NPPA

Summary

NPPA (natriuretic peptide A, HGNC:7939) is a protein-coding gene on chromosome 1p36.22, encoding Natriuretic peptides A (P01160). Hormone that plays a key role in mediating cardio-renal homeostasis, and is involved in vascular remodeling and regulating energy metabolism.

The protein encoded by this gene belongs to the natriuretic peptide family. Natriuretic peptides are implicated in the control of extracellular fluid volume and electrolyte homeostasis. This protein is synthesized as a large precursor (containing a signal peptide), which is processed to release a peptide from the N-terminus with similarity to vasoactive peptide, cardiodilatin, and another peptide from the C-terminus with natriuretic-diuretic activity. Mutations in this gene have been associated with atrial fibrillation familial type 6. This gene is located adjacent to another member of the natriuretic family of peptides on chromosome 1.

Source: NCBI Gene 4878 — RefSeq curated summary.

At a glance

• Gene–disease (curated): atrial fibrillation, familial, 6 (Moderate, GenCC) — +4 more curated relationships
• GWAS associations: 39
• Clinical variants (ClinVar): 28 total — 1 pathogenic
• Phenotypes (HPO): 52
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006172

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7939
Approved symbol	NPPA
Name	natriuretic peptide A
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175206
Ensembl biotype	protein_coding
OMIM	108780
Entrez	4878

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000376476, ENST00000376480, ENST00000953330

RefSeq mRNA: 1 — MANE Select: NM_006172 NM_006172

CCDS: CCDS139

Canonical transcript exons

ENST00000376480 — 3 exons

Exon	Start	End
ENSE00001470668	11845709	11846014
ENSE00001470685	11847562	11847783
ENSE00003491504	11847113	11847439

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 99.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 28.2154 / max 34863.9163, expressed in 89 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10337	27.5929	80
10338	0.3050	11
10335	0.1454	15
10333	0.0571	3
10339	0.0253	9
10332	0.0246	3
10331	0.0205	4
10336	0.0152	1
10340	0.0132	6
10341	0.0108	6

Top tissues by expression

268 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	99.99	gold quality
cardiac atrium	UBERON:0002081	99.98	gold quality
right atrium auricular region	UBERON:0006631	99.98	gold quality
vena cava	UBERON:0004087	98.77	gold quality
apex of heart	UBERON:0002098	96.51	gold quality
myocardium	UBERON:0002349	96.50	gold quality
pancreatic ductal cell	CL:0002079	95.45	gold quality
heart left ventricle	UBERON:0002084	94.38	gold quality
cardiac ventricle	UBERON:0002082	94.19	gold quality
left ventricle myocardium	UBERON:0006566	93.55	gold quality
heart	UBERON:0000948	93.39	gold quality
heart right ventricle	UBERON:0002080	92.71	gold quality
parotid gland	UBERON:0001831	87.32	silver quality
triceps brachii	UBERON:0001509	86.27	silver quality
gluteal muscle	UBERON:0002000	86.26	silver quality
mucosa of stomach	UBERON:0001199	82.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.18	gold quality
right frontal lobe	UBERON:0002810	79.30	gold quality
adenohypophysis	UBERON:0002196	78.60	gold quality
buccal mucosa cell	CL:0002336	77.40	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.08	gold quality
omental fat pad	UBERON:0010414	76.96	gold quality
skin of abdomen	UBERON:0001416	76.95	gold quality
peritoneum	UBERON:0002358	76.93	gold quality
gastrocnemius	UBERON:0001388	76.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	76.50	gold quality
adipose tissue of abdominal region	UBERON:0007808	76.27	gold quality
right testis	UBERON:0004534	76.15	gold quality
cingulate cortex	UBERON:0003027	75.98	gold quality
biceps brachii	UBERON:0001507	75.92	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-109979	yes	618.16
E-ANND-3	no	1.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ANKRD1, AP1, ATF6, BMPR1A, CAMTA1, CEBPE, DLX3, DLX5, EDN1, EGR1, FOS, FOSL1, GATA4, GATA5, GATA6, HAND1, HAND2, HESX1, HEY2, HIF1A, HNF4A, HOPX, HOXB7, JARID2, JUN, JUNB, JUND, KAT5, KLF4, LEF1, MEF2A, MEF2C, MYOG, NFATC4, NFKB2, NFKB, NKX2-2, NKX2-5, NR2F2, NR2F6

miRNA regulators (miRDB)

24 targeting NPPA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-3907	96.76	65.04	662
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-576-3P	96.14	65.63	773

Literature-anchored findings (GeneRIF, showing 40)

