NPPB (Natriuretic peptides B) variants and mutations
NPPB (also known as Natriuretic peptides B) is a human protein-coding gene encoding a natriuretic peptides B protein. It is processed to B-type natriuretic peptide, which is released in response to ventricular wall stress and promotes natriuresis and vasodilation. BNP and its inactive cleavage fragment NT-proBNP are widely used biomarkers for diagnosis and monitoring of heart failure. This analysis covers 351 NPPB variants and mutations. Of these, 86% have computational variant effect predictions. Disease context includes hypertensive disorder, Increased blood pressure, and neurodegenerative disease. Example NPPB variants include M1?, D2E, and D2H.
Variant analysis overview
- Gene: NPPB
- Protein: Natriuretic peptides B
- UniProt accession: P16860
- Organism: Homo sapiens
- Variants analyzed: 351
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 182 unspecified-consequence records; 85 missense variants; 65 synonymous variants; 16 frameshift variants; 2 splice-region variants; 1 in-frame deletions; 2 stop-gained variants; 1 substitution
- Prediction scores: 302 variants have prediction scores (86% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypertensive disorder, Increased blood pressure, neurodegenerative disease, major depressive disorder, alcohol drinking, viral eye infection, spinal cord injury, ankylosing spondylitis, atrial fibrillation, hydrops fetalis, heart failure, chronic kidney disease.
Protein structure and variant hotspots
- Protein features: 8 post-translational modification sites.
- PTM context: 27 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable NPPB variants
Examples include M1?, D2E, D2H, D2N, P3L, P3S, P3A, Q4*. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV6468, Variant assessed as somatic; high impact.
- D2E (p.Asp2Glu), TOPMed rs1347544955, gnomAD rs1347544955, REVEL 0.03, CADD 11.70
- D2H (p.Asp2His), ExAC rs753423994, TOPMed rs753423994, gnomAD rs753423994, REVEL 0.06, CADD 19.10
- D2N (p.Asp2Asn), ExAC rs753423994, TOPMed rs753423994, gnomAD rs753423994, REVEL 0.08, CADD 14.60
- P3L (p.Pro3Leu), Ensembl rs1459920048
- P3S (p.Pro3Ser), gnomAD 1-11858827-G-GA, CADD 16.90
- P3A (p.Pro3Ala), gnomAD 1-11858827-G-C, REVEL 0.09, CADD 4.40
- Q4* (p.Gln4Ter), gnomAD rs1163479003, CADD 33.00
- Q4H (p.Gln4His), NCI-TCGA Cosmic COSV6468, Variant assessed as somatic; moderate impact.
- Q4R (p.Gln4Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- T5A (p.Thr5Ala), ExAC rs779385648, TOPMed rs779385648, gnomAD rs779385648, REVEL 0.02, CADD 14.80, Uncertain significance, not specified
- T5I (p.Thr5Ile), Ensembl rs1570558857, REVEL 0.04, CADD 15.00
- T5K (p.Thr5Lys), Ensembl rs1570558857
- T5T (p.Thr5Thr), rs1645136384, gnomAD 1-11858819-T-C, CADD 0.48
- A6T (p.Ala6Thr), gnomAD 1-11858818-C-T, REVEL 0.02, CADD 8.56
- P7T (p.Pro7Thr), TOPMed rs1054778790, gnomAD rs1054778790, REVEL 0.03, CADD 5.28, Uncertain significance, not specified
- P7P (p.Pro7Pro), gnomAD 1-11858813-A-G, CADD 4.89
- P7S (p.Pro7Ser), gnomAD 1-11858815-G-A, REVEL 0.04, CADD 5.45
- R9W (p.Arg9Trp), rs148807468, ClinGen CA597305, ClinVar RCV004277165, ESP rs148807468, REVEL 0.03, CADD 13.50, Uncertain significance, not specified
- R9G (p.Arg9Gly), gnomAD 1-11858808-CG-C, CADD 13.80
- R9P (p.Arg9Pro), gnomAD 1-11858808-C-G, REVEL 0.10, CADD 21.50
- A10E (p.Ala10Glu), 1000Genomes rs144265843, ExAC rs144265843, TOPMed rs144265843, gnomAD rs144265843, REVEL 0.09, CADD 4.63
- A10T (p.Ala10Thr), ExAC rs543699023, TOPMed rs543699023, gnomAD rs543699023, REVEL 0.04, CADD 4.12
- A10A (p.Ala10Ala), rs763718693, gnomAD 1-11858804-C-T, CADD 0.25
- L11F (p.Leu11Phe), NCI-TCGA TCGA novel, TOPMed rs1645136249, gnomAD rs1645136249, REVEL 0.03, CADD 5.48, Variant assessed as somatic; moderate impact.
