XPNPEP3

X-prolyl aminopeptidase 3, the group of M24 metallopeptidase family|Aminopeptidases

Basic information

Region (hg38): 22:40857077-40932815

Links

ENSG00000196236 ∙ NCBI:63929 ∙ OMIM:613553 ∙ HGNC:28052 ∙ Uniprot:Q9NQH7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephronophthisis-like nephropathy 1 (Limited), mode of inheritance: AR
• nephronophthisis-like nephropathy 1 (Strong), mode of inheritance: AR
• late-onset nephronophthisis (Supportive), mode of inheritance: AR
• nephronophthisis-like nephropathy 1 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephronophthisis-like nephropathy 1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Neurologic; Renal	20179356
Avoidance of nephrotoxic medications may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XPNPEP3 gene.

• Nephronophthisis-like nephropathy 1 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XPNPEP3 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			2	23		25
missense			59		1	60
nonsense	2	1				3
start loss						0
frameshift		2				2
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			4	7		11
non coding			132	27	37	196
Total	2	5	193	50	38

Variants in XPNPEP3

This is a list of pathogenic ClinVar variants found in the XPNPEP3 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-40857095-C-T		Nephronophthisis-Like Nephropathy	Uncertain significance (Jun 14, 2016)
22-40857138-C-T		Nephronophthisis-Like Nephropathy	Uncertain significance (Jun 14, 2016)
22-40857141-C-A		Nephronophthisis-Like Nephropathy	Uncertain significance (Jun 14, 2016)
22-40857154-C-G		Nephronophthisis-like nephropathy 1	Uncertain significance (Jan 13, 2018)
22-40857159-C-T		Nephronophthisis-like nephropathy 1	Benign (Jan 13, 2018)
22-40857221-G-A		Inborn genetic diseases	Uncertain significance (Nov 22, 2022)
22-40857228-A-T		Nephronophthisis-like nephropathy 1	Uncertain significance (Aug 16, 2022)
22-40857232-C-T		Nephronophthisis-like nephropathy 1	Likely benign (Oct 13, 2022)
22-40857243-C-A			Uncertain significance (Sep 16, 2018)
22-40857244-A-G		Nephronophthisis-like nephropathy 1	Likely benign (Jul 19, 2023)
22-40857250-G-C		Nephronophthisis-like nephropathy 1	Uncertain significance (Jun 10, 2022)
22-40857254-C-A		Nephronophthisis-like nephropathy 1	Likely benign (Jun 15, 2023)
22-40861069-C-G		not specified	Uncertain significance (Jan 03, 2024)
22-40861075-C-T		not specified	Uncertain significance (Oct 03, 2022)
22-40861105-C-T		not specified	Likely benign (Dec 17, 2023)
22-40861118-T-C		not specified	Uncertain significance (Jun 22, 2023)
22-40861126-C-T		not specified	Uncertain significance (Sep 21, 2023)
22-40861154-T-C		not specified	Uncertain significance (Oct 06, 2022)
22-40861189-C-T		not specified	Uncertain significance (Oct 20, 2023)
22-40861307-C-T		not specified	Uncertain significance (Mar 01, 2024)
22-40861334-A-C		not specified	Uncertain significance (Mar 01, 2024)
22-40861352-C-A		not specified	Uncertain significance (May 21, 2024)
22-40861395-A-T		not specified	Uncertain significance (Jan 06, 2023)
22-40861439-A-G		not specified	Uncertain significance (Mar 04, 2024)
22-40861453-A-G		not specified	Uncertain significance (Oct 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XPNPEP3	protein_coding	protein_coding	ENST00000357137	10	110758

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.86e-8	0.965	125668	0	80	125748	0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0995	290	285	1.02	0.0000161	3316
Missense in Polyphen		81	92.522	0.87547		1025
Synonymous	0.237	99	102	0.970	0.00000539	1002
Loss of Function	2.07	17	29.0	0.586	0.00000193	289

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000753	0.000752
Ashkenazi Jewish	0.00	0.00
East Asian	0.000652	0.000653
Finnish	0.000371	0.000370
European (Non-Finnish)	0.000352	0.000352
Middle Eastern	0.000652	0.000653
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Leu-Pro-Ala (PubMed:25609706, PubMed:28476889). Also shows low activity towards peptides with Ala or Ser at the P1 position (PubMed:28476889). {ECO:0000269|PubMed:25609706, ECO:0000269|PubMed:28476889}.

Recessive Scores

• pRec: 0.138

Intolerance Scores

• loftool: 0.647
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.6

Haploinsufficiency Scores

• pHI: 0.138
• hipred: N
• hipred_score: 0.198
• ghis: 0.579

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.826

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xpnpep3

Zebrafish Information Network

• Gene name: xpnpep3
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: glomerular filtration;proteolysis;protein processing
• Cellular component: cytoplasm;mitochondrion
• Molecular function: aminopeptidase activity;protein binding;manganese ion binding;protein homodimerization activity;metalloaminopeptidase activity