• Processing of pro-atrial natriuretic peptide by corin in cardiac myocytes. (PMID:11884416)
• examination of hormones and diseases that upregulate its expression (review) (PMID:12102171)
• Induction of IkappaB: atrial natriuretic peptide as a regulator of the NF-kappaB pathway (PMID:12135603)
• expression of heart failure marker gene(ANF) are upregulated in the failing heart (PMID:12145475)
• intrapericardial ANP may reflect the peptide concentration in the myocardial interstitium and may represent a paracrine regulatory mechanism, which seems independent of ANP-induced putative antiischemic influences (PMID:12270761)
• plasma levels of adrenomedullin, ANP and brain natriuretic peptide (BNP)increased with aging; ANP and BNP increased in association with pulse pressure; possible relation between levels and age-related changes in cardiovascular system (PMID:12484513)
• results suggest that atrial natriuretic peptide can potentiate endothelial regeneration by cGMP-dependent protein kinase stimulation and subsequent Akt protein and extracellular signal-regulated kinase 1/2 activations (PMID:12505872)
• The ScaI ANP polymorphism may be associated with nonfatal myocardial infarction and the extent of CAD. (PMID:12514664)
• ANP may play a role in dendritic cell (DC)-mediated immune regulation: treatment of DCs with ANP plus lipopolysaccharide promotes differentiation of naive CD4+ T cells into a Th2 phenotype. (PMID:12794112)
• Pro-ANP plasma levels are independently and inversely related to anxiety. This might be part of a negative feedback loop limiting psychological distress and its adverse autonomic consequences in severe heart failure. (PMID:12883099)
• Plasma ANP concentrations were significantly higher in marathon runners than in controls and judo groups, and positively correlated with the left atrial dimension index, but negatively correlated with ejection fraction. (PMID:12890912)
• ANF mediates the inhibition of TNF-alpha-induced expression of MCP-1. (PMID:12960255)
• CRH administration induced sympathotonic effects which were antagonized by ANP (PMID:14698679)
• Atrial natriuretic peptide gene polymorphisms increase susceptibility for ischemic stroke. (PMID:15017020)
• In humans, in addition to catecholamines, ANP plays a noticeable role in the control of lipid mobilization. This pathway becomes of major importance when subjects are submitted to chronic treatment with a beta-blocker. (PMID:15033935)
• The 2238C allele of atrial natriuretic peptide may affect the course of nephropathy in inadequately controlled type 1 diabetic patients. (PMID:15111511)
• In hypertrophic cardiomyopathy, plasma BNP may reflect intraventricular pressure gradient and left ventricular diastolic dysfunction. Plasma ANP reflects left ventricular diastolic dysfunction. (PMID:15118286)
• Does not decrease ADH, aldosterone and corticosterone response to dehydration. Apparently modulates ADH, aldosterone and corticosterone responses to other stimuli in the dehydrated state. (PMID:15648549)
• Ligand- and retinoid X receptor-dependent, Vitamin D receptor-mediated suppression of human ANP gene promoter activity. (PMID:15837528)
• Polyhydramnios in fetuses with heart conditions might be explained by increased fetal diuresis secondary to increased ANP production (PMID:16113566)
• Plasma concentrations of ANF were higher in children with congenital heart defects with left ventricular volume overload compared with right ventricular volume overload or pressure overload. (PMID:16117728)
• Results suggest that atrial natriuretic factor is involved in the control of lipolysis during exercise and that it contributes to stimulation of lipolysis during repeated bouts of exercise. (PMID:16291573)
• The 664A allele of the Atrial Natriuretic Peptide(ANP) polymorphism is associated with lower levels of ApoA1 and HDL-C in Familial Hypercholesterolemia patients, but not with Coronary Artery Disease risk. (PMID:16721833)
• ANP/NPRA system significantly contributes to ventricular remodeling in human essential hypertension. (PMID:16875975)
• Both ANP and BNP expression were higher in heart failure than in control samples. (PMID:16962475)
• NPPA in patients with myocardial infarction may be a useful parameter to guide prescription of cardiac rehabilitation. (PMID:17292492)
• Nppa and Npr1 gene polymorphisms are not associated with normal-tension glaucoma, suggesting that this gene does not have an important role in the pathogenesis of optic neuropathy in this disease. (PMID:17460430)
• The ANP gene variant was associated with early blood pressure increase and predisposition to develop hypertension. (PMID:17525707)
• irculating ANF was strongly associated with glucose tolerance status in diabetic and nondiabetic patients in heart transplantation. (PMID:17580193)
• Tbx18 interacts with Gata4 and Nkx2-5 and competes Tbx5-mediated activation of the cardiac Natriuretic peptide precursor type a-promoter. Tbx18 down-regulates Tbx6-activated Delta-like 1 expression in the somitic mesoderm in vivo (PMID:17584735)
• the -A2843G polymorphism in the ANP gene promoter might be a genetic risk factor for the development of left ventricular hypertrophy in patients with hypertension (PMID:17672826)
• Atrial natriuretic hormone in the hypertensive subjects were lower in the Jordan Valley and lower in Irbid City than normotensives. (PMID:17693975)
• The ScaI polymorphism of the ANP gene might be an important additive genetic factor influencing neurohormonal activation and disease progression in severe HF. (PMID:17890443)
• ANP and corin are expressed at the mRNA level in human adipose tissue and preadipocytes (PMID:17890485)
• elevated ANP (atrial natriuretic peptide ) plasma levels are closely related to cardiac abnormalities in elderly subjects (PMID:17900714)
• Increased ANP in patients with idiopathic hypertension may indicate the coexistence of complications with types of left ventricular hypertrophy (LVH). High concentrations of BNP may specifically suggest concentric LVH. (PMID:17901852)
• human heart LIM promotes the specific expression of the ANF gene by co-operating with Nkx2.5 (PMID:17927564)
• Determined plasma NT-proANP levels in relation to severity of mitral valve regurgitation. (PMID:17943627)
• natriuretic peptide precursor A gene plays a significant role in blood pressure regulation and development of hypertension. (PMID:17984371)
• Increase in CD34-positive cells may be functionally correlated with the increase in ANP production in idiopathic dilated cardiomyopathies. (PMID:18092954)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nppa	ENSDARG00000052960
mus_musculus	Nppa	ENSMUSG00000041616
rattus_norvegicus	Nppa	ENSRNOG00000008176

