NOS1

Summary

NOS1 (nitric oxide synthase 1, HGNC:7872) is a protein-coding gene on chromosome 12q24.22, encoding Nitric oxide synthase 1 (P29475). Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body.

The protein encoded by this gene belongs to the family of nitric oxide synthases, which synthesize nitric oxide from L-arginine. Nitric oxide is a reactive free radical, which acts as a biologic mediator in several processes, including neurotransmission, and antimicrobial and antitumoral activities. In the brain and peripheral nervous system, nitric oxide displays many properties of a neurotransmitter, and has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. This protein is ubiquitously expressed, with high level of expression in skeletal muscle. Multiple transcript variants that differ in the 5’ UTR have been described for this gene but the full-length nature of these transcripts is not known. Additionally, alternatively spliced transcript variants encoding different isoforms (some testis-specific) have been found for this gene.

Source: NCBI Gene 4842 — RefSeq curated summary.

At a glance

• Gene–disease (curated): idiopathic achalasia (Supportive, GenCC)
• Clinical variants (ClinVar): 258 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000620

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7872
Approved symbol	NOS1
Name	nitric oxide synthase 1
Location	12q24.22
Locus type	gene with protein product
Status	Approved
Aliases	nNOS
Ensembl gene	ENSG00000089250
Ensembl biotype	protein_coding
OMIM	163731
Entrez	4842

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000317775, ENST00000338101, ENST00000477584, ENST00000549189, ENST00000618760

RefSeq mRNA: 4 — MANE Select: NM_000620 NM_000620, NM_001204213, NM_001204214, NM_001204218

CCDS: CCDS41842, CCDS55890

Canonical transcript exons

ENST00000317775 — 29 exons

Exon	Start	End
ENSE00000835092	117311466	117311592
ENSE00000835093	117330345	117331489
ENSE00001358200	117361512	117361626
ENSE00001839331	117208142	117215324
ENSE00003714411	117253638	117253754
ENSE00003714713	117260465	117260609
ENSE00003714789	117222715	117222863
ENSE00003719994	117220075	117220269
ENSE00003721374	117263889	117263974
ENSE00003721564	117247348	117247522
ENSE00003721842	117280725	117280866
ENSE00003724744	117226683	117226770
ENSE00003727724	117225016	117225137
ENSE00003728985	117227431	117227641
ENSE00003732512	117268043	117268144
ENSE00003734603	117265316	117265510
ENSE00003737112	117234565	117234758
ENSE00003737876	117243297	117243435
ENSE00003739104	117231962	117232131
ENSE00003740930	117259026	117259130
ENSE00003741882	117242627	117242705
ENSE00003746038	117286104	117286266
ENSE00003746339	117218046	117218164
ENSE00003747561	117290298	117290426
ENSE00003747765	117277959	117278098
ENSE00003751599	117288074	117288219
ENSE00003751747	117272385	117272559
ENSE00003752983	117258397	117258455
ENSE00003753843	117285241	117285332

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 91.38.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0274 / max 124.5772, expressed in 184 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133504	0.2486	73
133505	0.1982	78
133502	0.1377	59
133503	0.1373	52
133500	0.1268	54
133501	0.0599	29
206918	0.0540	28
133499	0.0358	16
133506	0.0290	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of tongue	UBERON:0011876	91.38	gold quality
biceps brachii	UBERON:0001507	88.72	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.66	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.40	gold quality
pons	UBERON:0000988	83.20	gold quality
tongue	UBERON:0001723	82.31	gold quality
muscle of leg	UBERON:0001383	81.06	gold quality
gastrocnemius	UBERON:0001388	81.05	gold quality
skeletal muscle tissue	UBERON:0001134	80.59	gold quality
muscle organ	UBERON:0001630	80.29	gold quality
dorsal root ganglion	UBERON:0000044	80.09	gold quality
diaphragm	UBERON:0001103	77.77	gold quality
buccal mucosa cell	CL:0002336	76.90	gold quality
vastus lateralis	UBERON:0001379	76.85	gold quality
deltoid	UBERON:0001476	76.41	silver quality
muscle tissue	UBERON:0002385	76.24	gold quality
putamen	UBERON:0001874	76.00	gold quality
trigeminal ganglion	UBERON:0001675	75.91	gold quality
tibialis anterior	UBERON:0001385	75.88	silver quality
quadriceps femoris	UBERON:0001377	75.83	gold quality
lateral globus pallidus	UBERON:0002476	75.59	gold quality
superior vestibular nucleus	UBERON:0007227	75.20	gold quality
pancreatic ductal cell	CL:0002079	74.94	silver quality
ventral tegmental area	UBERON:0002691	74.68	gold quality
caudate nucleus	UBERON:0001873	74.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.81	gold quality
entorhinal cortex	UBERON:0002728	73.31	gold quality
superior surface of tongue	UBERON:0007371	72.48	gold quality
cerebellar vermis	UBERON:0004720	71.77	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, DLX4, EGR1, EP300, ESR1, FOS, GRHL3, HIF1A, NFKB1, NFKB, NFKBIA, NR0B1, NR5A1, NR5A2, NRF1, POU2F2, POU4F2, RELA, SP1, TAL1

miRNA regulators (miRDB)

321 targeting NOS1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4725-3P	99.96	69.53	2520

Literature-anchored findings (GeneRIF, showing 40)