- L11H (p.Leu11His), gnomAD 1-11858802-A-T, REVEL 0.11, CADD 23.00
- L12P (p.Leu12Pro), gnomAD rs1487798383, REVEL 0.12, CADD 18.60
- L12Q (p.Leu12Gln), gnomAD rs1487798383
- L12L (p.Leu12Leu), rs1264886426, gnomAD 1-11858798-C-T, CADD 6.96
- L13F (p.Leu13Phe), ExAC rs751286475, TOPMed rs751286475, gnomAD rs751286475, REVEL 0.02, CADD 13.40
- L14R (p.Leu14Arg), gnomAD 1-11858793-A-C, REVEL 0.31, CADD 23.70
- L14F (p.Leu14Phe), rs757672495, gnomAD 1-11858794-G-GGGG, CADD 21.90
- L15L (p.Leu15Leu), rs763044821, gnomAD 1-11858789-G-C, CADD 0.90
- L17F (p.Leu17Phe), gnomAD 1-11858783-C-G, REVEL 0.11, CADD 14.20
- H18H (p.His18His), rs35628673, gnomAD 1-11858780-A-G, CADD 4.64
- H18Y (p.His18Tyr), gnomAD 1-11858782-G-A, REVEL 0.03, CADD 1.46
- L19L (p.Leu19Leu), rs1191407761, gnomAD 1-11858777-C-G, CADD 5.55
- F21F (p.Phe21Phe), rs765349605, gnomAD 1-11858771-G-A, CADD 1.65
- F21V (p.Phe21Val), gnomAD 1-11858773-A-C, REVEL 0.02, CADD 5.08
- F21L (p.Phe21Leu), gnomAD 1-11858773-A-G, REVEL 0.05, CADD 3.72
- L22W (p.Leu22Trp), gnomAD 1-11858769-AG-A, CADD 21.70
- G23A (p.Gly23Ala), ExAC rs777336949, gnomAD rs777336949, REVEL 0.05, CADD 16.70
- G23R (p.Gly23Arg), ExAC rs760123248, gnomAD rs760123248, REVEL 0.05, CADD 14.50
- G24A (p.Gly24Ala), Ensembl rs2100684067
- G24G (p.Gly24Gly), gnomAD 1-11858762-A-G, CADD 1.89
- G24V (p.Gly24Val), gnomAD 1-11858763-C-A, REVEL 0.01, CADD 13.40
- R25L (p.Arg25Leu), rs5227, ClinGen CA597292, ClinVar RCV000882537, UniProt VAR 014580, REVEL 0.01, CADD 0.05, Benign, not provided
- R25R (p.Arg25Arg), rs150360910, gnomAD 1-11858759-A-G, CADD 2.19
- R25H (p.Arg25His), gnomAD 1-11858760-C-T, REVEL 0.00, CADD 0.02
- R25C (p.Arg25Cys), gnomAD 1-11858761-G-A, REVEL 0.09, CADD 22.90
- R25G (p.Arg25Gly), gnomAD 1-11858761-G-C, REVEL 0.07, CADD 21.80
- S26C (p.Ser26Cys), TOPMed rs61761993, gnomAD rs61761993, REVEL 0.08, CADD 21.90
- S26F (p.Ser26Phe), TOPMed rs61761993, gnomAD rs61761993, REVEL 0.09, CADD 22.30
- S26S (p.Ser26Ser), gnomAD 1-11858756-G-A, CADD 1.30
- S26P (p.Ser26Pro), gnomAD 1-11858758-A-G, REVEL 0.01, CADD 10.90
- H27Q (p.His27Gln), 1000Genomes rs564298750, REVEL 0.06, CADD 22.20