Paralogs (1): NPPB (ENSG00000120937)

Protein

Protein identifiers

Natriuretic peptides A — P01160 (reviewed: P01160)

Alternative names: Atrial natriuretic factor prohormone, Atrial natriuretic peptide prohormone, Atriopeptigen, Cardiodilatin, preproCDD-ANF

All UniProt accessions (2): B0ZBE8, P01160

UniProt curated annotations — full annotation on UniProt →

Function. Hormone that plays a key role in mediating cardio-renal homeostasis, and is involved in vascular remodeling and regulating energy metabolism. Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins, such as PRKG1, that drive various biological responses. Regulates vasodilation, natriuresis, diuresis and aldosterone synthesis and is therefore essential for regulating blood pressure, controlling the extracellular fluid volume and maintaining the fluid-electrolyte balance. Also involved in inhibiting cardiac remodeling and cardiac hypertrophy by inducing cardiomyocyte apoptosis and attenuating the growth of cardiomyocytes and fibroblasts. Plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus, and thus prevents pregnancy-induced hypertension. In adipose tissue, acts in various cGMP- and PKG-dependent pathways to regulate lipid metabolism and energy homeostasis. This includes up-regulating lipid metabolism and mitochondrial oxygen utilization by activating the AMP-activated protein kinase (AMPK), and increasing energy expenditure by acting via MAPK11 to promote the UCP1-dependent thermogenesis of brown adipose tissue. Binds the clearance receptor NPR3 which removes the hormone from circulation. May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, vasodilation, and inhibiting aldosterone synthesis. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. However reports on the involvement of this peptide in mammal blood volume and blood pressure homeostasis are conflicting; according to a report, in vivo it is not sufficient to activate cGMP and does not inhibit collecting duct transport nor effect diuresis and natriuresis. Appears to bind to specific receptors that are distinct from the receptors bound by atrial natriuretic peptide and vessel dilator. Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption. May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, and vasodilation. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. However reports on the involvement of this peptide in mammal blood volume and blood pressure homeostasis are conflicting; according to a report it is not sufficient to activate cGMP and does not inhibit collecting duct transport nor effect diuresis and natriuresis. Appears to bind to specific receptors that are distinct from the receptors bound by the atrial natriuretic and long-acting natriuretic peptides. Possibly functions in protein excretion in urine by maintaining the integrity of the proximal tubules and enhancing protein excretion by decreasing proximal tubular protein reabsorption. May have a role in cardio-renal homeostasis through regulation of diuresis and inhibiting aldosterone synthesis. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. May have a role in potassium excretion but not sodium excretion (natriuresis). Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption. Hormone produced in the kidneys that appears to be important for maintaining cardio-renal homeostasis. Mediates vasodilation, natriuresis and diuresis primarily in the renal system, in order to maintain the extracellular fluid volume and control the fluid-electrolyte balance. Specifically binds and stimulates cGMP production by renal transmembrane receptors, likely NPR1. Urodilatin not ANP, may be the natriuretic peptide responsible for the regulation of sodium and water homeostasis in the kidney. May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis and in vitro, vasodilates renal artery strips. May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis and in vitro, vasodilates renal artery strips. May have a role in cardio-renal homeostasis through regulation of regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, vasodilates intestinal smooth muscle but not smooth muscle strips. May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, selectively vasodilates intestinal and vascular smooth muscle strips. May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, selectively vasodilates intestinal smooth muscle but not vascular smooth muscle strips.

Subunit / interactions. Homodimer; disulfide-linked antiparallel dimer.

Subcellular location. Secreted Secreted Secreted Secreted Secreted. Perikaryon. Cell projection Secreted.

Tissue specificity. Detected in the kidney distal tubular cells (at protein level). Present in urine (at protein level). Detected in atrial and ventricular plasma samples, and in adipocytes (at protein level). Detected in urine in one study. However, was not detected in urine in another study. In the brain, predominantly expressed in the gray matter with very weak expression in the white matter (at protein level). Localizes to astrocyte-like structures throughout the white matter, and in the cerebral vessels detected in the leptomeningeal and parenchymal vessels, and endothelium and smooth muscle layers (at protein level). Relatively low levels of expression in the kidneys compared to urodilatin (at protein level).

Post-translational modifications. The precursor molecule is proteolytically cleaved by CORIN at Arg-123 to produce atrial natriuretic peptide. Undergoes further proteolytic cleavage by unknown proteases to give rise to long-acting natriuretic peptide, vessel dilator and kaliuretic peptide. Additional processing gives rise to the auriculin and atriopeptin peptides. In the kidneys, alternative processing by an unknown protease results in the peptide urodilatin. Cleavage by MME initiates degradation of the factor and thereby regulates its activity. Degraded by IDE (in vitro). During IDE degradation, the resulting products can temporarily stimulate NPR2 to produce cGMP, before the fragments are completely degraded and inactivated by IDE (in vitro). Degraded by IDE. Phosphorylation on Ser-129 decreases vasorelaxant activity.

Disease relevance. Atrial standstill 2 (ATRST2) [MIM:615745] A rare arrhythmia characterized by the absence of electrical and mechanical activity in the atria. Electrocardiographically, it is characterized by bradycardia, the absence of P waves, and a junctional narrow complex escape rhythm. The disease is caused by variants affecting the gene represented in this entry. Atrial fibrillation, familial, 6 (ATFB6) [MIM:612201] A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the natriuretic peptide family.

RefSeq proteins (1): NP_006163* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000663	Natr_peptide	Family
IPR002407	Natriuretic_peptide_atrial	Family
IPR030480	Natr_peptide_CS	Conserved_site
IPR050787	Natriuretic_peptide	Family

Pfam: PF00212

UniProt features (32 total): peptide 12, mutagenesis site 4, sequence variant 3, strand 3, region of interest 2, site 2, signal peptide 1, chain 1, modified residue 1, disulfide bond 1, sequence conflict 1, propeptide 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
1YK0	X-RAY DIFFRACTION	2.4
7BRH	X-RAY DIFFRACTION	2.45
7BRJ	X-RAY DIFFRACTION	2.7
9DZF	ELECTRON MICROSCOPY	2.7
9DZJ	ELECTRON MICROSCOPY	2.7
7BRK	X-RAY DIFFRACTION	2.85
9RBD	ELECTRON MICROSCOPY	2.96
9DZH	ELECTRON MICROSCOPY	3
3N57	X-RAY DIFFRACTION	3.03
8TG9	ELECTRON MICROSCOPY	3.08
9BCQ	ELECTRON MICROSCOPY	3.1
9RBW	ELECTRON MICROSCOPY	3.3
1ANP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01160-F1	64.11	0.12

Antibody-complex structures (SAbDab): 1 — 8TG9

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 123–124 (cleavage; by corin); 130–131 (cleavage; by mme)

Post-translational modifications (1): 129

Disulfide bonds (1): 130–146

Mutagenesis-validated functional residues (4):

Position	Phenotype
123	loss of cleavage by corin.
124–129	no effect on degradation of atrial natriuretic peptide by ide.
124–126	reduced degradation of atrial natriuretic peptide by ide; when associated with n-147–151-y del.
147–151	reduced degradation of atrial natriuretic peptide by ide; when associated with s-124–126-r del.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-2032785	YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-5578768	Physiological factors
R-HSA-977225	Amyloid fiber formation
R-HSA-212436	Generic Transcription Pathway
R-HSA-392499	Metabolism of proteins
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 398 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, BIOCARTA_GCR_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_MAP_KINASE_ACTIVITY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, CAR_TNFRSF25, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_MUSCLE_STRETCH, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY

GO Biological Process (37): response to hypoxia (GO:0001666), negative regulation of systemic arterial blood pressure (GO:0003085), cardiac conduction system development (GO:0003161), aortic valve morphogenesis (GO:0003180), cGMP biosynthetic process (GO:0006182), protein folding (GO:0006457), receptor guanylyl cyclase signaling pathway (GO:0007168), neuropeptide signaling pathway (GO:0007218), female pregnancy (GO:0007565), regulation of blood pressure (GO:0008217), positive regulation of heart rate (GO:0010460), obsolete positive regulation of cGMP-mediated signaling (GO:0010753), cardiac muscle hypertrophy in response to stress (GO:0014898), obsolete cGMP-mediated signaling (GO:0019934), negative regulation of cell growth (GO:0030308), response to insulin (GO:0032868), response to muscle stretch (GO:0035994), sodium ion export across plasma membrane (GO:0036376), vasodilation (GO:0042311), negative regulation of JUN kinase activity (GO:0043508), regulation of atrial cardiac muscle cell membrane repolarization (GO:0060372), positive regulation of cardiac muscle contraction (GO:0060452), cell growth involved in cardiac muscle cell development (GO:0061049), cellular response to hydrogen peroxide (GO:0070301), cellular response to mechanical stimulus (GO:0071260), cellular response to glucose stimulus (GO:0071333), synaptic signaling via neuropeptide (GO:0099538), regulation of calcium ion transmembrane transport via high voltage-gated calcium channel (GO:1902514), positive regulation of potassium ion export across plasma membrane (GO:1903766), negative regulation of collecting lymphatic vessel constriction (GO:1903815), cellular response to angiotensin (GO:1904385), response to 3-methylcholanthrene (GO:1904681), system process (GO:0003008), signal transduction (GO:0007165), regulation of vascular permeability (GO:0043114), negative regulation of blood pressure (GO:0045776), blood vessel diameter maintenance (GO:0097746)

GO Molecular Function (7): signaling receptor binding (GO:0005102), hormone activity (GO:0005179), neuropeptide hormone activity (GO:0005184), hormone receptor binding (GO:0051427), neuropeptide receptor binding (GO:0071855), protein binding (GO:0005515), guanylate cyclase activator activity (GO:0030250)

GO Cellular Component (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), brush border (GO:0005903), protein-containing complex (GO:0032991), mast cell granule (GO:0042629), cell projection (GO:0042995), perikaryon (GO:0043204), perinuclear region of cytoplasm (GO:0048471), glycinergic synapse (GO:0098690)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Generic Transcription Pathway	1
Cardiac conduction	1
Metabolism of proteins	1
RNA Polymerase II Transcription	1
Muscle contraction	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
response to stress	1
response to decreased oxygen levels	1
regulation of systemic arterial blood pressure	1
negative regulation of blood pressure	1
cardiac muscle tissue development	1
aortic valve development	1
heart valve morphogenesis	1
purine ribonucleotide biosynthetic process	1
cyclic nucleotide biosynthetic process	1
cGMP metabolic process	1
cellular process	1
protein maturation	1
enzyme-linked receptor protein signaling pathway	1
G protein-coupled receptor signaling pathway	1
multi-organism reproductive process	1
multi-multicellular organism process	1
blood circulation	1
regulation of biological quality	1
regulation of heart rate	1
positive regulation of heart contraction	1
muscle hypertrophy in response to stress	1
cardiac muscle hypertrophy	1
cardiac muscle adaptation	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
response to peptide hormone	1
response to mechanical stimulus	1
sodium ion transmembrane transport	1
export across plasma membrane	1
blood vessel diameter maintenance	1
JUN kinase activity	1
negative regulation of MAP kinase activity	1
regulation of JUN kinase activity	1
negative regulation of JNK cascade	1
protein binding	1
receptor ligand activity	1
hormone activity	1

Protein interactions and networks

STRING

2593 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPPA	NPR3	P17342	999
NPPA	NPR1	P16066	999
NPPA	NPR2	P20594	995
NPPA	NPPC	P23582	984
NPPA	NPPB	P16860	969
NPPA	AGT	P01019	948
NPPA	REN	P00797	941
NPPA	NKX2-5	P52952	934
NPPA	GATA4	P43694	895
NPPA	CORIN	Q9Y5Q5	871
NPPA	ADM	P35318	858
NPPA	MYH6	P13533	838
NPPA	ACE	P12821	836
NPPA	MYH7	P12883	834
NPPA	TBX5	Q99593	828

IntAct

21 interactions, top by confidence:

A	B	Type	Score
MAGEA12	NPPA	psi-mi:“MI:0915”(physical association)	0.720
NPPA	MAGEA12	psi-mi:“MI:0915”(physical association)	0.720
NPPA	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	NPPA	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	NPPA	psi-mi:“MI:0915”(physical association)	0.560
NPPA	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
NPPA	VGF	psi-mi:“MI:0914”(association)	0.530
NPPA	HSF2BP	psi-mi:“MI:0915”(physical association)	0.000
NPPA	MAGEA12	psi-mi:“MI:0915”(physical association)	0.000
NPPA	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
NPPA	UBQLN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (87): NPPA (Two-hybrid), UBQLN1 (Two-hybrid), PM20D1 (Affinity Capture-MS), A2ML1 (Affinity Capture-MS), NUDT8 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), OBSCN (Affinity Capture-MS), GDPD3 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS), NDUFAF7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), NDUFAF5 (Affinity Capture-MS), ALOX15B (Affinity Capture-MS), PMPCA (Affinity Capture-MS), METAP1 (Affinity Capture-MS)

