NNMT

Summary

NNMT (nicotinamide N-methyltransferase, HGNC:7861) is a protein-coding gene on chromosome 11q23.2, encoding Nicotinamide N-methyltransferase (P40261). Catalyzes the N-methylation of nicotinamide using the universal methyl donor S-adenosyl-L-methionine to form N1-methylnicotinamide and S-adenosyl-L-homocysteine, a predominant nicotinamide/vitamin B3 clearance pathway.

N-methylation is one method by which drug and other xenobiotic compounds are metabolized by the liver. This gene encodes the protein responsible for this enzymatic activity which uses S-adenosyl methionine as the methyl donor.

Source: NCBI Gene 4837 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 53 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006169

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7861
Approved symbol	NNMT
Name	nicotinamide N-methyltransferase
Location	11q23.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166741
Ensembl biotype	protein_coding
OMIM	600008
Entrez	4837

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 20 protein_coding, 5 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000299964, ENST00000535185, ENST00000535401, ENST00000541090, ENST00000541754, ENST00000542647, ENST00000545255, ENST00000546313, ENST00000713573, ENST00000858477, ENST00000858478, ENST00000858479, ENST00000858480, ENST00000858481, ENST00000858482, ENST00000858483, ENST00000858484, ENST00000858485, ENST00000858486, ENST00000858487, ENST00000858488, ENST00000858489, ENST00000947446, ENST00000947447, ENST00000947448, ENST00000947449

RefSeq mRNA: 4 — MANE Select: NM_006169 NM_001372045, NM_001372046, NM_001372047, NM_006169

CCDS: CCDS8368

Canonical transcript exons

ENST00000299964 — 3 exons

Exon	Start	End
ENSE00003676191	114297951	114298158
ENSE00004020355	114312045	114313536
ENSE00004020356	114296399	114296710

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 99.5865 / max 3768.5267, expressed in 1230 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116795	54.3978	1168
116797	22.4188	941
116798	17.4842	1002
116796	1.7628	567
116794	1.3613	613
116790	0.8008	160
116788	0.4720	127
116793	0.3374	164
116791	0.2252	111
116802	0.1726	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.91	gold quality
pericardium	UBERON:0002407	99.75	gold quality
tendon	UBERON:0000043	99.64	gold quality
vena cava	UBERON:0004087	99.59	gold quality
descending thoracic aorta	UBERON:0002345	99.58	gold quality
right lobe of liver	UBERON:0001114	99.55	gold quality
calcaneal tendon	UBERON:0003701	99.55	gold quality
ascending aorta	UBERON:0001496	99.53	gold quality
thoracic aorta	UBERON:0001515	99.53	gold quality
peritoneum	UBERON:0002358	99.52	gold quality
omental fat pad	UBERON:0010414	99.52	gold quality
popliteal artery	UBERON:0002250	99.50	gold quality
tibial artery	UBERON:0007610	99.50	gold quality
aorta	UBERON:0000947	99.49	gold quality
artery	UBERON:0001637	99.48	gold quality
mucosa of stomach	UBERON:0001199	99.47	gold quality
left coronary artery	UBERON:0001626	99.43	gold quality
coronary artery	UBERON:0001621	99.41	gold quality
synovial joint	UBERON:0002217	99.40	gold quality
saphenous vein	UBERON:0007318	99.38	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.38	gold quality
decidua	UBERON:0002450	99.36	gold quality
right coronary artery	UBERON:0001625	99.25	gold quality
left uterine tube	UBERON:0001303	99.23	gold quality
layer of synovial tissue	UBERON:0007616	99.22	gold quality
gall bladder	UBERON:0002110	99.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.93	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.92	gold quality
right lung	UBERON:0002167	98.88	gold quality
nerve	UBERON:0001021	98.77	gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-MTAB-8322	yes	2344.18
E-MTAB-6701	yes	2153.46
E-GEOD-130473	yes	2060.32
E-CURD-114	yes	1700.10
E-MTAB-10855	yes	1533.06
E-MTAB-9841	yes	1493.63
E-HCAD-13	yes	848.07
E-MTAB-6653	yes	794.75
E-MTAB-10662	yes	627.64
E-MTAB-8205	yes	493.95
E-MTAB-8142	yes	126.15
E-HCAD-1	yes	100.10
E-MTAB-10287	yes	66.99
E-HCAD-9	yes	61.29
E-MTAB-8410	yes	60.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1B, STAT3

Literature-anchored findings (GeneRIF, showing 40)

• A potential role in predicting response to radiation in bladder cancer (PMID:12216074)
• HNF-1beta functions as a transcription activator for NNMT gene expression in some papillary thyroid cancer cells (PMID:15486044)
• A genomewide exploration suggested NNMT as a new candidate and major determinant of plasma homocystein levels. (PMID:15849667)
• NNMT serum levels may have significance in the early detection and in the management of patients with colorectal cancer. (PMID:16166432)
• depsipeptide represses NNMT and HNF-1beta gene expression in some papillary thyroid cancer cells (PMID:16676400)
• NNMT genotype is not a strong determinant of the tHcy concentration but it may have a modifying effect on plasma homocysteine concentration in Japanese men (PMID:17434578)
• NNMT is a novel Stat3-regulated gene and may be a potential candidate for a tumor marker of various kinds of cancers (PMID:17922140)
• No association was found between infant nicotinamide N-methyl transferase gene variants and risk for spina bifida in our study population. (PMID:18553462)
• analysis identified genes known to be associated with cell invasion such as versican, and novel ones, including metallothionein 1E (MT1E) and nicotinamide N-methyltransferase (NNMT) (PMID:18724390)
• Adipose tissue ss a source of nicotinamide N-methyltransferase and homocysteine (PMID:18996527)
• For the first time, we associate the RFC1 80G>A and NNMT IVS -151C>T variants to an increased acute lymphoblastic leukemia susceptibility. (PMID:19020309)
• NNMT gene expression is associated with tumor stage and DFS time in hepatocellular carcinoma cases. (PMID:19216803)
• serum levels of NNMT were significantly higher in lung cancer patients than in COPD patients and healthy donors (PMID:19242722)
• the present study suggests that NNMT may have potential as a biomarker and as a therapeutic target for OSCCoral squamous cell carcinoma (PMID:19924637)
• NNMT is over-expressed in a large proportion in renal cell cancers. High NNMT expression is significantly associated with unfavorable prognosis. (PMID:20104648)
• NNMT has a crucial role in cellular invasion via activating PI3K/Akt/SP1/MMP-2 pathway in clear cell renal cell carcinoma (ccRCC). (PMID:21045016)
• This study suggested that NNMT is involved in the aetiology of schizophrenia (PMID:21791160)
• Structural basis of substrate recognition in human nicotinamide N-methyltransferase (PMID:21823666)
• a marked increase in enzyme activity in oral cancer (PMID:22628313)
• The nicotinamide N-methyltransferase expression levels were significantly higher in patients with bladder tumor compared to controls that showed very low or undetectable amounts of NNMT transcript and protein. (PMID:23097023)
• using metabolomics, observation that NNMT impairs the methylation potential of cancer cells by consuming methyl units from S-adenosyl methionine to create the stable metabolic product 1-methylnicotinamide (PMID:23455543)
• High serum NNMT is associated with kidney cancer. (PMID:23479363)
• NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways. (PMID:23764850)
• Data indicate that nicotinamide N-methyltransferase (NNMT) positively correlated with protein kinase B (pAkt) expression and was independent adverse prognosticators of patient survival. (PMID:23838801)
• The rs694539 variant of NNMT gene is a genetic risk factor for developing nonalcoholic steatohepatitis. (PMID:23964925)
• Genetic association of the rs694539 variant of nicotinamide-N-methyltransferase gene with bipolar disorder. (PMID:24004542)
• Down-regulation of NNMT induces apoptosis via the mitochondria-mediated pathway in breast cancer cells. (PMID:24558488)
• NNMT is associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis. (PMID:25115443)
• NNMT enhances the capacity of tumorigenesis associated with the inhibition of cell apoptosis and the promotion of cell cycle progression in human colorectal cancer cells (PMID:25201588)
• The downregulation of NNMT significantly reduced in vitro tumorigenicity of A549 cells. (PMID:25204218)
• results suggest that the NNMT SNP rs694539 may have a role in the etiology of schizophrenia in a Han Chinese female population (PMID:25317069)
• There were no associations between MTHFR C677T, NNMT rs694539 AG/AA polymorphisms and conotruncal heart disease. (PMID:25547204)
• Data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress. (PMID:25592232)
• White adipose tissue NNMT expression is regulated in human insulin resistance and type 2 diabetes and that plasma MNA correlates with increased tissue NNMT expression and the degree of insulin resistance. (PMID:25596852)
• increasing Nnmt expression or MNAM levels stabilizes sirtuin 1 protein, an effect that is required for their metabolic benefits (PMID:26168293)
• This finding, for the first time, suggests the involvement of the NNMT gene rs694539 variant in the etiology of epilepsy. (PMID:26215836)
• results further reinforce a central role for NNMT in the regulation of energy homeostasis and provide further mechanistic insight into the consequences of enhanced NNMT expression (PMID:26456643)
• Data show that nicotinamide N-methyltransferase (NNMT) and the metabolic state regulate pluripotency in embryonic stem cells (hESCs). (PMID:26571212)
• High expression level of NNMT is associated with pancreatic cancer. (PMID:26942567)
• this study provides the first demonstration that NNMT plays a role in the resistance to 5-fluorouracil in colorectal cancer cells (PMID:27323852)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:64002	ENSDARG00000086998
mus_musculus	Nnmt	ENSMUSG00000032271
rattus_norvegicus	Nnmt	ENSRNOG00000005930
caenorhabditis_elegans		WBGENE00011573
caenorhabditis_elegans		WBGENE00015124
caenorhabditis_elegans		WBGENE00018340

