NPR1 (P16066) variants and mutations
NPR1 (also known as P16066) is a human protein-coding gene encoding an atrial natriuretic peptide receptor 1 protein. It converts natriuretic-peptide binding into intracellular cyclic GMP production, mediating vasodilation, natriuresis, and antihypertrophic cardiac effects. Loss-of-function variation can raise blood pressure and blunt natriuretic signaling, whereas enhanced pathway activity is cardioprotective. This analysis covers 1,658 NPR1 variants and mutations. Of these, 82% have computational variant effect predictions. Disease context includes congestive heart failure, hypertensive disorder, and cardiovascular disorder. Example NPR1 variants include P2L, P2T, and P2S.
Variant analysis overview
- Gene: NPR1
- Protein: P16066
- UniProt accession: P16066
- Organism: Homo sapiens
- Variants analyzed: 1658
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 1,114 unspecified-consequence records; 33 frameshift variants; 355 missense variants; 136 synonymous variants; 8 in-frame deletions; 2 in-frame insertions; 13 stop-gained variants
- Prediction scores: 1,359 variants have prediction scores (82% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: congestive heart failure, hypertensive disorder, cardiovascular disorder, heart failure, Increased blood pressure, Dyspnea, myocardial ischemia, impaired renal function disease, heart disorder, Respiratory distress, essential hypertension, neurodegenerative disease.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 2 domains; 3 binding sites; 14 post-translational modification sites.
- Structural context: 433 variants have structural context.
- PTM context: 22 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable NPR1 variants
Examples include P2L, P2T, P2S, P2Q, P2P, G3W, G3R, G3A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P2L (p.Pro2Leu), 1000Genomes rs13305995, ExAC rs13305995, TOPMed rs13305995, gnomAD rs13305995, REVEL 0.20, CADD 12.30
- P2T (p.Pro2Thr), gnomAD rs1669681743, REVEL 0.23, CADD 16.00
- P2S (p.Pro2Ser), gnomAD 1-153679112-C-T, REVEL 0.23, CADD 16.60
- P2Q (p.Pro2Gln), gnomAD 1-153679113-C-A, REVEL 0.15, CADD 11.10
- P2P (p.Pro2Pro), rs1309229148, gnomAD 1-153679114-G-C, CADD 5.49
- G3W (p.Gly3Trp), gnomAD 1-153679115-G-T, REVEL 0.25, CADD 8.67
- G3R (p.Gly3Arg), gnomAD 1-153679115-G-A, REVEL 0.20, CADD 2.92
- G3A (p.Gly3Ala), gnomAD 1-153679116-G-C, REVEL 0.14, CADD 1.25
- G3E (p.Gly3Glu), gnomAD 1-153679116-G-A, REVEL 0.14, CADD 1.39
- G3G (p.Gly3Gly), rs774887934, gnomAD 1-153679117-G-T, CADD 5.98
- P4R (p.Pro4Arg), Ensembl rs1301304324
- P4S (p.Pro4Ser), TOPMed rs1264744512, gnomAD rs1264744512, REVEL 0.21, CADD 9.86
- P4T (p.Pro4Thr), gnomAD 1-153679118-C-A, REVEL 0.19, CADD 9.68
- P4P (p.Pro4Pro), gnomAD 1-153679120-C-T, CADD 9.03
- R5Q (p.Arg5Gln), TOPMed rs1489803000, gnomAD rs1489803000, REVEL 0.19, CADD 16.40
- R5W (p.Arg5Trp), NCI-TCGA TCGA novel, REVEL 0.22, CADD 21.70, Variant assessed as somatic; moderate impact.
