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FLASH GENE

Symbol

NPPB

contributors: mct - updated : 06-05-2015

HGNC name	natriuretic peptide precursor B
HGNC id	7940

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	1p36.22      Physical location : 11.917.521 - 11.918.992
Synonym name	gamma-brain natriuretic peptide
	brain type natriuretic peptide
	natriuretic protein
Synonym symbol(s)	BNP, ANFB

DNA

TYPE	functioning gene
STRUCTURE	1.47 kb     3 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	full-length promoter is more active in ventricular versus atrial myocytes and essentially inactive in fibroblasts, the distal promoter contains both positive and negative regulatory elements, a region of the proximal promoter located between -127 and -40 confers tissue specificity

MAPPING

cloned

Y

linked

status

confirmed

Map	pter - D1S1414 - 1437 - NPPB - D1S1305 - D1S1753E - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002521 3 - 708 NP_002512 - 134 - 2008 18823968

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac

cell lineage

cell lines

fluid/secretion

at STAGE

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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