NAPSA

protein-coding

napsin A aspartic peptidase, the group of Peptidase family A1

Gene summary

This gene encodes a member of the peptidase A1 family of aspartic proteases. The encoded preproprotein is proteolytically processed to generate an activation peptide and the mature protease. The activation peptides of aspartic proteinases function as inhibitors of the protease active site. These peptide segments, or pro-parts, are deemed important for correct folding, targeting, and control of the activation of aspartic proteinase zymogens. The encoded protease may play a role in the proteolytic processing of pulmonary surfactant protein B in the lung and may function in protein catabolism in the renal proximal tubules. This gene has been described as a marker for lung adenocarcinoma and renal cell carcinoma. [provided by RefSeq, Feb 2016]

MANE transcript

NM_004851.3

Inheritance

—

ClinVar variants

U:80B:6

Top phenotype

Myoepithelial tumor

gnomAD constraint

pLI —, LoF o/e 1.12

Max pathogenic AF

—

Genomic locus

chr19:50,358,472-50,365,830

External References & Databases

Ensembl (ENSG00000131400)

Transcript & Mutation Effects

hg38 • Region Span ~7.4 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 NAPSA variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 77

not providedTotal: 2

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004851.3. 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			2 clinvar	1 clinvar	1 clinvar	4
missense			76 clinvar	3 clinvar	1 clinvar	80
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	80	4	2	86

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004851.3	RefSeq	NP_004842.1	9	MANE Select
ENST00000253719.7	Ensembl	ENSP00000253719.1	9	MANE Select
NM_001436336.1	RefSeq	NP_001423265.1	9	Standard
NM_001436337.1	RefSeq	NP_001423266.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysosome - Homo sapiens (human)
Surfactant metabolism
Metabolism of proteins

Biological Process

proteolysis
protein catabolic process
membrane protein proteolysis
surfactant homeostasis
cellular protein metabolic process

Molecular Function

endopeptidase activity
aspartic-type endopeptidase activity
peptidase activity

Cellular Component

extracellular space
lysosome
extracellular exosome
alveolar lamellar body
multivesicular body lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000253719
Coding exons: 9
Length: 7354
Individuals with no LoFs: 125628
Homozygous LoFs: 0
Heterozygous LoFs: 120
Defined: 125748
p: 0.000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.158	252	259	0.972	0.0000154	2662
Missense (PolyPhen)		96	112.56	0.85291		1180
Synonymous	0.363	112	117	0.957	0.00000752	941
Loss of Function	-0.456	19	17.0	1.12	8.70e-7	186

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0052	0.0052	notable
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000095	0.000092	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00020	0.00020	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in processing of pneumocyte surfactant precursors.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.816
RVIS EVS: -0.04
RVIS percentile EVS: 50.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.121

Gene Damage Prediction

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