• fine mapping and single nucleotide polymorphism association results of candidate genes for asthma and related phenotypes (PMID:11668616)
• An alternative promoter of the human neuronal nitric oxide synthase gene is expressed specifically in Leydig cells. (PMID:11786430)
• quantitative expression of nNOS first exon variants in different human tissues and the characterization of the basal nNOS exon 1c promoter (PMID:11960979)
• ligand and protein vibrations at the substrate binding site. A study by FTIR. (PMID:12081486)
• allelic association of the gene with schizophrenia (PMID:12140778)
• assembly and activation of the heme-deficient neuronal enzyme with various porphyrins (PMID:12237228)
• Data report a 89-nucleotide alternatively spliced exon in human neuronal nitric oxide synthase located in the 5’-untranslated region between exon 1 variants and a common exon 2 that contains the translational initiation codon. (PMID:12403769)
• Association analysis of five polymorphic microsatellite markers in cluster headache (CH) patients reveals that genetic variations in the NOS1 gene do not contribute greatly to CH susceptibility. (PMID:12421162)
• nitric oxide synthases(inducible, brain and endothelial) were expressed in human pregnant term uterus and did not change in the myometrium during labor (PMID:12445599)
• expression in neurons of the Nuc. suprachiasmaticus (SCN) of depressed patients and matched controls (PMID:12485841)
• calmodulin activates electron transfer in the flavin domain of human neuronal nitric oxide synthase (PMID:12646269)
• Nitric oxide participates in the phosphorylation of eIF2alpha since nNOS processes are closely related to eIF2alpha(P) positive cells in temporal lobe epilepsy with hippocampal sclerosis (PMID:12686399)
• rate of intramolecular electron transfer between the two flavins in the iNOS flavin domain was faster than that of the nNOS flavin domain. (PMID:12777376)
• NOS1 is strongly expressed in most tubules of the human nephron. Epithelial cells may be major source of nitric oxide in human kidney under physiologic conditions. (PMID:12787407)
• nNOS staining was found in nerve fibers branching within seminal vesicle tissue (PMID:12802542)
• Results describe the expression of nitric oxide synthases 1, 2, and 3 in patients with chronic obstructive pulmonary disease, suggesting their involvement in muscle dysfunction in this disease. (PMID:12816735)
• There is no obvious association between ecNOS polymorphism and preeclampsia. (PMID:12908999)
• Variations in the NOS1 gene may contribute to atopy without this relationship being reflected by FENO. (PMID:12911502)
• Nitric oxide liberated from enteric neurons participates in the chloride secretory response to stroking in human jejunum in vitro. (PMID:12947326)
• nNOS can differentially regulate the ERK signal transduction pathway in a manner dependent on the presence of l-arginine and the production of NO*. (PMID:14602725)
• The increased NO production with increased expression of iNOS and ncNOS may contribute to the pathological and physiological features of UVB-induced erythema and skin inflammation. (PMID:14615895)
• Association analysis for the CA repeat polymorphism of the neuronal nitric oxide synthase (NOS1) gene and schizophrenia. (PMID:14623375)
• Cu,Zn superoxide dismutase and nitric oxide synthase in neurodegenerative processes (review) (PMID:14711010)
• MPP(+)-dependent aconitase inactivation, Tf-iron uptake, and oxidant generation result in the depletion of intracellular tetrahydrobiopterin, leading to the uncoupling of nNOS activity (PMID:14752097)
• IFN-gamma regulates NOS-1 expression through posttranscriptional and posttranslational mechanisms. (PMID:14980078)
• nitric noxide release by nitric oxide synthase 1 (neuronal) would significantly affect available smooth muscle nitric oxide (PMID:15033959)
• human mast cell lines produce NO in both cytoplasmic and nuclear compartments, and endogenously produced NO can regulate leukotriene production. (PMID:15044250)
• The nNOS gene polymorphism may not confer increased susceptibility to Tardive Dyskinesia, although more investigations on other populations are warranted. (PMID:15075442)
• NOS1 gene may participate in pathogenesis of high total serum IgE levels in allergic diseases. NOS1 may be candidate gene for IgE-mediated allergy. (PMID:15080837)
• Neuronal NOS expression in the prefrontal cortex was significantly higher in individuals with schizophrenia. (PMID:15094474)
• Intron4 polymorphism of the nitric oxide synthase gene is associated with the development of lupus nephritis. (PMID:15119548)
• Intracellular factors able to induce abnormalities in the nNOS monomer/dimer equilibrium could lead to pancreatic beta-cell dysfunction. (PMID:15161750)
• In trained vastus lateralis, NOS 1 protein and immunostaining at myofibers II were significantly increased at the end of head-down-tilt bed rest. (PMID:15180967)
• nNOS expression is regulated in the process of cutaneous wound repair. (PMID:15191553)
• increased activity of nNOS may be involved in the neuroprotection conferred by 17beta-estradiol. (PMID:15194886)
• Constitutive NOS activities are responsible for E2-induced NO production in neuroblastoma cells. Differential activation of NOS isoforms in these cells occurs in response to different treatments. (PMID:15242984)
• neuronal nitric-oxide synthase activity through serine 741 phosphorylation is inhibited by Calcium/calmodulin-dependent protein kinase I (PMID:15251453)
• NOS-1 mRNA and protein levels hint that not only NOS-3, but also NOS-1 may be involved in the regulation of systemic hyperdynamic circulation and portal hypertension. (PMID:15287858)
• CHIP is an E3 ligase for nNOS whose action is facilitated by (and possibly requires) its interaction with nNOS-bound hsp70 (PMID:15466472)
• The T/T genotype of the neuronal nitric oxide synthase C276T SNP seems to be associated wtith Alzheimer’s disease in Italy population, particularly with early onset. (PMID:15765269)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nos1	ENSDARG00000068910
mus_musculus	Nos1	ENSMUSG00000029361
rattus_norvegicus	Nos1	ENSRNOG00000001130

Paralogs (5): NOS2 (ENSG00000007171), MTRR (ENSG00000124275), POR (ENSG00000127948), NOS3 (ENSG00000164867), NDOR1 (ENSG00000188566)

Protein

Protein identifiers

Nitric oxide synthase 1 — P29475 (reviewed: P29475)

Alternative names: Constitutive NOS, NC-NOS, NOS type I, Neuronal NOS, Nitric oxide synthase, brain, Peptidyl-cysteine S-nitrosylase NOS1

All UniProt accessions (2): P29475, B3VK56

UniProt curated annotations — full annotation on UniProt →

Function. Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.

Subunit / interactions. Homodimer. Interacts with DLG4; the interaction possibly being prevented by the association between NOS1 and CAPON. Forms a ternary complex with CAPON and RASD1. Forms a ternary complex with CAPON and SYN1. Interacts with ZDHHC23. Interacts with NOSIP; which may impair its synaptic location. Interacts with HTR4. Interacts with SLC6A4. Interacts with VAC14. Interacts (via N-terminal domain) with DLG4 (via N-terminal tandem pair of PDZ domains). Interacts with SLC6A4. Forms a complex with ASL, ASS1 and SLC7A1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway. Interacts with DMD; localizes NOS1 to sarcolemma in muscle cells. Interacts with DYNLL1; inhibits the nitric oxide synthase activity.

Subcellular location. Cell membrane. Sarcolemma. Cell projection. Dendritic spine.

Tissue specificity. Isoform 1 is ubiquitously expressed: detected in skeletal muscle and brain, also in testis, lung and kidney, and at low levels in heart, adrenal gland and retina. Not detected in the platelets. Isoform 3 is expressed only in testis. Isoform 4 is detected in testis, skeletal muscle, lung, and kidney, at low levels in the brain, but not in the heart and adrenal gland.

Post-translational modifications. Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and Hsp40 (in vitro).

Activity regulation. Stimulated by calcium/calmodulin. Inhibited by DYNLL1 that prevents the dimerization of the protein. Inhibited by NOSIP.

Cofactor. Binds 1 FAD. Binds 1 FMN. Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.

Domain organisation. The PDZ domain participates in protein-protein interaction, and is responsible for targeting nNos to synaptic membranes. Mediates interaction with VAC14.

Similarity. Belongs to the NOS family.

Isoforms (5)

UniProt ID	Names	Canonical?
P29475-1	1, N-NOS-1	yes
P29475-2	2, N-NOS-2
P29475-3	3, TN-NOS, TN-NOSB
P29475-4	4, TEX2-insertion
P29475-5	5, nNOSmu

RefSeq proteins (4): NP_000611, NP_001191142, NP_001191143, NP_001191147 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001094	Flavdoxin-like	Domain
IPR001433	OxRdtase_FAD/NAD-bd	Domain
IPR001478	PDZ	Domain
IPR001709	Flavoprot_Pyr_Nucl_cyt_Rdtase	Domain
IPR003097	CysJ-like_FAD-binding	Domain
IPR004030	NOS_N	Domain
IPR008254	Flavodoxin/NO_synth	Domain
IPR012144	NOS_euk	Family
IPR017927	FAD-bd_FR_type	Domain
IPR017938	Riboflavin_synthase-like_b-brl	Homologous_superfamily
IPR023173	NADPH_Cyt_P450_Rdtase_alpha	Homologous_superfamily
IPR029039	Flavoprotein-like_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR036119	NOS_N_sf	Homologous_superfamily
IPR039261	FNR_nucleotide-bd	Homologous_superfamily
IPR044940	NOS_dom_2	Homologous_superfamily
IPR044943	NOS_dom_1	Homologous_superfamily
IPR044944	NOS_dom_3	Homologous_superfamily
IPR050607	NOS	Family

Pfam: PF00175, PF00258, PF00595, PF00667, PF02898

Enzyme classification (BRENDA):

