NPPB
protein-codingnatriuretic peptide B, the group of Neuropeptides
Gene summary
This gene is a member of the natriuretic peptide family and encodes a secreted protein which functions as a cardiac hormone. The protein undergoes two cleavage events, one within the cell and a second after secretion into the blood. The protein's biological actions include natriuresis, diuresis, vasorelaxation, inhibition of renin and aldosterone secretion, and a key role in cardiovascular homeostasis. A high concentration of this protein in the bloodstream is indicative of heart failure. The presence of myocardial injury is a significant predictor of mortality in hospitalized coronavirus disease 2019 (COVID-19) patients, and there is evidence of increased levels of natriuretic peptide B in hospitalized non-survivor COVID-19 patients. The protein also acts as an antimicrobial peptide with antibacterial and antifungal activity. Mutations in this gene have been associated with postmenopausal osteoporosis. [provided by RefSeq, Aug 2020]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.5 kbGenCC 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 NPPB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002521.3. 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 | 2 | ||||
| missense | 22 | 1 | 3 | 26 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 22 | 1 | 5 | 28 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002512.1 | 3 | MANE Select | |
| Ensembl | ENSP00000365651.3 | 3 | MANE Select | |
| Ensembl | ENSP00000615913.1 | 3 | Standard | |
| Ensembl | ENSP00000615913.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- cGMP-PKG signaling pathway - Homo sapiens (human)
- MicroRNAs in cardiomyocyte hypertrophy
- NO-cGMP-PKG mediated Neuroprotection
- alk in cardiac myocytes
Biological Process
- negative regulation of systemic arterial blood pressure
- cGMP biosynthetic process
- protein folding
- cell surface receptor signaling pathway
- receptor guanylyl cyclase signaling pathway
Molecular Function
- signaling receptor binding
- hormone activity
- protein binding
- diuretic hormone activity
- hormone receptor binding
Cellular Component
- extracellular region
- extracellular space
- nucleus
- cytoplasm
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376468
- Coding exons
- 3
- Length
- 1468
- Individuals with no LoFs
- 125712
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125744
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.152 | 88 | 84.1 | 1.05 | 0.00000523 | 840 |
| Missense (PolyPhen) | 20 | 19.255 | 1.0387 | 218 | ||
| Synonymous | 0.101 | 34 | 34.8 | 0.978 | 0.00000184 | 302 |
| Loss of Function | -0.414 | 7 | 5.91 | 1.18 | 3.50e-7 | 59 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0.00096 | 0.00089 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cardiac hormone which may function as a paracrine antifibrotic factor in the heart. Also plays a key role in cardiovascular homeostasis through natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion. Specifically binds and stimulates the cGMP production of the NPR1 receptor. Binds the clearance receptor NPR3. {ECO:0000269|PubMed:1672777}.;
Intolerance Scores
- LoFtool
- 0.700
- RVIS EVS
- 0.53
- RVIS percentile EVS
- 80.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.557
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |