Details for: NPR1

Gene ID: 4881

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: NPR1

Ensembl ID: ENSG00000169418

Description: natriuretic peptide receptor 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • podocyte CL0000653
    CSI 5.31
    rCSI 23.6%
    PRS 90.5
  • endothelial cell of vascular tree CL0002139
    CSI 3.59
    rCSI 19.63%
    PRS 86.39
  • blood vessel endothelial cell CL0000071
    CSI 3.37
    rCSI 7%
    PRS 88.19
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.94
    rCSI 4.17%
    PRS 87.58
  • pulmonary capillary endothelial cell CL4028001
    CSI 2.93
    rCSI 5.59%
    PRS 95.31
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.81
    rCSI 2.71%
    PRS 88.58
  • alveolar adventitial fibroblast CL4028006
    CSI 2.68
    rCSI 4.23%
    PRS 90.87
  • pulmonary artery endothelial cell CL1001568
    CSI 2.57
    rCSI 3.5%
    PRS 94.37
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 2.53
    rCSI 7.81%
    PRS 91.88
  • ependymal cell CL0000065
    CSI 2.4
    rCSI 4.88%
    PRS 72.17
  • endothelial cell of periportal hepatic sinusoid CL0019021
    CSI 2.38
    rCSI 10.91%
    PRS 92.04
  • renal interstitial pericyte CL1001318
    CSI 1.9
    rCSI 5.23%
    PRS 87.14
  • endocardial cell CL0002350
    CSI 1.81
    rCSI 8.65%
    PRS 86.26
  • parietal epithelial cell CL1000452
    CSI 1.61
    rCSI 4.31%
    PRS 84.38
  • epicardial adipocyte CL1000309
    CSI 1.11
    rCSI 3.62%
    PRS 87.41
  • lung microvascular endothelial cell CL2000016
    CSI 0.46
    rCSI 8.98%
    PRS 94.08
  • vein endothelial cell of respiratory system CL4033008
    CSI 0.44
    rCSI 3%
    PRS 93.21