• EC 1.14.13.39 — nitric-oxide synthase (NADPH) (BRENDA: 31 organisms, 140 substrates, 179 inhibitors, 88 Km, 25 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-ARGININE	0.0019–68.5	28
NADPH	0.0003–0.0041	9
TETRAHYDROBIOPTERIN	—	6
ADRIAMYCIN	0.012–0.078	5
MENADIONE	0.01–0.041	5
MITOMYCIN C	0.0073–0.055	5
NGAMMA-HYDROXY-L-ARGININE	0.019–0.129	5
2’,3’-DIALDEHYDE-NADPH	0.0008	1
CALMODULIN	—	1
NITROBLUE TETRAZOLIUM	0.016	1
NITRIC OXIDE	—	0

Catalyzed reactions (Rhea), 1 shown:

• 2 L-arginine + 3 NADPH + 4 O2 + H(+) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H2O (RHEA:19897)

UniProt features (123 total): binding site 46, strand 24, helix 22, sequence conflict 6, region of interest 5, splice variant 5, sequence variant 5, domain 3, modified residue 3, turn 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

121 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8BI9	X-RAY DIFFRACTION	1.44
8BI8	X-RAY DIFFRACTION	1.59
6CID	X-RAY DIFFRACTION	1.75
6CIC	X-RAY DIFFRACTION	1.75
6PNG	X-RAY DIFFRACTION	1.77
6NG4	X-RAY DIFFRACTION	1.78
5VV0	X-RAY DIFFRACTION	1.8
6NGD	X-RAY DIFFRACTION	1.8
6NGI	X-RAY DIFFRACTION	1.8
7TS6	X-RAY DIFFRACTION	1.8
9CVS	X-RAY DIFFRACTION	1.8
9CVX	X-RAY DIFFRACTION	1.8
6PO9	X-RAY DIFFRACTION	1.81
6POA	X-RAY DIFFRACTION	1.81
6PO5	X-RAY DIFFRACTION	1.82
7US8	X-RAY DIFFRACTION	1.82
8FGF	X-RAY DIFFRACTION	1.83
7UAM	X-RAY DIFFRACTION	1.84
7TS5	X-RAY DIFFRACTION	1.84
6PNH	X-RAY DIFFRACTION	1.85
7TS4	X-RAY DIFFRACTION	1.85
8FGG	X-RAY DIFFRACTION	1.86
6AV4	X-RAY DIFFRACTION	1.87
9CVW	X-RAY DIFFRACTION	1.87
6PO8	X-RAY DIFFRACTION	1.9
5UO1	X-RAY DIFFRACTION	1.9
6AV5	X-RAY DIFFRACTION	1.9
6NG8	X-RAY DIFFRACTION	1.9
6NGB	X-RAY DIFFRACTION	1.9
7TS7	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29475-F1	80.12	0.52

Functional residue map

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

Ligand- & substrate-binding residues (46): 339; 420 (axial binding residue); 483; 592; 593; 597; 682; 683; 696; 711; 766; 767 …

Post-translational modifications (3): 852, 862, 863

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1222556	ROS and RNS production in phagocytes
R-HSA-392154	Nitric oxide stimulates guanylate cyclase
R-HSA-5578775	Ion homeostasis

MSigDB gene sets: 0 (showing top):

GO Biological Process (43): response to hypoxia (GO:0001666), regulation of sodium ion transport (GO:0002028), L-arginine catabolic process (GO:0006527), nitric oxide biosynthetic process (GO:0006809), potassium ion transport (GO:0006813), calcium ion transport (GO:0006816), striated muscle contraction (GO:0006941), obsolete nitric oxide mediated signal transduction (GO:0007263), myoblast fusion (GO:0007520), response to heat (GO:0009408), response to hormone (GO:0009725), negative regulation of calcium ion transport into cytosol (GO:0010523), regulation of cardiac muscle contraction by calcium ion signaling (GO:0010882), response to lipopolysaccharide (GO:0032496), multicellular organismal response to stress (GO:0033555), xenobiotic catabolic process (GO:0042178), vasodilation (GO:0042311), negative regulation of potassium ion transport (GO:0043267), positive regulation of neuron apoptotic process (GO:0043525), cell redox homeostasis (GO:0045454), negative regulation of blood pressure (GO:0045776), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of neurogenesis (GO:0050767), negative regulation of serotonin uptake (GO:0051612), establishment of localization in cell (GO:0051649), negative regulation of calcium ion transport (GO:0051926), regulation of cardiac muscle contraction (GO:0055117), regulation of postsynaptic membrane potential (GO:0060078), cellular response to growth factor stimulus (GO:0071363), positive regulation of the force of heart contraction (GO:0098735), synaptic signaling by nitric oxide (GO:0099163), positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0106071), positive regulation of sodium ion transmembrane transport (GO:1902307), regulation of calcium ion transmembrane transport via high voltage-gated calcium channel (GO:1902514), positive regulation of membrane repolarization during ventricular cardiac muscle cell action potential (GO:1905026), cell communication (GO:0007154), blood circulation (GO:0008015), regulation of metal ion transport (GO:0010959), signaling (GO:0023052)

GO Molecular Function (18): nitric-oxide synthase activity (GO:0004517), calcium channel regulator activity (GO:0005246), calmodulin binding (GO:0005516), FMN binding (GO:0010181), sodium channel regulator activity (GO:0017080), heme binding (GO:0020037), tetrahydrobiopterin binding (GO:0034617), arginine binding (GO:0034618), peptidyl-cysteine S-nitrosylase activity (GO:0035605), transmembrane transporter binding (GO:0044325), cadmium ion binding (GO:0046870), calcium-dependent protein binding (GO:0048306), flavin adenine dinucleotide binding (GO:0050660), NADP binding (GO:0050661), scaffold protein binding (GO:0097110), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (25): photoreceptor inner segment (GO:0001917), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), caveola (GO:0005901), postsynaptic density (GO:0014069), sarcoplasmic reticulum (GO:0016529), Z disc (GO:0030018), T-tubule (GO:0030315), protein-containing complex (GO:0032991), sarcoplasmic reticulum membrane (GO:0033017), sarcolemma (GO:0042383), dendritic spine (GO:0043197), calyx of Held (GO:0044305), membrane raft (GO:0045121), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), cell periphery (GO:0071944), endomembrane system (GO:0012505), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Innate Immune System	1
Platelet homeostasis	1
Cardiac conduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	4
response to stress	3
metal ion transport	2
ion channel regulator activity	2
anion binding	2
binding	2
cation binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
response to decreased oxygen levels	1
sodium ion transport	1
regulation of metal ion transport	1
arginine metabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
biosynthetic process	1
nitric oxide metabolic process	1
muscle contraction	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
response to temperature stimulus	1
response to endogenous stimulus	1
response to chemical	1
regulation of calcium ion transport into cytosol	1
negative regulation of cytosolic calcium ion concentration	1
calcium ion transport into cytosol	1
negative regulation of calcium ion transmembrane transport	1
calcium-mediated signaling	1
regulation of cardiac muscle contraction	1
cardiac muscle contraction	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
multicellular organismal process	1
xenobiotic metabolic process	1
catabolic process	1
blood vessel diameter maintenance	1
potassium ion transport	1
regulation of potassium ion transport	1

Protein interactions and networks

STRING

2480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOS1	CALML6	Q8TD86	995
NOS1	CALML3	P27482	995
NOS1	CALML5	Q9NZT1	995
NOS1	CALML4	Q96GE6	995
NOS1	CALM1	P02593	994
NOS1	NOS1AP	O75052	994
NOS1	DLG4	P78352	993
NOS1	XDH	P47989	924
NOS1	DMD	P11532	895
NOS1	RASD1	Q9Y272	877
NOS1	GRIN2B	Q13224	836
NOS1	CAV3	P56539	809
NOS1	DAG1	Q14118	782
NOS1	SNTA1	Q13424	779
NOS1	CHAT	P28329	757