- R5G (p.Arg5Gly), rs1669682199, gnomAD 1-153679113-CG-C, CADD 14.80
- R5L (p.Arg5Leu), gnomAD 1-153679122-G-T, REVEL 0.25, CADD 16.90
- R5R (p.Arg5Arg), gnomAD 1-153679123-G-T, CADD 10.00
- R6L (p.Arg6Leu), rs543746764, ClinGen CA30731256, ClinVar RCV004289640, 1000Genomes rs543746764, REVEL 0.16, CADD 18.30, Uncertain significance, not specified
- R6S (p.Arg6Ser), 1000Genomes rs13305996, ExAC rs13305996, TOPMed rs13305996, gnomAD rs13305996, REVEL 0.12, CADD 14.90
- R6G (p.Arg6Gly), gnomAD 1-153679111-G-GCC, CADD 23.90
- R6W (p.Arg6Trp), gnomAD 1-153679116-GGCCC, CADD 23.50
- R6C (p.Arg6Cys), gnomAD 1-153679124-C-T, REVEL 0.10, CADD 17.30
- R6H (p.Arg6His), gnomAD 1-153679125-G-A, REVEL 0.13, CADD 18.60
- R6R (p.Arg6Arg), gnomAD 1-153679126-C-T, CADD 13.10
- P7H (p.Pro7His), rs891868440, ClinGen CA30731265, ClinVar RCV004491096, TOPMed rs891868440, REVEL 0.27, CADD 16.80, Uncertain significance, not specified
- P7L (p.Pro7Leu), TOPMed rs891868440, gnomAD rs891868440, REVEL 0.26, CADD 16.60, Uncertain significance
- P7S (p.Pro7Ser), TOPMed rs1052318333, gnomAD rs1052318333, REVEL 0.21, CADD 14.10
- P7W (p.Pro7Trp), gnomAD 1-153679126-C-CTG, CADD 22.90
- P7T (p.Pro7Thr), gnomAD 1-153679127-C-A, REVEL 0.20, CADD 13.50
- P7R (p.Pro7Arg), gnomAD 1-153679128-C-G, REVEL 0.20, CADD 13.80
- P7P (p.Pro7Pro), gnomAD 1-153679129-C-A, CADD 9.99
- A8G (p.Ala8Gly), TOPMed rs1161031173, gnomAD rs1161031173, REVEL 0.21, CADD 12.00, Uncertain significance, not specified
- A8P (p.Ala8Pro), ExAC rs767857443, gnomAD rs767857443, REVEL 0.17, CADD 9.33
- A8S (p.Ala8Ser), NCI-TCGA Cosmic COSV6414, REVEL 0.18, CADD 4.22, Variant assessed as somatic; moderate impact.
- A8T (p.Ala8Thr), ExAC rs767857443, gnomAD rs767857443, REVEL 0.20, CADD 7.13
- A8L (p.Ala8Leu), gnomAD 1-153679125-GC-G, CADD 22.90
- A8D (p.Ala8Asp), gnomAD 1-153679131-C-A, REVEL 0.20, CADD 13.50
- A8V (p.Ala8Val), gnomAD 1-153679131-C-T, REVEL 0.20, CADD 11.10
- A8A (p.Ala8Ala), gnomAD 1-153679132-T-C, CADD 11.80
- G9C (p.Gly9Cys), gnomAD 1-153679133-G-T, REVEL 0.22, CADD 22.20
- G9S (p.Gly9Ser), gnomAD 1-153679133-G-A, REVEL 0.20, CADD 21.60
- G9D (p.Gly9Asp), gnomAD 1-153679134-G-A, REVEL 0.24, CADD 23.00
- G9V (p.Gly9Val), gnomAD 1-153679134-G-T, REVEL 0.20, CADD 23.00
- G9G (p.Gly9Gly), gnomAD 1-153679135-C-A, CADD 13.30
