NPEPPS

protein-coding

aminopeptidase puromycin sensitive, the group of Aminopeptidases|M1 metallopeptidases

Gene summary

This gene encodes the puromycin-sensitive aminopeptidase, a zinc metallopeptidase which hydrolyzes amino acids from the N-terminus of its substrate. The protein has been localized to both the cytoplasm and to cellular membranes. This enzyme degrades enkaphalins in the brain, and studies in mouse suggest that it is involved in proteolytic events regulating the cell cycle. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006310.4

Inheritance

—

ClinVar variants

U:82B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr17:47,522,942-47,624,665

External References & Databases

Ensembl (ENSG00000141279)

Transcript & Mutation Effects

hg38 • Region Span ~101.7 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 NPEPPS variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006310.4. 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				1 clinvar	3 clinvar	4
missense			70 clinvar	2 clinvar		72
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	82	3	3	88

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006310.4	RefSeq	NP_006301.3	23	MANE Select
ENST00000322157.9	Ensembl	ENSP00000320324.4	23	MANE Select
NM_001330257.2	RefSeq	NP_001317186.1	24	Standard
NM_001411130.1	RefSeq	NP_001398059.1	24	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein polyubiquitination
proteolysis
peptide catabolic process
cellular response to hypoxia
positive regulation of protein targeting to mitochondrion

Molecular Function

aminopeptidase activity
zinc ion binding
peptide binding
metalloaminopeptidase activity

Cellular Component

nucleus
cytoplasm
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000322157
Coding exons: 23
Length: 100335
Individuals with no LoFs: 121529
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 121532
p: 0.0000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.98	222	463	0.479	0.0000236	5944
Missense (PolyPhen)		35	161.24	0.21706		2125
Synonymous	0.893	148	162	0.911	0.00000815	1733
Loss of Function	6.42	0	48.0	0.00	0.00000245	623

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000030	0.000030	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Aminopeptidase with broad substrate specificity for several peptides. Involved in proteolytic events essential for cell growth and viability. May act as regulator of neuropeptide activity. Plays a role in the antigen-processing pathway for MHC class I molecules. Involved in the N-terminal trimming of cytotoxic T-cell epitope precursors. Digests the poly-Q peptides found in many cellular proteins. Digests tau from normal brain more efficiently than tau from Alzheimer disease brain. {ECO:0000269|PubMed:10978616, ECO:0000269|PubMed:11062501, ECO:0000269|PubMed:17154549, ECO:0000269|PubMed:17318184, ECO:0000269|PubMed:19917696}.;

Recessive Scores

pRec: 0.200

Intolerance Scores

LoFtool: 0.374
RVIS EVS: 0.04
RVIS percentile EVS: 57.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.795

Gene Damage Prediction

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