IntAct

293 interactions, top by confidence:

A	B	Type	Score
CUL9	TP53	psi-mi:“MI:0914”(association)	0.920
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
CSNK2B	NMT2	psi-mi:“MI:0914”(association)	0.660
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
NOS1	GRIN2A	psi-mi:“MI:0915”(physical association)	0.610
GRIN2A	NOS1	psi-mi:“MI:0407”(direct interaction)	0.610
E6	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
GJD4	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
FZD7	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
SLCO1C1	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
MMP24	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
RSRC2	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC15A5	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
PLEKHH2	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKZ	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN18	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
ORF putative E6	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
EPHA7	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN9	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN14	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP2	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
BPIFA2	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
SAPCD1	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
NOS1	CRHR1	psi-mi:“MI:0407”(direct interaction)	0.440
NOS1	EPHB3	psi-mi:“MI:0407”(direct interaction)	0.440
FZD10	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
NOS1	DGKI	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (62): PRKD1 (Affinity Capture-Western), NOS1 (Two-hybrid), NOS1 (Reconstituted Complex), NOS1 (Biochemical Activity), Ctbp1 (Affinity Capture-MS), NOS1 (Affinity Capture-Western), NOS1 (Reconstituted Complex), NOS1 (Two-hybrid), SOX2 (Reconstituted Complex), SOX2 (Affinity Capture-Western), NOS1 (Affinity Capture-Western), CKAP4 (Proximity Label-MS), NOS1 (Affinity Capture-Western), NOS1 (Reconstituted Complex), NOS1 (Affinity Capture-Western)

ESM2 similar proteins: A2WXR5, A2XTW9, A2Y0Q2, A2Y4R8, B8ADZ3, B8AMA8, B8B8C5, B8B8I3, B8BJV8, F1QGC8, I6LJ77, O19132, O81488, P05858, P0CR85, P11468, P29475, P29476, P49408, P58270, Q0P4G8, Q27571, Q29498, Q2R837, Q2T9V8, Q40359, Q5BL73, Q5XEM9, Q5ZK14, Q60DW3, Q6NRW0, Q6YTY3, Q6Z7F4, Q75IR6, Q7F2Z1, Q7T2A3, Q7XUW3, Q84TV4, Q8BGT8, Q8H383

Diamond homologs: A0A0A2J1Z6, A0A0C3HJL3, A0A0G4P2K0, A0A100IM63, A0A101MN42, A0A1B4XBH1, A0A1L9WUV2, A0A397HSG2, A0A3G9HRC2, A0A3Q9FEJ4, A0A3S9NM20, A0A411KZZ4, A0A455R5H4, A0A8K1AW54, A1DN29, A2QLV1, A2Y8E0, A7VMU4, B1B557, B2RML6, B8MV61, B8NHD9, B8NWW3, B8QHP5, C8V0D4, D4AY62, D7PI20, E9FCP5, F1SY49, F1SY74, F1SY83, G0KYB2, G5EJN7, G7XMT1, G9MLG2, I7ZK32, L8AXV5, M2YJD1, O00061, O08336

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
SNTA1	up-regulates	NOS1	relocalization
NOS1	“up-regulates quantity”	“nitric oxide”	“chemical modification”
NOS1	“form complex”	DGC	binding
DLG4	“up-regulates activity”	NOS1	binding
PRKD1	“up-regulates activity”	NOS1	phosphorylation
NOS1	“down-regulates activity”	HDAC2	s-nitrosylation
PRKCA	unknown	NOS1
PRKACA	unknown	NOS1	phosphorylation
CAMK1	“down-regulates activity”	NOS1	phosphorylation
CAMK2A	“down-regulates activity”	NOS1	phosphorylation
CAMK4	“down-regulates activity”	NOS1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 196 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Tight junction interactions	8	20.8×	2e-06
Assembly and cell surface presentation of NMDA receptors	6	10.7×	4e-03
Gap junction assembly	5	10.3×	8e-03
Neurexins and neuroligins	7	9.7×	3e-03
Neurotransmitter receptors and postsynaptic signal transmission	9	6.3×	3e-03
Transmission across Chemical Synapses	9	4.8×	8e-03
Signaling by GPCR	13	3.7×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
calcium-independent cell-cell adhesion	7	30.9×	2e-06
glutamate receptor signaling pathway	5	25.7×	2e-04
positive regulation of synaptic transmission, glutamatergic	7	24.0×	9e-06
monoatomic cation transmembrane transport	5	17.1×	1e-03
positive regulation of excitatory postsynaptic potential	5	14.5×	2e-03
maintenance of blood-brain barrier	5	13.2×	3e-03
bicellular tight junction assembly	7	12.7×	2e-04
excitatory postsynaptic potential	5	12.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	164
Likely benign	49
Benign	23

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

9451 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:117218135:A:C	F1400L	1.000
12:117218135:A:T	F1400L	1.000
12:117218137:A:G	F1400L	1.000
12:117218142:T:A	D1398V	1.000
12:117218142:T:G	D1398A	1.000
12:117218143:C:G	D1398H	1.000
12:117227498:G:C	S1183R	1.000
12:117227498:G:T	S1183R	1.000
12:117227500:T:G	S1183R	1.000
12:117234689:G:C	H1037Q	1.000
12:117234689:G:T	H1037Q	1.000
12:117243354:A:G	W969R	1.000
12:117243354:A:T	W969R	1.000
12:117247368:A:G	W935R	1.000
12:117247368:A:T	W935R	1.000
12:117247502:C:T	G890D	1.000
12:117247503:C:G	G890R	1.000
12:117259031:C:A	G823W	1.000
12:117259039:G:T	P820H	1.000
12:117259048:C:A	G817V	1.000
12:117259048:C:T	G817E	1.000
12:117259056:A:C	F814L	1.000
12:117259056:A:T	F814L	1.000
12:117259058:A:G	F814L	1.000
12:117259058:A:T	F814I	1.000
12:117259062:G:C	S812R	1.000
12:117259062:G:T	S812R	1.000
12:117259063:C:A	S812I	1.000
12:117259064:T:G	S812R	1.000
12:117259069:A:T	V810D	1.000

dbSNP variants (sampled 300 via entrez): RS1000006523 (12:117313158 C>T), RS1000013967 (12:117292081 T>C), RS1000086313 (12:117362140 G>A,T), RS1000101754 (12:117225199 A>G), RS1000106720 (12:117306909 C>T), RS1000112956 (12:117320146 A>G), RS1000113648 (12:117266534 T>C), RS1000116749 (12:117306618 C>T), RS1000122263 (12:117282161 A>T), RS1000135656 (12:117226523 T>C), RS1000165421 (12:117319811 G>A), RS1000171392 (12:117316531 A>G), RS1000177344 (12:117231167 A>C,G), RS1000200293 (12:117272310 G>A), RS1000222658 (12:117356690 C>A)

Disease associations

OMIM: gene MIM:163731 | disease phenotypes: MIM:179010

GenCC curated gene-disease

Disease	Classification	Inheritance
idiopathic achalasia	Supportive	Autosomal recessive

Mondo (2): pyloric stenosis, infantile hypertrophic, 1 (MONDO:0008355), idiopathic achalasia (MONDO:0019635)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2096621 (SELECTIVITY GROUP), CHEMBL2111405 (SELECTIVITY GROUP), CHEMBL3568 (SINGLE PROTEIN), CHEMBL4630725 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 71,984 (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
CHEMBL1201774	SAPROPTERIN	4	2,511
CHEMBL1371	CHLORZOXAZONE	4	16,752
CHEMBL256147	TILARGININE	3	2,020
CHEMBL114551	GW-274150	2	1,052
CHEMBL1911882	KD7040	2	8
CHEMBL225304	PIMAGEDINE	2	24,450
CHEMBL344760	AMINOTHIAZOLE	2	19,924
CHEMBL503356	PRAXADINE	2	1,712
CHEMBL7890	L-NAME	2	1,152
CHEMBL227744	NITROARGININE	1	2,403