- S10C (p.Ser10Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S10F (p.Ser10Phe), TOPMed rs1669683617, REVEL 0.24, CADD 18.40
- S10P (p.Ser10Pro), Ensembl rs1669683542, REVEL 0.26, CADD 18.30
- S10S (p.Ser10Ser), rs752716418, gnomAD 1-153679138-C-T, CADD 12.10
- R11C (p.Arg11Cys), TOPMed rs1417422135, gnomAD rs1417422135, REVEL 0.23, CADD 22.70
- R11H (p.Arg11His), TOPMed rs904927899, gnomAD rs904927899, REVEL 0.23, CADD 21.10
- R11L (p.Arg11Leu), TOPMed rs904927899, gnomAD rs904927899, REVEL 0.20, CADD 20.60, Uncertain significance, not specified
- R11S (p.Arg11Ser), TOPMed rs1417422135, gnomAD rs1417422135, REVEL 0.17, CADD 21.20
- R11R (p.Arg11Arg), rs1281312830, gnomAD 1-153679141-C-T, CADD 12.80
- L12M (p.Leu12Met), gnomAD rs1171762496, REVEL 0.08, CADD 13.40
- L12P (p.Leu12Pro), gnomAD 1-153679143-T-C, REVEL 0.19, CADD 14.90
- L12L (p.Leu12Leu), gnomAD 1-153679144-G-T, CADD 10.90
- R13C (p.Arg13Cys), TOPMed rs1001658927, gnomAD rs1001658927, REVEL 0.30, CADD 22.10
- R13L (p.Arg13Leu), ExAC rs13305997, TOPMed rs13305997, gnomAD rs13305997, REVEL 0.29, CADD 14.00
- R13P (p.Arg13Pro), ExAC rs13305997, TOPMed rs13305997, gnomAD rs13305997, REVEL 0.48, CADD 15.50
- R13S (p.Arg13Ser), TOPMed rs1001658927, gnomAD rs1001658927, REVEL 0.27, CADD 14.60
- R13H (p.Arg13His), gnomAD 1-153679146-G-A, REVEL 0.29, CADD 15.10
- R13R (p.Arg13Arg), rs1669684222, gnomAD 1-153679147-C-A, CADD 12.00
- L14M (p.Leu14Met), gnomAD 1-153679148-C-A, REVEL 0.26, CADD 22.80
- L14L (p.Leu14Leu), gnomAD 1-153679148-C-T, CADD 12.00
- L14P (p.Leu14Pro), gnomAD 1-153679149-T-C, REVEL 0.42, CADD 21.00
- L15P (p.Leu15Pro), ExAC rs765066553, TOPMed rs765066553, gnomAD rs765066553, REVEL 0.28, CADD 20.50
- L15I (p.Leu15Ile), gnomAD 1-153679151-C-A, REVEL 0.23, CADD 12.50
- L15F (p.Leu15Phe), gnomAD 1-153679151-C-T, REVEL 0.23, CADD 14.10
- L15R (p.Leu15Arg), gnomAD 1-153679152-T-G, REVEL 0.32, CADD 19.90
- L15L (p.Leu15Leu), gnomAD 1-153679153-C-A, CADD 8.59
- L16M (p.Leu16Met), gnomAD 1-153679154-C-A, REVEL 0.19, CADD 16.60
- L16L (p.Leu16Leu), gnomAD 1-153679154-C-T, CADD 12.10
- L16P (p.Leu16Pro), gnomAD 1-153679155-T-C, REVEL 0.28, CADD 20.80
- L17P (p.Leu17Pro), Ensembl rs1669684528
- L17I (p.Leu17Ile), gnomAD 1-153679157-C-A, REVEL 0.29, CADD 14.20
- L17F (p.Leu17Phe), gnomAD 1-153679157-C-T, REVEL 0.27, CADD 15.70
- L17L (p.Leu17Leu), gnomAD 1-153679159-C-A, CADD 7.33
