NPPA natriuretic peptide A [Homo sapiens (human)] - Gene

Summary

Official Symbol: NPPAprovided by HGNC
Official Full Name: natriuretic peptide Aprovided by HGNC
Primary source: HGNC:HGNC:7939
See related: Ensembl:ENSG00000175206 MIM:108780; Vega:OTTHUMG00000002388
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ANF; ANP; CDD; CDP; PND; ATFB6; ATRST2; CDD-ANF
Summary: The protein encoded by this gene belongs to the natriuretic peptide family. Natriuretic peptides are implicated in the control of extracellular fluid volume and electrolyte homeostasis. This protein is synthesized as a large precursor (containing a signal peptide), which is processed to release a peptide from the N-terminus with similarity to vasoactive peptide, cardiodilatin, and another peptide from the C-terminus with natriuretic-diuretic activity. Mutations in this gene have been associated with atrial fibrillation familial type 6. This gene is located adjacent to another member of the natriuretic family of peptides on chromosome 1. [provided by RefSeq, Oct 2015]
Expression: Restricted expression toward heart (RPKM 12159.5) See more
Orthologs: mouse all

Genomic context

Location:: 1p36.22

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	1	NC_000001.11 (11845709..11847783, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (11905766..11907840, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

An increase in year-by-year BP variability over the past 6 years is associated with elevated plasma levels of ANP and BNP in the Japanese general population.
Title: Plasma levels of natriuretic peptides and year-by-year blood pressure variability: a population-based study.
High plasma levels of MR-proANP are associated with the incidence of atrial fibrillation and stroke in the middle-aged and elderly population.
Title: Pro-atrial natriuretic peptide and prediction of atrial fibrillation and stroke: The Malmö Preventive Project.
The young adults displayed significant negative associations between MR-proANP and several components of the metabolic syndrome, whereas such associations were not found among the adolescents besides triglycerides and diastolic BP.
Title: Associations of Proatrial Natriuretic Peptide with Components of the Metabolic Syndrome in Adolescents and Young Adults from the General Population.
In summary, there were no significant differences in ANP and BNP levels after percutaneous epicardial left atrial appendage suture ligation using LARIAT device 3 months after procedure.
Title: Atrial natriuretic peptide and brain natriuretic peptide changes after epicardial percutaneous left atrial appendage suture ligation using LARIAT device.
NPPA SNPs were not associated with insulin resistance in older adults.
Title: Brain natriuretic peptide and insulin resistance in older adults.
TIMP-4, NT-proANP, NT-proBNP were strongest associated with PAF and AHRE. The discriminatory performance of CHADS2-VASc for PAF was increased by addition of selected biomarkers.
Title: CHA2DS2-VASc score and blood biomarkers to identify patients with atrial high-rate episodes and paroxysmal atrial fibrillation.
the G allele of the genetic variant rs5068 in African Americans is associated with lower prevalence of metabolic syndrome and lower triglycerides values
Title: A favorable cardiometabolic profile is associated with the G allele of the genetic variant rs5068 in African Americans: The Multi-Ethnic Study of Atherosclerosis (MESA).
ANP inhibits TGF-beta1-induced EMT in 16HBE-14o and A549 cells through cGMP/PKG signaling, by which it targets TGF-beta1/Smad3 via attenuating phosphorylation of Smad3. These findings suggest the potential of ANP in the treatment on pulmonary diseases with airway remodeling.
Title: Atrial natriuretic peptide: A novel mediator for TGF-β1-induced epithelial-mesenchymal transition in 16HBE-14o and A549 cells.
the ANP T1766C gene polymorphism may be associated with the risk of essential hypertension, and the 1766C allele may be a protective factor against the disease
Title: Association of Polymorphisms in the Atrial Natriuretic Factor Gene with the Risk of Essential Hypertension: A Systematic Review and Meta-Analysis.
increased plasma proANP should be a protective factor of hyperuricemia among middle-aged and old women
Title: Association between plasma proANP and hyperuricemia in Chinese Han women: a cross-sectional study.

Submit: New GeneRIF Correction See all GeneRIFs (180)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Atrial fibrillation, familial, 6 MedGen: C2677294 OMIM: 612201 GeneReviews: Not available	Compare labs
Atrial standstill 2 MedGen: C3810401 OMIM: 615745 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association study identifies eight loci associated with blood pressure. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