- H27H (p.His27His), rs564298750, gnomAD 1-11858753-G-A, CADD 4.57
- H27T (p.His27Thr), gnomAD 1-11858754-TG-T, CADD 19.80
- P28R (p.Pro28Arg), TOPMed rs1259887805
- P28T (p.Pro28Thr), gnomAD rs1645135928, REVEL 0.26, CADD 23.30
- P28L (p.Pro28Leu), gnomAD 1-11858751-G-A, REVEL 0.29, CADD 24.40
- L29P (p.Leu29Pro), ExAC rs768381227, TOPMed rs768381227, gnomAD rs768381227, REVEL 0.19, CADD 22.90
- L29Q (p.Leu29Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L29L (p.Leu29Leu), gnomAD 1-11858749-G-A, CADD 2.35
- G30G (p.Gly30Gly), rs1456381639, gnomAD 1-11858744-G-T, CADD 1.52
- G30A (p.Gly30Ala), gnomAD 1-11858744-GC-G, CADD 18.60
- S31I (p.Ser31Ile), NCI-TCGA Cosmic COSV1009, Variant assessed as somatic; moderate impact.
- S31S (p.Ser31Ser), gnomAD 1-11858741-G-A, CADD 4.18
- S31N (p.Ser31Asn), gnomAD 1-11858742-C-T, REVEL 0.02, CADD 7.74
- P32L (p.Pro32Leu), ExAC rs748837558, gnomAD rs748837558, REVEL 0.04, CADD 16.10
- P32P (p.Pro32Pro), rs779624438, gnomAD 1-11858738-G-A, CADD 0.34
- G33R (p.Gly33Arg), 1000Genomes rs151222918, ESP rs151222918, ExAC rs151222918, TOPMed rs151222918, REVEL 0.02, CADD 1.16
- G33A (p.Gly33Ala), gnomAD 1-11858736-C-G, REVEL 0.03, CADD 0.08
- G33S (p.Gly33Ser), gnomAD 1-11858737-C-T, REVEL 0.00, CADD 0.10
- A35A (p.Ala35Ala), gnomAD 1-11858729-G-T, CADD 3.67
- S36* (p.Ser36Ter), NCI-TCGA TCGA novel, TOPMed rs1267231541, gnomAD rs1267231541, Variant assessed as somatic; high impact.
- S36L (p.Ser36Leu), TOPMed rs1267231541, gnomAD rs1267231541, REVEL 0.03, CADD 4.95
- S36S (p.Ser36Ser), rs1039076006, gnomAD 1-11858726-C-G, CADD 1.46
- D37N (p.Asp37Asn), TOPMed rs921552050, gnomAD rs921552050, REVEL 0.04, CADD 10.10
- L38L (p.Leu38Leu), rs199794109, gnomAD 1-11858720-C-T, CADD 2.37
- E39G (p.Glu39Gly), Ensembl rs1645135773
- E39K (p.Glu39Lys), NCI-TCGA Cosmic COSV6468, Variant assessed as somatic; moderate impact.
- E39E (p.Glu39Glu), rs781153609, gnomAD 1-11858717-T-C, CADD 0.52
- E39A (p.Glu39Ala), gnomAD 1-11858718-T-G, REVEL 0.04, CADD 14.80
- T40A (p.Thr40Ala), NCI-TCGA Cosmic COSV6468, Variant assessed as somatic; moderate impact.