- L18L (p.Leu18Leu), rs1365873061, gnomAD 1-153679160-C-T, CADD 7.38
- L18M (p.Leu18Met), gnomAD 1-153679160-C-A, REVEL 0.26, CADD 8.20
- L18P (p.Leu18Pro), gnomAD 1-153679161-T-C, REVEL 0.29, CADD 16.30
- p.Leu19 Leu20del, rs1021769501, gnomAD 1-153679146-GCCTG, CADD 15.00
- L19C (p.Leu19Cys), gnomAD 1-153679161-TG-T, CADD 21.70
- L19M (p.Leu19Met), gnomAD 1-153679163-C-A, REVEL 0.22, CADD 15.30
- L19L (p.Leu19Leu), gnomAD 1-153679163-C-T, CADD 9.59
- L20P (p.Leu20Pro), Ensembl rs1571343228, REVEL 0.26, CADD 15.60
- p.Leu20dup, gnomAD 1-153679159-C-CCT, CADD 10.50
- L20del (p.Leu20del), rs1669684696, gnomAD 1-153679159-CCTG-, CADD 11.60
- L20L (p.Leu20Leu), gnomAD 1-153679166-C-T, CADD 9.27
- P21L (p.Pro21Leu), TOPMed rs1669685011, REVEL 0.19, CADD 8.89
- p.Pro21 Leu26del, gnomAD 1-153679159-CCTGC, CADD 13.40
- P21T (p.Pro21Thr), gnomAD 1-153679169-C-A, REVEL 0.20, CADD 8.44
- P21S (p.Pro21Ser), gnomAD 1-153679169-C-T, REVEL 0.19, CADD 10.10
- P21Q (p.Pro21Gln), gnomAD 1-153679170-C-A, REVEL 0.17, CADD 10.60
- P21R (p.Pro21Arg), gnomAD 1-153679170-C-G, REVEL 0.21, CADD 10.90
- P21P (p.Pro21Pro), gnomAD 1-153679171-G-A, CADD 9.51
- P22L (p.Pro22Leu), TOPMed rs1281961171, gnomAD rs1281961171, REVEL 0.18, CADD 6.41
- P22del (p.Pro22del), rs1557958885, gnomAD 1-153679167-TGCC-, CADD 10.80
- P22S (p.Pro22Ser), gnomAD 1-153679172-C-T, REVEL 0.09, CADD 9.00
- P22Q (p.Pro22Gln), gnomAD 1-153679173-C-A, REVEL 0.12, CADD 7.41
- P22P (p.Pro22Pro), gnomAD 1-153679174-G-T, CADD 8.48
- L23P (p.Leu23Pro), rs994822671, NCI-TCGA Cosmic COSV6414, TOPMed rs994822671, gnomAD rs994822671, REVEL 0.23, CADD 13.50, Variant assessed as somatic; moderate impact.
- L23R (p.Leu23Arg), TOPMed rs994822671, gnomAD rs994822671
- L23V (p.Leu23Val), TOPMed rs1669685315
- L23M (p.Leu23Met), gnomAD 1-153679175-C-A, REVEL 0.19, CADD 11.00
- L23L (p.Leu23Leu), gnomAD 1-153679175-C-T, CADD 8.18
- L24L (p.Leu24Leu), gnomAD 1-153679178-C-T, CADD 8.25
- L24M (p.Leu24Met), gnomAD 1-153679178-C-A, REVEL 0.29, CADD 16.80
- L24P (p.Leu24Pro), gnomAD 1-153679179-T-C, REVEL 0.55, CADD 22.50
- L25M (p.Leu25Met), gnomAD 1-153679181-C-A, REVEL 0.29, CADD 19.50
- L25L (p.Leu25Leu), gnomAD 1-153679181-C-T, CADD 9.07
- L26L (p.Leu26Leu), gnomAD 1-153679184-C-T, CADD 8.84
- L26M (p.Leu26Met), gnomAD 1-153679184-C-A, REVEL 0.23, CADD 14.90