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs149212925	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs77241831	NOS1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Nitric oxide synthases

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
compound 14j [PMID: 27050842]	Inhibition	7.89	pKi
L-NNA	Inhibition	7.82	pKi
Nωpropyl-L-arginine	Inhibition	7.2	pKi
3-bromo-7NI	Inhibition	6.5	pIC50
tilarginine	Inhibition	6.08	pKi
7NI	Inhibition	5.3	pIC50
GW274150	Inhibition	4.74	pIC50

Binding affinities (BindingDB)

106 measured of 158 human assays (180 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-[[(2R,4S)-4-[(6-amino-4-methyl-2-pyridinyl)methoxy]pyrrolidin-2-yl]methoxymethyl]-4-methylpyridin-2-amine	KI	10 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
N’-[4-[3-(dimethylamino)propyl]-2,3-dihydro-1,4-benzothiazin-7-yl]thiophene-2-carboximidamide	IC50	14 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
N1-((3R,4S)-4-((6-aminopyridin-2-yl)methyl)pyrrolidin-3-yl)-N2-(4-fluorobenzyl)ethane-1,2-diamine tetrahydrochloride	KI	17.7 nM	US-9090589: Specific nNOS inhibitors for the therapy and prevention of human melanoma
7-[[5-(methylaminomethyl)-3-pyridinyl]oxymethyl]quinolin-2-amine	KI	19 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
7-[[3-[(dimethylamino)methyl]phenoxy]methyl]quinolin-2-amine	KI	21 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
7-(pyridin-3-yloxymethyl)quinolin-2-amine	KI	21 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
4-Methyl-6-propyl-pyridin-2-ylamine	IC50	23 nM
6-[2-[5-[(2R)-1-amino-3-(6-amino-4-methyl-2-pyridinyl)propan-2-yl]-3-pyridinyl]ethyl]-4-methylpyridin-2-amine	KI	24 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
N1-{(+/-)-4’-[(6’’-amino-4’’-methylpyridin-2’’-yl)methyl]pyrrolidin-3’-yl}-N2-phenethylethane-1,2-diamine tetrahydrochloride	KI	24 nM	US-9090589: Specific nNOS inhibitors for the therapy and prevention of human melanoma
6-[[(2S,4R)-4-[(6-amino-4-methyl-2-pyridinyl)methoxy]pyrrolidin-2-yl]methoxymethyl]-4-methylpyridin-2-amine	KI	26 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
N’-[4-[3-(methylamino)propyl]-2,3-dihydro-1,4-benzothiazin-7-yl]thiophene-2-carboximidamide	IC50	28 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
6-[2-[5-[1-amino-3-(6-amino-4-methyl-2-pyridinyl)propan-2-yl]-3-pyridinyl]ethyl]-4-methylpyridin-2-amine	KI	30 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
7-[[3-(dimethylamino)phenoxy]methyl]quinolin-2-amine	KI	31 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
6-[[(2S,4S)-4-[(6-amino-4-methyl-2-pyridinyl)methoxy]pyrrolidin-2-yl]methoxymethyl]-4-methylpyridin-2-amine	KI	31 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
6-[[(2R)-3-amino-2-[(6-amino-4-methyl-2-pyridinyl)methoxy]propoxy]methyl]-4-methylpyridin-2-amine	KI	32 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
N’-[4-[2-(2-hydroxyethylamino)ethyl]-2,3-dihydro-1,4-benzothiazin-7-yl]thiophene-2-carboximidamide	IC50	34 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
6-[[(2R,4R)-4-[(6-amino-4-methyl-2-pyridinyl)methoxy]pyrrolidin-2-yl]methoxymethyl]-4-methylpyridin-2-amine	KI	34 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
7-[[3-[2-(methylamino)ethyl]phenoxy]methyl]quinolin-2-amine	KI	36 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
6-[[(2S,3S)-2-amino-3-[(6-amino-4-methyl-2-pyridinyl)methoxy]butoxy]methyl]-4-methylpyridin-2-amine	KI	37 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
NOS Inhibitor, 3h	KI	38 nM
6-[[3-[[2-(3-fluorophenyl)ethylamino]methyl]phenoxy]methyl]-4-methylpyridin-2-amine	KI	40 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
7-[[5-[(1S)-1-(methylamino)ethyl]-3-pyridinyl]oxymethyl]quinolin-2-amine	KI	46 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
6-[[(2R,3R)-2-amino-3-[(6-amino-4-methyl-2-pyridinyl)methoxy]butoxy]methyl]-4-methylpyridin-2-amine	KI	47 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
N’-[4-[2-(ethylamino)ethyl]-2,3-dihydro-1,4-benzothiazin-6-yl]thiophene-2-carboximidamide	IC50	50 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
7-[[3-(methylaminomethyl)anilino]methyl]quinolin-2-amine	KI	51 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
7-[[3-[2-(dimethylamino)ethoxy]phenoxy]methyl]quinolin-2-amine	KI	52 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
6-[2-[3-[1-amino-3-(6-amino-4-methyl-2-pyridinyl)propan-2-yl]phenyl]ethyl]-4-methylpyridin-2-amine	KI	53 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
7-[[4-chloro-3-(methylaminomethyl)phenoxy]methyl]quinolin-2-amine	KI	54 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
3-[2-(6-amino-4-methyl-2-pyridinyl)ethyl]-5-[methyl-[2-(methylamino)ethyl]amino]benzonitrile	KI	55 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
7-[[4-fluoro-3-(methylaminomethyl)phenoxy]methyl]quinolin-2-amine	KI	56 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
N’-[3-[2-(6-amino-4-methyl-2-pyridinyl)ethyl]phenyl]-N’-methylethane-1,2-diamine	KI	56 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
N’-[4-[2-(methylamino)ethyl]-2,3-dihydro-1,4-benzothiazin-7-yl]thiophene-2-carboximidamide	IC50	60 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
6-[[3-(3-aminopropoxy)phenoxy]methyl]-4-methylpyridin-2-amine	KI	60 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
7-[[5-[(1R)-1-(methylamino)ethyl]-3-pyridinyl]oxymethyl]quinolin-2-amine	KI	65 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
2-(6-amino-4-methyl-2-pyridinyl)-1-[3-[2-(6-amino-4-methyl-2-pyridinyl)ethyl]phenyl]ethanol	KI	70 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
6-[2-[5-[(2S)-1-amino-3-(6-amino-4-methyl-2-pyridinyl)propan-2-yl]-3-pyridinyl]ethyl]-4-methylpyridin-2-amine	KI	70 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
6-[2-[[(2S,4R)-4-[(6-amino-4-methyl-2-pyridinyl)methoxy]pyrrolidin-2-yl]methoxy]ethoxymethyl]-4-methylpyridin-2-amine	KI	70 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
7-[[5-[1-(methylamino)ethyl]-3-pyridinyl]oxymethyl]quinolin-2-amine	KI	74 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
7-[[3-[(dimethylamino)methyl]anilino]methyl]quinolin-2-amine	KI	78 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
N’-[4-[2-(methylamino)ethyl]-2,3-dihydro-1,4-benzoxazin-6-yl]thiophene-2-carboximidamide	IC50	80 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
N’-[4-[2-(methylamino)ethyl]-2,3-dihydro-1,4-benzothiazin-6-yl]thiophene-2-carboximidamide	IC50	80 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
6,6’-[(5-aminobenzene-1,3-diyl)diethane-2,1-diyl]bis(4-methylpyridin-2-amine)	KI	85 nM
N1-{(+/-)-4’-[(6’’-amino-4’’-methylpyridin-2’’-yl)methyl]pyrrolidin-3’-yl}ethane-1,2-diamine tetrahydrochloride	KI	98 nM	US-9090589: Specific nNOS inhibitors for the therapy and prevention of human melanoma
6,6’-(pyridine-2,6-diyldiethane-2,1-diyl)bis(4-methylpyridin-2-amine)	KI	99 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
N’-[3-[2-(6-amino-4-methyl-2-pyridinyl)ethyl]-5-fluorophenyl]-N,N’-dimethylethane-1,2-diamine	KI	105 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
N’-[3-[2-(6-amino-4-methyl-2-pyridinyl)ethyl]phenyl]-N’-methylpropane-1,3-diamine	KI	109 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
N’-(4-piperidin-4-yl-2,3-dihydro-1,4-benzothiazin-6-yl)thiophene-2-carboximidamide	IC50	110 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
N-[3-[2-(6-amino-4-methyl-2-pyridinyl)ethyl]phenyl]-N’,N’-dimethylethane-1,2-diamine	KI	111 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
4-methyl-6-[[3-(piperidin-4-ylmethoxy)phenoxy]methyl]pyridin-2-amine	KI	117 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
N’-[4-[2-(dimethylamino)ethyl]-2,3-dihydro-1,4-benzothiazin-7-yl]thiophene-2-carboximidamide	IC50	120 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity

ChEMBL bioactivities

1127 potent at pChembl≥5 of 1372 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.07	Ki	0.085	nM	CHEMBL474637
9.82	Ki	0.15	nM	CHEMBL227937
9.60	Ki	0.25	nM	CHEMBL526688
9.52	Ki	0.3	nM	CHEMBL44833
9.41	Ki	0.388	nM	CHEMBL510760
9.00	Kd	1	nM	CHEMBL106871
9.00	IC50	1	nM	CHEMBL106871
8.28	Ki	5.3	nM	CHEMBL594682
8.22	Ki	6	nM	CHEMBL96680
8.20	Ki	6.3	nM	CHEMBL96680
8.20	Ki	6.3	nM	CHEMBL552825
8.06	Ki	8.7	nM	CHEMBL262040
8.06	Ki	8.7	nM	CHEMBL555715
8.03	Ki	9.4	nM	CHEMBL475797
8.00	Ki	10	nM	CHEMBL3109188
8.00	IC50	10	nM	CHEMBL302657
7.96	Ki	11	nM	CHEMBL455310
7.96	Ki	11	nM	CHEMBL476988
7.96	Ki	11	nM	CHEMBL555794
7.96	Ki	11	nM	CHEMBL555584
7.92	IC50	12	nM	CHEMBL1944717
7.89	Ki	13	nM	CHEMBL3818373
7.85	Ki	14	nM	CHEMBL594682
7.85	IC50	14	nM	CHEMBL3675250
7.82	Ki	15	nM	NITROARGININE
7.80	IC50	16	nM	CHEMBL6808
7.80	Ki	16	nM	CHEMBL444422
7.75	Ki	17.7	nM	CHEMBL1233715
7.72	Ki	19	nM	CHEMBL5420690
7.72	Ki	19	nM	CHEMBL3736598
7.70	Ki	20	nM	CHEMBL4068062
7.70	IC50	20	nM	CHEMBL3216307
7.68	IC50	21	nM	CHEMBL191242
7.68	Ki	21	nM	CHEMBL4089246
7.68	Ki	21	nM	CHEMBL4532683
7.68	Ki	21	nM	CHEMBL5191295
7.68	Ki	21	nM	CHEMBL3736585
7.68	Ki	21	nM	CHEMBL3736588
7.64	Ki	23	nM	CHEMBL4590333
7.64	IC50	23	nM	CHEMBL302657
7.62	Ki	24	nM	CHEMBL1187747
7.62	Ki	24	nM	CHEMBL3262026
7.60	Ki	25	nM	CHEMBL3736587
7.60	Ki	25	nM	CHEMBL1615288
7.58	Ki	26	nM	CHEMBL3109186
7.55	IC50	28	nM	CHEMBL3639741
7.54	Ki	29	nM	CHEMBL4440481
7.54	Ki	29	nM	ETHYLISOTHIOUREA
7.54	Ki	29	nM	CHEMBL5189279
7.54	Ki	29	nM	CHEMBL483092