ESM2 similar proteins: B0VXV8, B8K1V9, D1MZV3, D5J9S0, D9IX97, O46540, O77559, P01021, P01142, P01143, P01160, P05125, P06296, P07499, P0C7P5, P0C7P6, P12272, P13085, P16860, P18104, P22858, P23582, P27596, P52211, P55206, P55207, P56283, P56469, P61312, P68515, P79799, P83228, P84715, P97297, Q09GK2, Q27J49, Q2PE51, Q2XXL8, Q61839, Q62949

Diamond homologs: O46540, O46541, P01160, P01161, P05125, P07499, P07500, P07501, P07634, P09196, P13204, P16859, P18144, P18908, P18909, P22642, P24259, P27104, P27596, P83962, P83964, Q805D7, Q805D8, Q805E9, Q9GLD0, Q9GLK4, B0VXV8, B3EWY2, B3EWY3, D1MZV3, P0CV87, P0DMD6, P13205, P16860, P18104, P23582, P40753, P55206, P55207, P56283

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
NPPA	up-regulates	NPR1	binding
ANKRD1	“down-regulates quantity by repression”	NPPA	“transcriptional regulation”
TBX5	“up-regulates quantity by expression”	NPPA	“transcriptional regulation”
CAMTA1	“up-regulates quantity by expression”	NPPA	“transcriptional regulation”
JARID2	“down-regulates quantity by repression”	NPPA	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

28 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	8
Likely benign	10
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
17788	NM_006172.4(NPPA):c.456_*1del (p.Ter152TrpextTer?)	Pathogenic

SpliceAI

169 predictions. Top by Δscore:

Variant	Effect	Δscore
1:11847442:T:C	acceptor_gain	1.0000
1:11846015:C:CC	acceptor_gain	0.9900
1:11847107:TCTTA:T	donor_loss	0.9900
1:11847109:TTA:T	donor_loss	0.9900
1:11847110:TA:T	donor_loss	0.9900
1:11847111:A:AC	donor_gain	0.9900
1:11847111:A:AT	donor_loss	0.9900
1:11847111:AC:A	donor_gain	0.9900
1:11847112:C:CC	donor_gain	0.9900
1:11847112:CC:C	donor_gain	0.9900
1:11847440:C:CC	acceptor_gain	0.9900
1:11847441:T:C	acceptor_gain	0.9900
1:11847442:T:TC	acceptor_gain	0.9900
1:11847106:CTCTT:C	donor_loss	0.9800
1:11847438:TT:T	acceptor_gain	0.9800
1:11847550:T:A	donor_gain	0.9800
1:11847556:CCCTA:C	donor_loss	0.9800
1:11847557:CCTA:C	donor_loss	0.9800
1:11847558:CTAC:C	donor_loss	0.9800
1:11847559:TACCT:T	donor_loss	0.9800
1:11847560:A:AG	donor_loss	0.9800
1:11847561:C:A	donor_loss	0.9800
1:11846012:GTA:G	acceptor_gain	0.9700
1:11846013:TA:T	acceptor_gain	0.9700
1:11847436:AATT:A	acceptor_gain	0.9700
1:11847437:ATT:A	acceptor_gain	0.9700
1:11847439:TC:T	acceptor_loss	0.9700
1:11847440:C:A	acceptor_loss	0.9700
1:11846010:CAGTA:C	acceptor_gain	0.9600
1:11846014:AC:A	acceptor_loss	0.9600

AlphaMissense

980 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:11847170:G:C	F131L	0.994
1:11847170:G:T	F131L	0.994
1:11847172:A:G	F131L	0.994
1:11847126:C:G	C146S	0.993
1:11847127:A:T	C146S	0.993
1:11847171:A:C	F131C	0.993
1:11847175:A:G	C130R	0.992
1:11847126:C:T	C146Y	0.989
1:11847127:A:G	C146R	0.989
1:11847174:C:T	C130Y	0.989
1:11847174:C:G	C130S	0.988
1:11847175:A:T	C130S	0.988
1:11847137:G:C	S142R	0.987
1:11847137:G:T	S142R	0.987
1:11847139:T:G	S142R	0.987
1:11847173:G:C	C130W	0.986
1:11847174:C:A	C130F	0.986
1:11847126:C:A	C146F	0.985
1:11847168:C:T	G132E	0.984
1:11847161:C:A	R134S	0.983
1:11847161:C:G	R134S	0.983
1:11847150:A:T	I138N	0.982
1:11847156:T:A	D136V	0.982
1:11847157:C:G	D136H	0.981
1:11847125:A:C	C146W	0.979
1:11847162:C:G	R134T	0.979
1:11847152:C:A	R137S	0.978
1:11847152:C:G	R137S	0.978
1:11847162:C:A	R134M	0.978
1:11847150:A:C	I138S	0.977

