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FLASH GENE
Symbol NPPB contributors: mct - updated : 06-05-2015
HGNC name natriuretic peptide precursor B
HGNC id 7940
PROTEIN
PHYSICAL PROPERTIES globular
STRUCTURE
motifs/domains
  • conserved 17-AAs disulfide-linked ring structure that is required for biological activity
    • HOMOLOGY
    interspecies homolog to murine nppb
    Homologene
    FAMILY
  • natriuretic peptide family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • directly influencing blood pressure, body fluid homeostasis and cardiovascular improving heart function
  • functioning as a cardiac hormone
  • may also play a role in energy metabolism and metabolic diseases
  • cardiac hormone with systemic haemodynamic effects as well as local cytoprotective and antiproliferative properties
  • NPPB, NPPA, NPPC activate guanylyl cyclase suggesting a potential role in maintaining lens epithelial cell homeostasis (PMID;
  • controls early load-dependent regulation of ATP2A1 through calcineurin
  • possesses cardiorenal protective actions
  • may play an important role in regulating blood pressure and remodeling of the heart
  • involved in the endochondral ossification signalling
  • importance of the endogenous NPPA/NPPB-NPR1 system not only in the neovascularization of ischemic tissues but also in embryonic vascular development and organ morphogenesis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • direct target of SHOX (similar to SHOX, may play a role in chondrocyte maturation and, as a downstream target of SHOX might act as a mediator of the SHOX actions)
  • specific HIF1alpha target gene
  • SHOX2, like SHOX, regulates NPPB directly
  • GSN induces cardiomyocyte hypertrophy and NPPB expression via MAPK14 signaling and GATA4 transcriptional factor activation
    • cell & other
    REGULATION
    activated by directly activated by SHOX
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    increasing progressively with worsening symptoms in severe mitral regurgitation
    constitutional     --over  
    transiently increased in patients with intracerebal large-artery atherosclerosis independently of heart disease, and reflected infarct volume and the severity of acute ischemic stroke
    constitutional     --over  
    plasma concentrations correlate with the extent of atrial fibrillation-associated silent brain lesions
    constitutional     --over  
    significant predictors of death and/or complicated clinical course in acute pulmonary embolism
    constitutional     --over  
    significantly with severity of mitral regurgitation secondary to ischemic and nonischemic dilated cardiomyopathy
    constitutional     --over  
    of TNNT2 and NPPB are associated with increased risk of cardioembolic and other nonlacunar ischemic strokes
    Susceptibility
  • to postmenopausal osteoporosis
  • type 2 diabetes
  • to blood pressure variation
    • Variant & Polymorphism other
  • variant increasing the risk of postmenopausal osteoporosis
  • T-381C polymorphism was associated with lower plasma glucose levels and lower type 2 diabetes risk, and with higher bone-mineral density in Japanese postmenopausal women
  • Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension
    • Candidate gene
    Marker
  • marker of preeclampsia (concentration of NPPB was higher in pre-eclamptic women, and is associated with the (TTTC) genotypes)
  • NPPB and TNNI3 are useful markers for identifying patients at risk for clinical deteriorations, and combined measurements of these biomarkers further improves the prognostic value of increased cardiovascular events in hypertrophic cardiomyopathy (HCM)
  • plasma NPPB was found to be an independent predictor of endothelial function
  • vis a useful diagnostic marker of acute Kawasaki disease in children
  • used as a therapeutic and a biomarker for heart failure (HF)
  • predictive of all-cause mortality, suggesting that this biomarker may potentially be used to refine clinical risk stratification in anticoagulated patients with atrial fibrillation
    • Therapy target
  • BNP level is significant and equivalent indicator of coronary artery disease and left ventricular hypertrophy in asymptomatic patients with chronic kidney disease
  • induction of NPPB may contribute to the potential benefits of pharmacological HIF inducers in the treatment of ischaemic heart disease and heart failure
    • ANIMAL & CELL MODELS