- T40T (p.Thr40Thr), rs140816420, gnomAD 1-11858714-C-T, CADD 2.61
- T40M (p.Thr40Met), gnomAD 1-11858715-G-A, REVEL 0.05, CADD 7.79
- S41C (p.Ser41Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S41S (p.Ser41Ser), rs763747066, gnomAD 1-11858711-G-A, CADD 0.94
- G42A (p.Gly42Ala), ExAC rs765544521, gnomAD rs765544521, REVEL 0.05, CADD 0.65
- G42E (p.Gly42Glu), ExAC rs765544521, gnomAD rs765544521, REVEL 0.04, CADD 2.46
- G42R (p.Gly42Arg), ExAC rs758657926, gnomAD rs758657926, REVEL 0.01, CADD 2.31
- L43L (p.Leu43Leu), gnomAD 1-11858705-T-C, CADD 5.87
- Q44H (p.Gln44His), rs751994081, gnomAD 1-11858702-C-CTG, CADD 26.00
- E45K (p.Glu45Lys), gnomAD rs1356436410, REVEL 0.03, CADD 16.80
- E45D (p.Glu45Asp), gnomAD 1-11858467-C-A, REVEL 0.02, CADD 14.10
- E45E (p.Glu45Glu), rs1645134524, gnomAD 1-11858467-C-T, CADD 3.48
- E45G (p.Glu45Gly), gnomAD 1-11858468-T-C, REVEL 0.03, CADD 22.60
- E45* (p.Glu45Ter), gnomAD 1-11858469-C-A, CADD 40.00
- Q46H (p.Gln46His), gnomAD 1-11858464-C-A, REVEL 0.06, CADD 16.40
- Q46* (p.Gln46Ter), gnomAD 1-11858466-G-A, CADD 36.00
- R47C (p.Arg47Cys), rs777621972, NCI-TCGA Cosmic COSV6468, ExAC rs777621972, TOPMed rs777621972, REVEL 0.05, CADD 21.20, Variant assessed as somatic; moderate impact.
- R47H (p.Arg47His), rs5229, UniProt VAR 014581, 1000Genomes rs5229, ESP rs5229, REVEL 0.02, CADD 6.52
- R47L (p.Arg47Leu), gnomAD 1-11858462-C-A, REVEL 0.01, CADD 0.11
- R47S (p.Arg47Ser), gnomAD 1-11858463-G-T, REVEL 0.02, CADD 13.70
- N48D (p.Asn48Asp), gnomAD rs1645134404, REVEL 0.04, CADD 1.09
- N48K (p.Asn48Lys), TOPMed rs935981602, gnomAD rs935981602, REVEL 0.01, CADD 3.39
- N48S (p.Asn48Ser), TOPMed rs1645134397
- N48N (p.Asn48Asn), rs935981602, gnomAD 1-11858458-G-A, CADD 1.84
- H49Y (p.His49Tyr), gnomAD rs1645134371, REVEL 0.06, CADD 6.76
- H49H (p.His49His), rs1339530531, gnomAD 1-11858455-A-G, CADD 0.67
- H49D (p.His49Asp), gnomAD 1-11858457-G-C, REVEL 0.07, CADD 9.22
- L50F (p.Leu50Phe), rs371722685, ClinGen CA597244, ClinVar RCV004491082, ESP rs371722685, REVEL 0.11, CADD 14.80, Uncertain significance, not specified
- Q51R (p.Gln51Arg), gnomAD 1-11858450-T-C, REVEL 0.01, CADD 0.03
- G52G (p.Gly52Gly), gnomAD 1-11858446-G-T, CADD 3.34
- G52D (p.Gly52Asp), gnomAD 1-11858447-C-T, REVEL 0.03, CADD 0.07
- G52V (p.Gly52Val), gnomAD 1-11858447-C-A, REVEL 0.03, CADD 1.43
- G52S (p.Gly52Ser), gnomAD 1-11858448-C-T, REVEL 0.04, CADD 9.25
- L54Q (p.Leu54Gln), TOPMed rs1645134332, REVEL 0.10, CADD 19.80
- L54L (p.Leu54Leu), rs1163367379, gnomAD 1-11858440-C-T, CADD 0.70
- S55* (p.Ser55Ter), gnomAD rs1412033325, CADD 33.00
- S55P (p.Ser55Pro), TOPMed rs1203310170, gnomAD rs1203310170, REVEL 0.06, CADD 6.63
- S55S (p.Ser55Ser), rs570257248, gnomAD 1-11858437-C-T, CADD 0.18
- S55L (p.Ser55Leu), gnomAD 1-11858438-G-A, REVEL 0.04, CADD 2.50
- E56K (p.Glu56Lys), NCI-TCGA Cosmic COSV6468, Variant assessed as somatic; moderate impact.