- L26P (p.Leu26Pro), gnomAD 1-153679185-T-C, REVEL 0.29, CADD 19.00
- L27F (p.Leu27Phe), gnomAD rs1311925093, REVEL 0.26, CADD 19.50
- L27P (p.Leu27Pro), gnomAD rs1357183087, REVEL 0.17, CADD 17.90
- L27del (p.Leu27del), rs774440887, gnomAD 1-153679173-CGCT-, CADD 11.40
- p.Leu27dup, rs774440887, gnomAD 1-153679173-C-CGC, CADD 11.20
- L27I (p.Leu27Ile), gnomAD 1-153679187-C-A, REVEL 0.23, CADD 15.30
- L27L (p.Leu27Leu), gnomAD 1-153679189-C-A, CADD 9.16
- R28Q (p.Arg28Gln), TOPMed rs1292195838, gnomAD rs1292195838, REVEL 0.18, CADD 8.77, Uncertain significance, not specified
- R28W (p.Arg28Trp), TOPMed rs1669685732, REVEL 0.30, CADD 21.20
- R28G (p.Arg28Gly), gnomAD 1-153679188-TCC-T, CADD 23.50
- R28R (p.Arg28Arg), gnomAD 1-153679190-C-A, CADD 8.97
- R28L (p.Arg28Leu), gnomAD 1-153679191-G-T, REVEL 0.20, CADD 9.39
- R28P (p.Arg28Pro), gnomAD 1-153679191-G-C, REVEL 0.21, CADD 10.30
- G29D (p.Gly29Asp), 1000Genomes rs1215380888, TOPMed rs1215380888, gnomAD rs1215380888, REVEL 0.20, CADD 9.76
- G29S (p.Gly29Ser), Ensembl rs1571343280, REVEL 0.18, CADD 13.40
- G29A (p.Gly29Ala), rs1247967845, gnomAD 1-153679190-CG-C, CADD 17.40
- G29C (p.Gly29Cys), gnomAD 1-153679193-G-T, REVEL 0.27, CADD 21.70
- G29V (p.Gly29Val), gnomAD 1-153679194-G-T, REVEL 0.20, CADD 11.70
- G29G (p.Gly29Gly), gnomAD 1-153679195-C-A, CADD 8.45
- S30N (p.Ser30Asn), Ensembl rs1571343294, REVEL 0.15, CADD 7.32
- S30G (p.Ser30Gly), gnomAD 1-153679196-A-G, REVEL 0.12, CADD 6.60
- S30T (p.Ser30Thr), gnomAD 1-153679197-G-C, REVEL 0.16, CADD 6.31
- S30I (p.Ser30Ile), gnomAD 1-153679197-G-T, REVEL 0.16, CADD 11.20
- S30R (p.Ser30Arg), gnomAD 1-153679198-C-A, REVEL 0.20, CADD 14.40
- S30S (p.Ser30Ser), rs1240528120, gnomAD 1-153679198-C-T, CADD 9.68
- H31Q (p.His31Gln), 1000Genomes rs562076362, TOPMed rs562076362, gnomAD rs562076362, REVEL 0.13, CADD 3.88
- H31R (p.His31Arg), gnomAD rs1486898896, REVEL 0.16, CADD 1.82
- H31Y (p.His31Tyr), gnomAD 1-153679199-C-T, REVEL 0.22, CADD 0.40
- H31N (p.His31Asn), gnomAD 1-153679199-C-A, REVEL 0.14, CADD 1.28
- H31H (p.His31His), rs562076362, gnomAD 1-153679201-C-T, CADD 5.59
- A32E (p.Ala32Glu), TOPMed rs1669686766, REVEL 0.27, CADD 13.60
- A32T (p.Ala32Thr), TOPMed rs1243141793, gnomAD rs1243141793, REVEL 0.18, CADD 15.10
- A32V (p.Ala32Val), NCI-TCGA TCGA novel, REVEL 0.16, CADD 15.40, Variant assessed as somatic; moderate impact.