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [NPR1](/details-gene/4881), or natriuretic peptide receptor 1, encodes the atrial natriuretic peptide receptor type A (ANP-A), a key cell surface receptor integral to cardiovascular and renal homeostasis. As a guanylate cyclase-coupled receptor, it binds natriuretic peptides, leading to the production of cyclic GMP (cGMP) and subsequent downstream signaling. This pathway is centrally involved in the [regulation of blood pressure](/details-go/GO:0008217), [body fluid secretion](/details-go/GO:0007589), and vascular tone. **Overall**, expression data reveals that [NPR1](/details-gene/4881) is a highly significant marker for specialized cells involved in filtration and fluid exchange, with its most pronounced significance observed in [podocyte](/details-cell/CL0000653)s of the kidney and various types of [endothelial cell](/details-cell/CL0002139)s. Its critical role in these processes is underscored by its clinical association with cardiovascular health ([108960](https://omim.org/entry/108960)). ## Cellular Roles and Expression Landscape The expression profile of [NPR1](/details-gene/4881) highlights its specialized function in the regulation of fluid dynamics and vascular function across different organ systems. The gene's highest significance is in [podocyte](/details-cell/CL0000653)s (CSI: 5.31), the specialized cells that form the glomerular filtration barrier in the kidney, which is consistent with its role in regulating renal sodium and water excretion. A broader analysis of its expression reveals a strong enrichment in two primary functional cell clusters: * **Renal Epithelium and Associated Cells:** Beyond [podocyte](/details-cell/CL0000653)s, [NPR1](/details-gene/4881) shows significant expression in the [kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111), [parietal epithelial cell](/details-cell/CL1000452), and [renal interstitial pericyte](/details-cell/CL1001318). This pattern suggests a coordinated role for [NPR1](/details-gene/4881) signaling across multiple segments of the nephron and renal interstitium to control diuresis and natriuresis. * **Vascular Endothelium:** The gene is a significant marker across a wide array of endothelial cells, including [endothelial cell of vascular tree](/details-cell/CL0002139), [blood vessel endothelial cell](/details-cell/CL0000071), [pulmonary capillary endothelial cell](/details-cell/CL4028001), and [pulmonary artery endothelial cell](/details-cell/CL1001568). This widespread endothelial expression supports its function in maintaining vascular tone, regulating permeability, and mediating vasodilation in response to natriuretic peptides. Notably, significant expression is also observed in other secretory or barrier cells, such as [fallopian tube secretory epithelial cell](/details-cell/CL4030006) and [ependymal cell](/details-cell/CL0000065), suggesting that its role in cGMP-mediated fluid regulation may extend to reproductive and central nervous system physiology. ## Pathways and Molecular Function The molecular functions and biological pathways associated with [NPR1](/details-gene/4881) are tightly linked to its identity as a receptor guanylyl cyclase. Its primary molecular function is [natriuretic peptide receptor activity](/details-go/GO:0016941), which upon binding peptide hormones like atrial natriuretic peptide (ANP), activates its intrinsic [guanylate cyclase activity](/details-go/GO:0004383). This catalytic action converts GTP to cGMP, initiating the [cGMP-mediated signaling](/details-go/GO:0019934) pathway, a mechanism first elucidated in early studies of the receptor [Link](https://doi.org/10.1002/j.1460-2075.1989.tb03518.x). This signaling cascade drives several critical biological processes consistent with the gene's cellular expression profile: * **Cardiovascular Regulation:** It is a central player in the [regulation of blood pressure](/details-go/GO:0008217), [blood vessel diameter maintenance](/details-go/GO:0097746), and the [negative regulation of smooth muscle cell proliferation](/details-go/GO:0048662). Its involvement in [cardiac conduction](/details-reactome/R-HSA-5576891) and [muscle contraction](/details-reactome/R-HSA-397014) is also annotated. * **Renal Function:** The receptor directly mediates the [positive regulation of renal sodium excretion](/details-go/GO:0035815) and the [positive regulation of urine volume](/details-go/GO:0035810), aligning with its high significance in kidney cell types. * **Cellular Localization:** As expected for a cell surface receptor, [NPR1](/details-gene/4881) is primarily localized to the [plasma membrane](/details-go/GO:0005886), where it forms a receptor complex ([ANPR-A receptor complex](/details-go/GO:1990620)) to transduce extracellular signals. ## Research Directions The highly specific expression pattern of [NPR1](/details-gene/4881) in critical physiological barrier cells, combined with its well-defined signaling mechanism, presents clear avenues for further investigation into its role in organ-specific pathologies. **Proposed Hypotheses:** 1. Given its premier significance in [podocyte](/details-cell/CL0000653)s, dysfunction in local [NPR1](/details-gene/4881) signaling may be a key, underappreciated factor in the pathogenesis of proteinuric kidney diseases, such as diabetic nephropathy or focal segmental glomerulosclerosis. Loss of this signaling may compromise the structural integrity of the glomerular filtration barrier independent of systemic blood pressure changes. 2. The high expression of [NPR1](/details-gene/4881) in specialized vascular beds, such as the [pulmonary capillary endothelial cell](/details-cell/CL4028001), suggests it plays a critical role in preventing tissue-specific edema. Dysregulation of [NPR1](/details-gene/4881) activity in the pulmonary vasculature could be a primary driver of non-cardiogenic pulmonary edema. **Experimental Approach to Test Hypothesis 1:** To directly test the role of podocyte-intrinsic [NPR1](/details-gene/4881) in maintaining the glomerular filtration barrier, a conditional knockout mouse model could be generated using Cre-LoxP technology with a podocyte-specific Cre driver (e.g., NPHS2-Cre). These mice would lack [NPR1](/details-gene/4881) exclusively in [podocyte](/details-cell/CL0000653)s. The experimental mice and control littermates could be subjected to models of kidney stress, such as streptozotocin-induced diabetes or angiotensin II-induced hypertension. Key readouts would include urinary albumin-to-creatinine ratio to assess proteinuria, measurement of glomerular filtration rate, and ultrastructural analysis of podocyte foot processes via transmission electron microscopy to detect effacement. **Therapeutic Potential:** [NPR1](/details-gene/4881) is a well-established therapeutic target, and the primary strategy is **activation**. Recombinant natriuretic peptides (e.g., nesiritide) are used clinically, but their use is limited by short half-life and systemic side effects like hypotension. The highly specific expression of [NPR1](/details-gene/4881) in cells like [podocyte](/details-cell/CL0000653)s suggests significant potential for developing novel agonists with improved pharmacokinetics or targeted delivery mechanisms. Such agents could offer a more focused therapeutic benefit for chronic kidney disease or conditions of localized fluid imbalance, potentially decoupling the desired renal or anti-fibrotic effects from dose-limiting systemic vasodilation.

