G-A			Uncertain significance (-)
X-129746587-T-C			Likely benign (Jul 01, 2023)
X-129746609-A-G		not specified	Uncertain significance (Jan 03, 2024)
X-129746638-T-C		not specified	Benign (Mar 15, 2016)
X-129746664-C-T		not specified	Uncertain significance (May 09, 2022)
X-129747631-C-A		not specified	Uncertain significance (Nov 06, 2023)
X-129747659-G-T			Likely benign (Mar 01, 2022)
X-129747709-C-T		not specified	Uncertain significance (Jan 24, 2024)
X-129750489-T-C		not specified	Uncertain significance (Dec 09, 2023)
X-129750539-G-A		not specified	Uncertain significance (Dec 28, 2022)
X-129750542-C-A		not specified	Uncertain significance (Jul 06, 2021)
X-129751753-A-C		Susceptibility to angioedema induced by ACE inhibitors	Uncertain significance (Apr 04, 2024)
X-129752170-G-A		not specified	Uncertain significance (Mar 04, 2024)
X-129752186-C-T			Likely benign (Mar 01, 2023)
X-129752253-C-T		not specified	Uncertain significance (Jan 31, 2024)
X-129752323-G-A		not specified	Uncertain significance (Jan 18, 2023)
X-129752356-C-T		not specified	Likely benign (Feb 04, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XPNPEP2	protein_coding	protein_coding	ENST00000371106	21	30565

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.87e-13	0.252	125666	36	45	125747	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.338	288	272	1.06	0.0000216	4371
Missense in Polyphen		94	92.749	1.0135		1432
Synonymous	-0.779	117	107	1.10	0.00000874	1325
Loss of Function	1.10	23	29.4	0.782	0.00000214	465

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000484	0.000440
Ashkenazi Jewish	0.00	0.00
East Asian	0.00144	0.00109
Finnish	0.00	0.00
European (Non-Finnish)	0.000430	0.000308
Middle Eastern	0.00144	0.00109
South Asian	0.000737	0.000457
Other	0.000442	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Membrane-bound metalloprotease which catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Arg-Pro-Pro. May play a role in the metabolism of the vasodilator bradykinin. {ECO:0000269|PubMed:15361070}.
• Disease: DISEASE: Angioedema induced by ACE inhibitors (AEACEI) [MIM:300909]: A potentially life-threatening side effect of ACE inhibitors that appears in a subset of patients taking these drugs for hypertension and cardiovascular disease treatment. AEACEI is characterized by swelling of the face, lips, tongue, and airway that can lead to suffocation and death if severe. {ECO:0000269|PubMed:16175507, ECO:0000269|PubMed:20625347, ECO:0000269|PubMed:21898657}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins (Consensus)

Recessive Scores

• pRec: 0.138

Intolerance Scores

• loftool: 0.783
• rvis_EVS: -0.38
• rvis_percentile_EVS: 28.11

Haploinsufficiency Scores

• pHI: 0.446
• hipred: N
• hipred_score: 0.281
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.130

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xpnpep2

Gene ontology

• Biological process: proteolysis
• Cellular component: extracellular region;cytoplasm;plasma membrane;membrane;anchored component of membrane;extracellular exosome
• Molecular function: aminopeptidase activity;metal ion binding;metalloaminopeptidase activity