dbSNP variants (sampled 300 via entrez): RS1000287820 (1:11849287 T>A,C), RS1000613938 (1:11848301 C>T), RS1000643538 (1:11848560 A>G), RS1001728343 (1:11848593 C>T), RS1002898170 (1:11848261 G>A,C), RS1003357016 (1:11847930 G>A,T), RS1003632 (1:11849352 C>T), RS1003736245 (1:11846460 A>G), RS1004143376 (1:11847776 C>G,T), RS1004223776 (1:11849413 A>C), RS1004475971 (1:11848806 C>T), RS1004508860 (1:11849053 C>G), RS1005191711 (1:11847108 C>G), RS1005449974 (1:11846139 C>G,T), RS1005677533 (1:11848540 A>G)

Disease associations

OMIM: gene MIM:108780 | disease phenotypes: MIM:612201, MIM:615745

GenCC curated gene-disease

Disease	Classification	Inheritance
atrial fibrillation, familial, 6	Moderate	Autosomal dominant
atrial standstill	Supportive	Autosomal dominant
familial atrial fibrillation	Supportive	Autosomal dominant
atrial standstill 2	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dilated cardiomyopathy	No Known Disease Relationship	AR

Mondo (4): atrial fibrillation, familial, 6 (MONDO:0012816), atrial standstill 2 (MONDO:0014329), atrial standstill (MONDO:0015281), familial atrial fibrillation (MONDO:0018054)

Orphanet (1): Isolated atrial standstill (Orphanet:1344)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001260	Dysarthria
HP:0001279	Syncope
HP:0001297	Stroke
HP:0001371	Flexion contracture
HP:0001627	Abnormal heart morphology
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001658	Myocardial infarction
HP:0001662	Bradycardia
HP:0001692	Atrial arrhythmia
HP:0001712	Left ventricular hypertrophy
HP:0001727	Thromboembolic stroke
HP:0001907	Thromboembolism
HP:0001962	Palpitations
HP:0002018	Nausea
HP:0002094	Dyspnea
HP:0002140	Ischemic stroke
HP:0002301	Hemiplegia
HP:0002315	Headache
HP:0002321	Vertigo
HP:0002381	Aphasia
HP:0002617	Vascular dilatation
HP:0003202	Skeletal muscle atrophy
HP:0003238	Hyperpepsinogenemia I
HP:0003546	Exercise intolerance
HP:0003560	Muscular dystrophy
HP:0003596	Middle age onset
HP:0004756	Ventricular tachycardia

GWAS associations

39 associations (top):

Study	Trait	p-value
GCST000395_2	Systolic blood pressure	2.000000e-13
GCST000445_2	Atrial fibrillation	6.000000e-07
GCST004923_1	Tuberculosis	1.000000e-11
GCST005207_1	Midregional pro atrial natriuretic peptide levels	4.000000e-13
GCST005207_2	Midregional pro atrial natriuretic peptide levels	3.000000e-09
GCST006190_19	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	6.000000e-16
GCST006190_20	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-18
GCST006190_21	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	7.000000e-19
GCST006190_26	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-17
GCST006190_27	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-21
GCST006190_28	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-18
GCST006190_41	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	6.000000e-13
GCST006190_67	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-11
GCST006192_1	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	9.000000e-20
GCST006192_14	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-14
GCST006192_16	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-29
GCST006192_17	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-21
GCST006192_2	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-32
GCST006192_28	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-13
GCST006192_3	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-20
GCST006192_88	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	6.000000e-18
GCST006193_11	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	5.000000e-16
GCST006193_12	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-22
GCST006193_24	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-12
GCST006193_50	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	6.000000e-16
GCST006193_51	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-20
GCST006193_52	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	7.000000e-19
GCST006193_65	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-11
GCST006193_9	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-19
GCST006195_22	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-31

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0008468	midregional pro atrial natriuretic peptide measurement
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0005763	pulse pressure measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C567400	Atrial Fibrillation, Familial, 6 (supp.)
C563984	Atrial Standstill (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293193 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,529 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL42583	SAMPATRILAT	2	3,529

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs5065	Efficacy	3	amlodipine;chlorthalidone	Cardiovascular Disease;Coronary Disease;Stroke

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5063	NPPA, NPPA-AS1	3	1.75	1	bumetanide;furosemide;torasemide
rs5065	CLCN6, NPPA, NPPA-AS1	3	2.00	1	amlodipine;chlorthalidone

ChEMBL bioactivities

11 potent at pChembl≥5 of 11 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.82	IC50	1.5	nM	CHEMBL1778526
8.47	IC50	3.4	nM	SAMPATRILAT
7.60	IC50	25	nM	CHEMBL1778529
7.24	IC50	58	nM	CHEMBL1778536
7.12	IC50	75	nM	CHEMBL1778528
7.09	IC50	82	nM	CHEMBL1778530
6.89	IC50	130	nM	CHEMBL1778527
6.89	IC50	130	nM	CHEMBL1778531
6.71	IC50	195	nM	CHEMBL1778534
6.68	IC50	210	nM	CHEMBL1778533
6.57	IC50	270	nM	CHEMBL1778532