Go to the top of the page Help

Amyloid fiber formation, organism-specific biosystem (from REACTOME)
Amyloid fiber formation, organism-specific biosystemAmyloid is a term used to describe deposits of fibrillar proteins, typically extracellular. The abnormal accumulation of amyloid, amyloidosis, is a term associated with tissue damage caused by amyloi...
Cardiac Hypertrophic Response, organism-specific biosystem (from WikiPathways)
Cardiac Hypertrophic Response, organism-specific biosystemIntegrated schematic of the more extensively characterized intracellular signal-transduction pathways that coordinate the cardiac hypertrophic response. During development and in response to physiolo...
Cardiac conduction, organism-specific biosystem (from REACTOME)
Cardiac conduction, organism-specific biosystemThe normal sequence of contraction of atria and ventricles of the heart require activation of groups of cardiac cells. The mechanism must elicit rapid changes in heart rate and respond to changes in ...
Gene Expression, organism-specific biosystem (from REACTOME)
Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
HIF-1 signaling pathway, organism-specific biosystem (from KEGG)
HIF-1 signaling pathway, organism-specific biosystemHypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a c...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystem (from WikiPathways)
MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystemThis pathway shows the role of microRNAs in the process of cardiac hypertrophy. MicroRNA targets were predicted by the TargetScan algorithm, and the predicted interactions are shown in red dashed lin...
Muscle contraction, organism-specific biosystem (from REACTOME)
Muscle contraction, organism-specific biosystemIn this module, the processes by which calcium binding triggers actin - myosin interactions and force generation in smooth and striated muscle tissues are annotated.
Physiological factors, organism-specific biosystem (from REACTOME)
Physiological factors, organism-specific biosystemCardiovascular homeostasis can be regulated by natriuretic peptides (Pandey 2014).
YAP1- and WWTR1 (TAZ)-stimulated gene expression, organism-specific biosystem (from REACTOME)
YAP1- and WWTR1 (TAZ)-stimulated gene expression, organism-specific biosystemYAP1 and WWTR1 (TAZ) are transcriptional co-activators, both homologues of the Drosophila Yorkie protein. They both interact with members of the TEAD family of transcription factors, and WWTR1 intera...

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

NPPA (e-PCR)
- UniSTS:253991

SHGC-74238 (e-PCR)
- UniSTS:43068

GDB:226664 (e-PCR)
- UniSTS:156242

RH80468 (e-PCR)
- UniSTS:87961

GDB:196313 (e-PCR)
- UniSTS:155824

GDB:549199 (e-PCR)
- UniSTS:157630

Nppa (e-PCR), detects polymorphism
- UniSTS:167638

Homology

Homologs of the NPPA gene: The NPPA gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Orthologs from Annotation Pipeline: 149 organisms have orthologs with human gene NPPA
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
hormone receptor binding	IPI Inferred from Physical Interaction more info	PubMed
neuropeptide hormone activity	IMP Inferred from Mutant Phenotype more info	PubMed
neuropeptide receptor binding	IMP Inferred from Mutant Phenotype more info	PubMed
peptide hormone receptor binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
signaling receptor binding	IDA Inferred from Direct Assay more info	PubMed
signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
cGMP biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
cardiac muscle hypertrophy in response to stress	IEA Inferred from Electronic Annotation more info
cell growth involved in cardiac muscle cell development	IEA Inferred from Electronic Annotation more info
cellular protein metabolic process	TAS Traceable Author Statement more info
cellular response to mechanical stimulus	IEA Inferred from Electronic Annotation more info
female pregnancy	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of cell growth	IEA Inferred from Electronic Annotation more info
negative regulation of collecting lymphatic vessel constriction	IEA Inferred from Electronic Annotation more info
negative regulation of systemic arterial blood pressure	IEA Inferred from Electronic Annotation more info
neuropeptide signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of delayed rectifier potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of heart rate	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of histamine secretion by mast cell	IEA Inferred from Electronic Annotation more info
positive regulation of potassium ion export across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
protein folding	IDA Inferred from Direct Assay more info	PubMed
receptor guanylyl cyclase signaling pathway	IDA Inferred from Direct Assay more info	PubMed
regulation of atrial cardiac muscle cell membrane repolarization	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of blood pressure	IDA Inferred from Direct Assay more info	PubMed
regulation of blood vessel size	IEA Inferred from Electronic Annotation more info
regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	ISS Inferred from Sequence or Structural Similarity more info	PubMed
regulation of cardiac conduction	TAS Traceable Author Statement more info
regulation of high voltage-gated calcium channel activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
regulation of signaling receptor activity	IEA Inferred from Electronic Annotation more info
response to hypoxia	IEA Inferred from Electronic Annotation more info
response to insulin	IEA Inferred from Electronic Annotation more info
response to muscle stretch	TAS Traceable Author Statement more info	PubMed
transcription initiation from RNA polymerase II promoter	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
collagen-containing extracellular matrix	HDA more info	PubMed
extracellular region	NAS Non-traceable Author Statement more info	PubMed
extracellular region	TAS Traceable Author Statement more info
extracellular space	IEA Inferred from Electronic Annotation more info
mast cell granule	IEA Inferred from Electronic Annotation more info
nucleus	IEA Inferred from Electronic Annotation more info
perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: natriuretic peptides A

Names: atriopeptin; cardiodilatin-related peptide; cardionatrin; natriuretic peptide precursor A variant 1; prepronatriodilatin

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.