- E56D (p.Glu56Asp), gnomAD 1-11858434-C-A, REVEL 0.06, CADD 21.00
- E56E (p.Glu56Glu), rs755267902, gnomAD 1-11858434-C-T, CADD 7.75
- E56G (p.Glu56Gly), gnomAD 1-11858435-T-C, REVEL 0.07, CADD 21.60
- L57L (p.Leu57Leu), gnomAD 1-11858431-C-T, CADD 5.33
- L57M (p.Leu57Met), gnomAD 1-11858433-G-T, REVEL 0.08, CADD 8.76
- Q58Q (p.Gln58Gln), gnomAD 1-11858428-C-T, CADD 3.72
- Q58H (p.Gln58His), gnomAD 1-11858428-C-A, REVEL 0.09, CADD 19.50
- Q58R (p.Gln58Arg), gnomAD 1-11858429-T-C, REVEL 0.09, CADD 21.70
- V59A (p.Val59Ala), NCI-TCGA Cosmic COSV1009, Variant assessed as somatic; moderate impact.
- V59G (p.Val59Gly), gnomAD rs1570558629, REVEL 0.02, CADD 5.98
- V59M (p.Val59Met), 1000Genomes rs550521638, ExAC rs550521638, gnomAD rs550521638, REVEL 0.10, CADD 10.40
- E60* (p.Glu60Ter), NCI-TCGA Cosmic COSV6468, CADD 33.00, Variant assessed as somatic; high impact.
- E60A (p.Glu60Ala), Ensembl rs1570558624
- E60E (p.Glu60Glu), rs1645134234, gnomAD 1-11858422-C-T, CADD 4.17
- E60D (p.Glu60Asp), gnomAD 1-11858422-C-A, REVEL 0.11, CADD 14.80
- E60V (p.Glu60Val), gnomAD 1-11858423-T-A, REVEL 0.06, CADD 19.40
- Q61E (p.Gln61Glu), TOPMed rs1392899491, gnomAD rs1392899491, REVEL 0.04, CADD 7.98
- Q61H (p.Gln61His), Ensembl rs977419475, REVEL 0.02, CADD 12.00
- T62I (p.Thr62Ile), NCI-TCGA Cosmic COSV6468, Variant assessed as somatic; moderate impact.