Genular Protein ID: 972057719

Symbol: ANPRA_HUMAN

Name: Atrial natriuretic peptide receptor type A

UniProtKB Accession Codes:

P16066 B0ZBF0 Q5SR08 Q6P4Q3

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 3 CTD 1 ChEBI 6 ChEMBL 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 7 DrugCentral 1 EC 1 EMBL 8 Ensembl 1 ExpressionAtlas 1 GO 28 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 10 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2569967

Title: Human atrial natriuretic peptide receptor defines a new paradigm for second messenger signal transduction.

PubMed ID: 2569967

DOI: 10.1002/j.1460-2075.1989.tb03518.x

PubMed ID: 9618281

Title: Organization of the human natriuretic peptide receptor A gene.

PubMed ID: 9618281

DOI: 10.1006/bbrc.1998.8693

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 7954658

Title: Expression of mRNA for atrial natriuretic peptide receptor guanylate cyclase (ANPRA) in human retina.

PubMed ID: 7954658

DOI: 10.1007/bf02088585

PubMed ID: 1660465

Title: Extracellular domain-IgG fusion proteins for three human natriuretic peptide receptors. Hormone pharmacology and application to solid phase screening of synthetic peptide antisera.

PubMed ID: 1660465

DOI: 10.1016/s0021-9258(18)54463-x

PubMed ID: 1672777

Title: Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP).

PubMed ID: 1672777

DOI: 10.1126/science.1672777

PubMed ID: 20977274

Title: Mass spectrometric identification of phosphorylation sites in guanylyl cyclase A and B.

PubMed ID: 20977274

DOI: 10.1021/bi101700e

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 1061
  • Mass: 118919
  • Checksum: E6B5BD0FCA32F70D
  • Sequence:
    • MPGPRRPAGS RLRLLLLLLL PPLLLLLRGS HAGNLTVAVV LPLANTSYPW SWARVGPAVE 
LALAQVKARP DLLPGWTVRT VLGSSENALG VCSDTAAPLA AVDLKWEHNP AVFLGPGCVY 
AAAPVGRFTA HWRVPLLTAG APALGFGVKD EYALTTRAGP SYAKLGDFVA ALHRRLGWER 
QALMLYAYRP GDEEHCFFLV EGLFMRVRDR LNITVDHLEF AEDDLSHYTR LLRTMPRKGR 
VIYICSSPDA FRTLMLLALE AGLCGEDYVF FHLDIFGQSL QGGQGPAPRR PWERGDGQDV 
SARQAFQAAK IITYKDPDNP EYLEFLKQLK HLAYEQFNFT MEDGLVNTIP ASFHDGLLLY 
IQAVTETLAH GGTVTDGENI TQRMWNRSFQ GVTGYLKIDS SGDRETDFSL WDMDPENGAF 
RVVLNYNGTS QELVAVSGRK LNWPLGYPPP DIPKCGFDNE DPACNQDHLS TLEVLALVGS 
LSLLGILIVS FFIYRKMQLE KELASELWRV RWEDVEPSSL ERHLRSAGSR LTLSGRGSNY 
GSLLTTEGQF QVFAKTAYYK GNLVAVKRVN RKRIELTRKV LFELKHMRDV QNEHLTRFVG 
ACTDPPNICI LTEYCPRGSL QDILENESIT LDWMFRYSLT NDIVKGMLFL HNGAICSHGN 
LKSSNCVVDG RFVLKITDYG LESFRDLDPE QGHTVYAKKL WTAPELLRMA SPPVRGSQAG 
DVYSFGIILQ EIALRSGVFH VEGLDLSPKE IIERVTRGEQ PPFRPSLALQ SHLEELGLLM 
QRCWAEDPQE RPPFQQIRLT LRKFNRENSS NILDNLLSRM EQYANNLEEL VEERTQAYLE 
EKRKAEALLY QILPHSVAEQ LKRGETVQAE AFDSVTIYFS DIVGFTALSA ESTPMQVVTL 
LNDLYTCFDA VIDNFDVYKV ETIGDAYMVV SGLPVRNGRL HACEVARMAL ALLDAVRSFR 
IRHRPQEQLR LRIGIHTGPV CAGVVGLKMP RYCLFGDTVN TASRMESNGE ALKIHLSSET 
KAVLEEFGGF ELELRGDVEM KGKGKVRTYW LLGERGSSTR G