PubChem BioAssay actives

11 with measured affinity, of 15 total; 11 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[(2S)-1-[[(1S)-1-carboxy-2-(4-phenylphenyl)ethyl]amino]-5-methyl-1-oxohexan-2-yl]amino]-4-phenylbutanoic acid	598053: Inhibition of atrial natriuretic peptide	ic50	0.0015	uM
(2S)-2-[[[(2S)-6-amino-2-(methanesulfonamido)hexanoyl]amino]methyl]-3-[1-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]carbamoyl]cyclopentyl]propanoic acid	598053: Inhibition of atrial natriuretic peptide	ic50	0.0034	uM
(2S)-2-[[1-[[(1S)-1-carboxy-2-(4-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl]amino]pentanoic acid	598053: Inhibition of atrial natriuretic peptide	ic50	0.0250	uM
(2S)-2-[[1-[[(1S)-1-carboxy-2-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]carbamoyl]cyclopentyl]amino]-4-methoxybutanoic acid	598053: Inhibition of atrial natriuretic peptide	ic50	0.0580	uM
(2S)-2-[[1-[[(1S)-1-carboxy-2-[4-(2-methylpropyl)-1,3-oxazol-2-yl]ethyl]carbamoyl]cyclopentyl]amino]pentanoic acid	598053: Inhibition of atrial natriuretic peptide	ic50	0.0750	uM
(2S)-2-[[1-[[(1S)-1-carboxy-2-(5-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl]amino]pentanoic acid	598053: Inhibition of atrial natriuretic peptide	ic50	0.0820	uM
(2S)-2-[[1-[[(1S)-1-carboxy-2-(4-ethyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl]amino]pentanoic acid	598053: Inhibition of atrial natriuretic peptide	ic50	0.1300	uM
(2S)-2-[[1-[[(1S)-1-carboxy-2-(4-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl]amino]-4-methoxybutanoic acid	598053: Inhibition of atrial natriuretic peptide	ic50	0.1300	uM
(2S)-2-[[1-[[(1S)-1-carboxy-2-[5-(4-chlorophenyl)-1,3-oxazol-2-yl]ethyl]carbamoyl]cyclopentyl]amino]-4-methoxybutanoic acid	598053: Inhibition of atrial natriuretic peptide	ic50	0.1950	uM
(2S)-2-[[1-[[(1S)-1-carboxy-2-(4-methyl-5-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl]amino]-4-methoxybutanoic acid	598053: Inhibition of atrial natriuretic peptide	ic50	0.2100	uM
(2S)-2-[[1-[[(1S)-1-carboxy-2-(5-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl]amino]-4-methoxybutanoic acid	598053: Inhibition of atrial natriuretic peptide	ic50	0.2700	uM

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	increases expression	4
Hydrocortisone	increases expression, decreases secretion	3
Resveratrol	affects cotreatment, decreases expression	2
Aldosterone	decreases secretion	2
Spironolactone	decreases expression	2
Verapamil	affects cotreatment, affects secretion, increases expression	2
MYK-461	increases expression, decreases reaction	1
bisphenol F	increases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
bisphenol A	increases expression	1
manganese chloride	decreases expression	1
15-hydroxy-5,8,11,13-eicosatetraenoic acid	increases expression	1
dan-shen root extract	increases expression, decreases reaction	1
aflatoxin B2	decreases methylation	1
CHOP protocol	increases expression	1
BAEC protocol	affects expression	1
CGP 52608	affects binding, increases reaction	1
1,25-dihydroxyvitamin D	decreases expression	1
omapatrilat	increases expression	1
tricarbonyldichlororuthenium (II) dimer	decreases reaction, increases expression	1
jinfukang	increases expression	1
Carvedilol	decreases expression	1
Fulvestrant	decreases reaction, increases expression	1
Irbesartan	increases expression	1
Alprostadil	decreases expression	1
Angiotensin-Converting Enzyme Inhibitors	decreases expression	1
Atenolol	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cocaine	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1291041	Binding	Displacement of [125I]-ANF from atrial natriuretic factor receptor at 1 to 3 uM	Conformationally constrained NR2B selective NMDA receptor antagonists derived from ifenprodil: Synthesis and biological evaluation of tetrahydro-3-benzazepine-1,7-diols. — Bioorg Med Chem

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04075994	Not specified	COMPLETED	Atrial Fibrillation Health Literacy and Information Technology Trial
NCT04076020	Not specified	COMPLETED	Atrial Fibrillation Health Literacy and Information Technology Trial in Rural Pennsylvania Counties