- T62P (p.Thr62Pro), TOPMed rs1645134193, REVEL 0.00, CADD 0.10
- T62R (p.Thr62Arg), ExAC rs780422182, TOPMed rs780422182, gnomAD rs780422182, REVEL 0.03, CADD 0.24, Uncertain significance, not specified
- T62T (p.Thr62Thr), gnomAD 1-11858416-T-A, CADD 3.38
- S63F (p.Ser63Phe), rs570474795, ClinGen CA18018171, ClinVar RCV004263373, TOPMed rs570474795, REVEL 0.04, CADD 6.33, Uncertain significance, not specified
- S63S (p.Ser63Ser), rs1412928912, gnomAD 1-11858413-G-T, CADD 1.17
- S63P (p.Ser63Pro), gnomAD 1-11858415-A-G, REVEL 0.04, CADD 0.06
- S63T (p.Ser63Thr), gnomAD 1-11858415-A-T, REVEL 0.00, CADD 0.00
- L64L (p.Leu64Leu), rs756208728, gnomAD 1-11858410-C-T, CADD 4.20
- L64P (p.Leu64Pro), gnomAD 1-11858411-A-G, REVEL 0.04, CADD 1.18
- L64R (p.Leu64Arg), gnomAD 1-11858411-A-C, REVEL 0.05, CADD 0.61
- E65D (p.Glu65Asp), gnomAD rs1473441019, REVEL 0.07, CADD 7.71
- E65del (p.Glu65del), gnomAD 1-11858406-GCTC-G, CADD 7.20
- E65S (p.Glu65Ser), gnomAD 1-11858408-TC-T, CADD 20.90
- P66L (p.Pro66Leu), TOPMed rs1280392538, gnomAD rs1280392538
- P66R (p.Pro66Arg), TOPMed rs1280392538, gnomAD rs1280392538, REVEL 0.07, CADD 21.30
- P66H (p.Pro66His), gnomAD 1-11858405-G-T, REVEL 0.08, CADD 21.50
- P66S (p.Pro66Ser), gnomAD 1-11858406-G-A, REVEL 0.08, CADD 5.00
- P66T (p.Pro66Thr), gnomAD 1-11858406-G-T, REVEL 0.03, CADD 3.52
- L67F (p.Leu67Phe), ExAC rs750491009, gnomAD rs750491009, REVEL 0.02, CADD 10.40
- L67S (p.Leu67Ser), gnomAD 1-11858402-AG-A, CADD 21.70
- L67P (p.Leu67Pro), gnomAD 1-11858402-A-AG, CADD 21.90
- Q68* (p.Gln68Ter), 1000Genomes rs528896640, TOPMed rs528896640, CADD 34.00
- E69D (p.Glu69Asp), 1000Genomes rs74613227, ESP rs74613227, ExAC rs74613227, TOPMed rs74613227, REVEL 0.02, CADD 8.64, Uncertain significance, not specified
- E69E (p.Glu69Glu), gnomAD 1-11858395-C-T, CADD 1.17
- E69G (p.Glu69Gly), gnomAD 1-11858396-T-C, REVEL 0.04, CADD 13.70
- E69K (p.Glu69Lys), gnomAD 1-11858397-C-T, REVEL 0.01, CADD 3.46
- S70S (p.Ser70Ser), rs1452126623, gnomAD 1-11858392-G-A, CADD 2.43
- S70N (p.Ser70Asn), gnomAD 1-11858393-C-T, REVEL 0.03, CADD 0.03
- S70I (p.Ser70Ile), gnomAD 1-11858393-C-A, REVEL 0.02, CADD 1.55
- P71T (p.Pro71Thr), gnomAD rs1268785989, REVEL 0.04, CADD 3.38
- P71H (p.Pro71His), gnomAD 1-11858390-G-T, REVEL 0.01, CADD 0.02
- P71R (p.Pro71Arg), gnomAD 1-11858390-G-C, REVEL 0.00, CADD 0.00
- P71S (p.Pro71Ser), gnomAD 1-11858391-G-A, REVEL 0.04, CADD 4.61
- R72C (p.Arg72Cys), ExAC rs762337879, TOPMed rs762337879, gnomAD rs762337879, REVEL 0.08, CADD 11.60
- R72G (p.Arg72Gly), ExAC rs762337879, TOPMed rs762337879, gnomAD rs762337879, REVEL 0.02, CADD 0.09, Likely benign, not specified
- R72H (p.Arg72His), rs61761991, ClinGen CA597234, ClinVar RCV000895831, 1000Genomes rs61761991, REVEL 0.01, CADD 0.17, Benign, not provided
Public NPPB analysis runs
- NPPB analysis run — NPPB (351 variants) — completed 2026-08-21