PubChem BioAssay actives

947 with measured affinity, of 1700 total; 50 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
N’-[(3S,4S)-4-[(6-amino-4-methyl-2-pyridinyl)methyl]pyrrolidin-3-yl]-N-[(4-chlorophenyl)methyl]ethane-1,2-diamine	414629: Inhibition of nNOS	ki	0.0001	uM
2-[(4S)-4-amino-5-(2-aminoethylamino)pentyl]-1-nitroguanidine	414629: Inhibition of nNOS	ki	0.0001	uM
(2S,4R)-4-[[(2S)-2-amino-5-[[amino(nitramido)methylidene]amino]pentanoyl]amino]pyrrolidine-2-carboxamide	414629: Inhibition of nNOS	ki	0.0001	uM
N’-[(3R,4S)-4-[(6-amino-4-methyl-2-pyridinyl)methyl]pyrrolidin-3-yl]-N-[(3-chlorophenyl)methyl]ethane-1,2-diamine	414629: Inhibition of nNOS	ki	0.0003	uM
(2S)-2-amino-5-[[amino(nitramido)methylidene]amino]-N-[(2S)-1,4-diamino-1-oxobutan-2-yl]pentanamide	414629: Inhibition of nNOS	ki	0.0003	uM
N’-[(3S,4S)-4-[(6-amino-2-pyridinyl)methyl]pyrrolidin-3-yl]ethane-1,2-diamine	414629: Inhibition of nNOS	ki	0.0004	uM
(2S)-2-amino-5-[[amino(ethylsulfanyl)methylidene]amino]pentanoic acid	2007148: Inhibition of human nNOS assessed as dissociation constant	kd	0.0010	uM
N’-[(3R,4R)-4-[(6-amino-4-methyl-2-pyridinyl)methyl]pyrrolidin-3-yl]-N-[2-(3-fluorophenyl)ethyl]ethane-1,2-diamine	593172: Inhibition of nNOS	ki	0.0053	uM
N’-[3-(aminomethyl)phenyl]furan-2-carboximidamide	2007182: Inhibition of human nNOS assessed as reduction of L-[14C]arginine to L-[14C]-citrulline conversion	ki	0.0060	uM
N’-[3-(aminomethyl)phenyl]furan-2-carboximidamide;dihydrobromide	146133: Inhibitory activity against human neuronal nitric oxide synthase (nNOS) isoenzyme.	ki	0.0063	uM
N’-[3-(aminomethyl)phenyl]thiophene-2-carboximidamide	404423: Inhibition of nNOS assessed as conversion of L-[3H]arginine to L-[3H]citrulline	ki	0.0087	uM
N’-[3-(aminomethyl)phenyl]thiophene-2-carboximidamide;dihydrobromide	146133: Inhibitory activity against human neuronal nitric oxide synthase (nNOS) isoenzyme.	ki	0.0087	uM
3-[[(3S,4S)-4-[(6-amino-2-pyridinyl)methyl]pyrrolidin-3-yl]amino]propan-1-ol	414629: Inhibition of nNOS	ki	0.0094	uM
4-methyl-6-propylpyridin-2-amine	146120: In vitro inhibition of human neuronal nitric oxide synthase.	ic50	0.0100	uM
N’-[3-(aminomethyl)phenyl]-2-fluoroethanimidamide	404423: Inhibition of nNOS assessed as conversion of L-[3H]arginine to L-[3H]citrulline	ki	0.0110	uM
N’-[3-(aminomethyl)phenyl]-2-fluoroethanimidamide;dihydrobromide	146133: Inhibitory activity against human neuronal nitric oxide synthase (nNOS) isoenzyme.	ki	0.0110	uM
N’-[3-(aminomethyl)phenyl]-2-methylsulfanylethanimidamide	404423: Inhibition of nNOS assessed as conversion of L-[3H]arginine to L-[3H]citrulline	ki	0.0110	uM
N’-[3-(aminomethyl)phenyl]-2-methylsulfanylethanimidamide;dihydrobromide	146133: Inhibitory activity against human neuronal nitric oxide synthase (nNOS) isoenzyme.	ki	0.0110	uM
4-[(3-chloro-N-pyrazin-2-ylanilino)methyl]-7,8-difluoro-1H-quinolin-2-one	643399: Inhibition of human nNOS expressed in HEK293 cells assessed as NO production by 2,3-diaminonapthalene-based fluorescence assay	ic50	0.0120	uM
4-methyl-6-[2-[5-[3-(methylamino)propyl]-3-pyridinyl]ethyl]pyridin-2-amine	1308021: Inhibition of human recombinant nNOS expressed in Escherichia coli using L-arginine as substrate assessed as reduction in NO production measured for 6 mins in presence of tetrahydrobiopterin by hemoglobin capture assay	ki	0.0130	uM
(2S)-2-amino-5-[[amino(nitramido)methylidene]amino]pentanoic acid	146133: Inhibitory activity against human neuronal nitric oxide synthase (nNOS) isoenzyme.	ki	0.0150	uM
2-[4-(2-carbamimidoylsulfanylethyl)phenyl]ethyl carbamimidothioate	404423: Inhibition of nNOS assessed as conversion of L-[3H]arginine to L-[3H]citrulline	ki	0.0160	uM
4-methyl-2,3,4,5-tetrahydropyridin-6-amine	241314: Inhibitory activity against human Neuronal nitric oxide synthase (nNOS)	ic50	0.0160	uM
6-[2-[5-[2-(dimethylamino)ethyl]-2,3-difluorophenyl]ethyl]-4-methylpyridin-2-amine;dihydrochloride	1982703: Inhibition of human nNOS expressed in Escherichia coli using human oxyhemoglobin by hemoglobin (Hb) NO capture assay	ki	0.0190	uM
4-[2-[(2-aminoquinolin-7-yl)methylamino]ethyl]-2-methylbenzonitrile	1458728: Inhibition of recombinant human nNOS expressed in Escherichia coli using L-arginine as substrate after 30 secs by hemoglobin capture assay	ki	0.0200	uM
N’-[1-[2-[(2S)-1-methylpyrrolidin-2-yl]ethyl]indol-5-yl]thiophene-2-carboximidamide;dihydrochloride	617462: Inhibition of human recombinant nNOS expressed in Sf9 cells assessed as conversion of [3H]-L-arginine to [3H]-L-citrulline by radiometric method	ic50	0.0200	uM
(4R,4aR,7aR)-4-methyl-4,4a,5,6,7,7a-hexahydro-3H-cyclopenta[b]pyridin-2-amine	241314: Inhibitory activity against human Neuronal nitric oxide synthase (nNOS)	ic50	0.0210	uM
4-[2-[(2-aminoquinolin-7-yl)methylamino]ethyl]-2-chlorobenzonitrile	1458728: Inhibition of recombinant human nNOS expressed in Escherichia coli using L-arginine as substrate after 30 secs by hemoglobin capture assay	ki	0.0210	uM
6-[2-[2,3-difluoro-5-[2-[(2S)-1-methylpyrrolidin-2-yl]ethyl]phenyl]ethyl]-4-methylpyridin-2-amine	1602916: Inhibition of human neuronal NOS expressed in Escherichia coli using L-arginine as substrate in presence of human oxyhemoglobin after 6 mins by hemoglobin NO capture assay	ki	0.0210	uM
4-methyl-6-[3-(methylamino)propyl]pyridin-2-amine	1862037: Inhibition of human nNOS using L-arginine as substrate assessed as reduction in NO production in the presence of NADPH by NO-hemoglobin capture assay	ki	0.0210	uM
6-[2-[2,3-difluoro-5-[2-[(2S)-1-methylazetidin-2-yl]ethyl]phenyl]ethyl]-4-methylpyridin-2-amine	1602916: Inhibition of human neuronal NOS expressed in Escherichia coli using L-arginine as substrate in presence of human oxyhemoglobin after 6 mins by hemoglobin NO capture assay	ki	0.0230	uM
6-[2-[5-[2-(6-amino-4-methyl-2-pyridinyl)ethyl]-3-pyridinyl]ethyl]-4-methylpyridin-2-amine	1799843: Inhibitory Assay from Article 10.1021/bi1013479: “Role of zinc in isoform-selective inhibitor binding to neuronal nitric oxide synthase .”	ki	0.0250	uM
propyl carbamimidothioate	2007165: Inhibition of nNOS in human DLD-1 cells assessed as reduction of L-[14C]arginine to L-[14C]citrulline conversion	ki	0.0290	uM
6-[2-[5-[3-(dimethylamino)propyl]-2,3-difluorophenyl]ethyl]-4-methylpyridin-2-amine	1602916: Inhibition of human neuronal NOS expressed in Escherichia coli using L-arginine as substrate in presence of human oxyhemoglobin after 6 mins by hemoglobin NO capture assay	ki	0.0290	uM
6-[3-(dimethylamino)propyl]-4-methylpyridin-2-amine	1862037: Inhibition of human nNOS using L-arginine as substrate assessed as reduction in NO production in the presence of NADPH by NO-hemoglobin capture assay	ki	0.0290	uM
ethyl carbamimidothioate	404423: Inhibition of nNOS assessed as conversion of L-[3H]arginine to L-[3H]citrulline	ki	0.0290	uM
4-[2-[(2-amino-4-methylquinolin-7-yl)methylamino]ethyl]-2-methylbenzonitrile	1458728: Inhibition of recombinant human nNOS expressed in Escherichia coli using L-arginine as substrate after 30 secs by hemoglobin capture assay	ki	0.0300	uM
6-[2-[3-[3-(dimethylamino)propyl]-5-fluorophenyl]ethyl]-4-methylpyridin-2-amine	1476978: Inhibition of human neuronal NOS expressed in Escherichia coli using L-arginine as substrate assessed as reduction in NO production by measuring oxidation of oxyHb to metHb measured for 6 mins by hemoglobin- NO capture assay	ki	0.0300	uM
N’-[2-[2-(1-methylpyrrolidin-2-yl)ethylamino]-1,3-benzothiazol-5-yl]thiophene-2-carboximidamide	294488: Inhibition of human neuronal NOS activity	ic50	0.0300	uM
3-[(2-amino-4-methylquinolin-7-yl)methoxy]-5-(methylaminomethyl)benzonitrile	1482931: Inhibition of recombinant human full-length nNOS expressed in Escherichia coli BL21(DE3) assessed as reduction in nitric oxide production using L-arginine as substrate measured for 5 mins in presence of calmodulin/10 uM H4B by hemoglobin capture assay	ki	0.0310	uM
7-[3-(aminomethyl)-4-(1,3-thiazol-4-ylmethoxy)phenyl]-4-methylquinolin-2-amine	1548626: Inhibition of human nNOS expressed in Escherichia coli expression system assessed as reduction in NO production in presence of L-arginine measured for 30 sec by hemoglobin capture assay	ki	0.0310	uM
4-[2-[(2-aminoquinolin-7-yl)methylamino]ethyl]benzonitrile	1458728: Inhibition of recombinant human nNOS expressed in Escherichia coli using L-arginine as substrate after 30 secs by hemoglobin capture assay	ki	0.0320	uM
4-methyl-7-[[3-(methylaminomethyl)phenoxy]methyl]quinolin-2-amine	1482931: Inhibition of recombinant human full-length nNOS expressed in Escherichia coli BL21(DE3) assessed as reduction in nitric oxide production using L-arginine as substrate measured for 5 mins in presence of calmodulin/10 uM H4B by hemoglobin capture assay	ki	0.0330	uM
N’-[4-[2-[(3-chlorophenyl)methylamino]ethyl]phenyl]thiophene-2-carboximidamide	225704: Inhibitory concentration against recombinant human (neuronal nitric oxide synthase) n-NOS	ic50	0.0350	uM
N’-[4-[2-[2-(3-chlorophenyl)ethylamino]ethyl]phenyl]thiophene-2-carboximidamide	730389: Inhibition of human nNOS	ic50	0.0350	uM
(4S,4aS,7aS)-4-methyl-4,4a,5,6,7,7a-hexahydro-3H-cyclopenta[b]pyridin-2-amine	241314: Inhibitory activity against human Neuronal nitric oxide synthase (nNOS)	ic50	0.0360	uM
3-[(2-aminoquinolin-7-yl)methoxy]-5-(methylaminomethyl)benzonitrile;dihydrochloride	1482931: Inhibition of recombinant human full-length nNOS expressed in Escherichia coli BL21(DE3) assessed as reduction in nitric oxide production using L-arginine as substrate measured for 5 mins in presence of calmodulin/10 uM H4B by hemoglobin capture assay	ki	0.0360	uM
6-[2-[3-[3-(dimethylamino)propyl]-2,6-difluorophenyl]ethyl]-4-methylpyridin-2-amine	1602916: Inhibition of human neuronal NOS expressed in Escherichia coli using L-arginine as substrate in presence of human oxyhemoglobin after 6 mins by hemoglobin NO capture assay	ki	0.0360	uM
6-[2-[5-[3-(dimethylamino)propyl]-3-pyridinyl]ethyl]-4-methylpyridin-2-amine	1308021: Inhibition of human recombinant nNOS expressed in Escherichia coli using L-arginine as substrate assessed as reduction in NO production measured for 6 mins in presence of tetrahydrobiopterin by hemoglobin capture assay	ki	0.0370	uM
2-[3-(2-carbamimidoylsulfanylethyl)phenyl]ethyl carbamimidothioate	2007165: Inhibition of nNOS in human DLD-1 cells assessed as reduction of L-[14C]arginine to L-[14C]citrulline conversion	ki	0.0370	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	4
bisphenol A	affects cotreatment, increases methylation, increases expression	3
entinostat	increases expression, affects cotreatment	2
Pesticides	affects response to substance, decreases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression	2
beta-N-methylamino-L-alanine	increases expression	1
apocarotenal	increases expression	1
propionaldehyde	increases expression	1
palytoxin	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
cypermethrin	decreases expression	1
5,5-dimethyl-1-pyrroline-1-oxide	affects cotreatment, increases oxidation	1
sodium sulfite	affects cotreatment, increases oxidation	1
aflatoxin B2	decreases methylation	1
lead chloride	decreases expression	1
N-(4-O-glycerol-3-methoxybenzyl)nonivamide	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
goniothalamin	decreases expression	1
7,8-diacetoxy-4-methylcoumarin	increases acetylation, increases reaction	1
2-palmitoylglycerol	increases expression	1
rofecoxib	affects expression	1
KMUP 1	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment, increases expression	1
3-(4-dimethylaminobenzylidene)-1,3-dihydroindol-2-one	affects binding	1
Bortezomib	decreases reaction, increases expression	1
Resveratrol	increases expression, affects reaction	1
Fulvestrant	affects cotreatment, increases methylation	1