- A32S (p.Ala32Ser), gnomAD 1-153679202-G-T, REVEL 0.14, CADD 12.40
- A32A (p.Ala32Ala), rs1405227266, gnomAD 1-153679204-G-A, CADD 6.35
- G33D (p.Gly33Asp), TOPMed rs1669686966, REVEL 0.08, CADD 9.35
- G33C (p.Gly33Cys), gnomAD 1-153679205-G-T, REVEL 0.17, CADD 16.90
- G33S (p.Gly33Ser), gnomAD 1-153679205-G-A, REVEL 0.03, CADD 11.50
- G33V (p.Gly33Val), gnomAD 1-153679206-G-T, REVEL 0.11, CADD 10.50
- G33G (p.Gly33Gly), gnomAD 1-153679207-C-T, CADD 7.68
- N34K (p.Asn34Lys), TOPMed rs1443313649, gnomAD rs1443313649, REVEL 0.11, CADD 17.60
- N34S (p.Asn34Ser), rs1174456586, gnomAD rs1174456586, REVEL 0.08, CADD 18.40, Variant assessed as somatic; moderate impact.
- N34N (p.Asn34Asn), rs1443313649, gnomAD 1-153679210-C-T, CADD 8.11
- L35P (p.Leu35Pro), NCI-TCGA TCGA novel, REVEL 0.65, CADD 24.50, Variant assessed as somatic; moderate impact.
- L35M (p.Leu35Met), gnomAD 1-153679211-C-A, REVEL 0.34, CADD 22.90
- L35L (p.Leu35Leu), gnomAD 1-153679211-C-T, CADD 8.86
- T36P (p.Thr36Pro), gnomAD 1-153679212-TGACG, CADD 25.30
- T36S (p.Thr36Ser), gnomAD 1-153679214-A-T, REVEL 0.33, CADD 20.60
- T36A (p.Thr36Ala), gnomAD 1-153679214-A-G, REVEL 0.39, CADD 21.70
- T36K (p.Thr36Lys), gnomAD 1-153679215-C-A, REVEL 0.46, CADD 19.80
- T36M (p.Thr36Met), gnomAD 1-153679215-C-T, REVEL 0.48, CADD 22.90
- T36T (p.Thr36Thr), rs1386282300, gnomAD 1-153679216-G-A, CADD 2.39
- V37I (p.Val37Ile), gnomAD 1-153679217-G-A, REVEL 0.10, CADD 10.30
- V37L (p.Val37Leu), gnomAD 1-153679217-G-T, REVEL 0.17, CADD 7.43
- V37A (p.Val37Ala), gnomAD 1-153679218-T-C, REVEL 0.31, CADD 22.10
- V37V (p.Val37Val), gnomAD 1-153679219-A-G, CADD 10.70
- A38V (p.Ala38Val), gnomAD rs1400441329, REVEL 0.52, CADD 23.10
- A38S (p.Ala38Ser), gnomAD 1-153679220-G-T, REVEL 0.50, CADD 25.20
- A38D (p.Ala38Asp), gnomAD 1-153679221-C-A, REVEL 0.65, CADD 24.80
- A38A (p.Ala38Ala), rs750418293, gnomAD 1-153679222-C-T, CADD 10.50
- V39L (p.Val39Leu), gnomAD 1-153679223-G-T, REVEL 0.28, CADD 23.20
- V39M (p.Val39Met), gnomAD 1-153679223-G-A, REVEL 0.42, CADD 25.40
- V39A (p.Val39Ala), gnomAD 1-153679224-T-C, REVEL 0.22, CADD 22.20
- V39V (p.Val39Val), rs2101726327, gnomAD 1-153679225-G-C, CADD 11.40
- p.Val40 Leu43del, gnomAD 1-153679223-GTGGT, CADD 19.40
- V40Y (p.Val40Tyr), gnomAD 1-153679224-TG-T, CADD 25.80
Public NPR1 analysis runs
- NPR1 analysis run — NPR1 (1,658 variants) — completed 2026-08-22