ChEMBL screening assays

238 unique, capped per target: 234 binding, 2 functional, 1 unclassified, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003684	Binding	Selectivity ratio, EC50 for human iNOS over EC50 for human nNOS	Discovery of inducible nitric oxide synthase (iNOS) inhibitor development candidate KD7332, part 1: Identification of a novel, potent, and selective series of quinolinone iNOS dimerization inhibitors that are orally active in rodent pain models. — J Med Chem
CHEMBL4346022	Unclassified	Selectivity index, ratio of Ki for human iNOS expressed in Escherichia coli expression system to Ki for human nNOS expressed in Escherichia coli expression system	First Contact: 7-Phenyl-2-Aminoquinolines, Potent and Selective Neuronal Nitric Oxide Synthase Inhibitors That Target an Isoform-Specific Aspartate. — J Med Chem
CHEMBL4810222	ADMET	Inhibition of NOS (unknown origin) at 0.1 to 1 uM	Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1XS	Abcam A-549 NOS1 KO	Cancer cell line	Male
CVCL_D2C2	Abcam HCT 116 NOS1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01560559	PHASE3	COMPLETED	Peroral Endoscopic Myotomy for Primary Esophageal Achalasia
NCT03784365	PHASE3	UNKNOWN	Single-Versus Multiple-dose Antimicrobial Prophylaxis for Peroral Endoscopic Myotomy in Achalasia
NCT06189859	PHASE3	RECRUITING	Electrosurgical Modes for Endoscopic Submucosal Dissection in Peroral Endoscopic Esophageal Myotomy
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02025790	Not specified	UNKNOWN	POEM Versus Pneumatic Dilatation in Achalasia Cardia
NCT03186248	Not specified	COMPLETED	Randomized Clinical Trial Comparing Short Versus Long Oesophageal Myotomy in POEM for Achalasia Cardia.
NCT03438838	Not specified	UNKNOWN	Randomised Trial Between LHM Alone Vs LHM With Anterior Fundoplication In Achalasia Cardia
NCT04951739	Not specified	COMPLETED	To Investigate the Incidence of Reflux in Patients After Per-oral Endoscopic Myotomy in Achalasia Cardia Patients
NCT05729971	Not specified	COMPLETED	Nasogastric Tube After Laparoscopic Heller-Dor Myotomy
NCT06290882	Not specified	ACTIVE_NOT_RECRUITING	Endoscopic Versus Robotic Myotomy for Treatment of Achalasia
NCT07022886	Not specified	ACTIVE_NOT_RECRUITING	INCIDENCE, PREVALENCE AND OVERALL RISK OF ESOPHAGEAL CANCER IN ACHALASIA: A PROPENSITY-MATCHED POPULATION-BASED STUDY FROM A LARGE MULTICENTER DATABASE
NCT07167355	Not specified	NOT_YET_RECRUITING	Comparison of Balloon Dilatation and Per Oral Endoscopic Myotomy in Children With Achalasia Cardia
NCT07177222	Not specified	COMPLETED	Compare the Quality of Life of Patients With Achalasia Cardia (AC) After Laparoscopic and Open Esophagocardiomyotomy.
NCT07399652	Not specified	RECRUITING	Artificial Intelligence-Guided Detection of Blood Vessels to Enhance Safety in Third-Space Endoscopic Procedures
NCT07451301	Not specified	COMPLETED	Serum Anti-enteric Neuronal Antibodies in Patients With Achalasia and Their Association With Clinical Profiles