Paralogs (2): PNMT (ENSG00000141744), INMT (ENSG00000241644)

Protein

Protein identifiers

Nicotinamide N-methyltransferase — P40261 (reviewed: P40261)

All UniProt accessions (2): B0YJ53, P40261

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the N-methylation of nicotinamide using the universal methyl donor S-adenosyl-L-methionine to form N1-methylnicotinamide and S-adenosyl-L-homocysteine, a predominant nicotinamide/vitamin B3 clearance pathway. Plays a central role in regulating cellular methylation potential, by consuming S-adenosyl-L-methionine and limiting its availability for other methyltransferases. Actively mediates genome-wide epigenetic and transcriptional changes through hypomethylation of repressive chromatin marks, such as H3K27me3. In a developmental context, contributes to low levels of the repressive histone marks that characterize pluripotent embryonic stem cell pre-implantation state. Acts as a metabolic regulator primarily on white adipose tissue energy expenditure as well as hepatic gluconeogenesis and cholesterol biosynthesis. In white adipocytes, regulates polyamine flux by consuming S-adenosyl-L-methionine which provides for propylamine group in polyamine biosynthesis, whereas by consuming nicotinamide controls NAD(+) levels through the salvage pathway. Via its product N1-methylnicotinamide regulates protein acetylation in hepatocytes, by repressing the ubiquitination and increasing the stability of SIRT1 deacetylase. Can also N-methylate other pyridines structurally related to nicotinamide and play a role in xenobiotic detoxification.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Tissue specificity. Predominantly expressed in the liver. A lower expression is seen in the kidney, lung, skeletal muscle, placenta and heart. Not detected in the brain or pancreas.

Post-translational modifications. Deiminated by PADI1 and PADI2.

Activity regulation. Inactivated by deimination on Arg-132.

Pathway. Cofactor metabolism. Amino-acid degradation.

Miscellaneous. Prominently expressed in the stroma of high-grade serous carcinomas. In tumorigenesis, regulates the epigenetic reprograming of cancer cells associated with increased cell migration and metastasis.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.

RefSeq proteins (4): NP_001358974, NP_001358975, NP_001358976, NP_006160* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000940	NNMT_TEMT_trans	Family
IPR025820	NNMT/PNMT/TEMT_CS	Conserved_site
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR053384	SAM-dep_methyltransferase	Family

Pfam: PF01234

Enzyme classification (BRENDA):

• EC 2.1.1.1 — nicotinamide N-methyltransferase (BRENDA: 7 organisms, 35 substrates, 183 inhibitors, 46 Km, 23 kcat entries)

Substrate kinetics (BRENDA)

15 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NICOTINAMIDE	0.003–11.8	15
S-ADENOSYL-L-METHIONINE	0.0018–3.5	13
QUINOLINE	0.01–1.3	3
ISOQUINOLINE	0.087–1.5	2
1,2,3,4-TETRAHYDROISOQUINOLINE	0.2	1
2-METHOXYPYRIDINE	0.548	1
2-METHYLPYRIDINE	2.029	1
3-ACETYLPYRIDINE	0.727	1
4-METHYLNICOTINAMIDE	0.335	1
4-PHENYLPYRIDINE	0.125	1
NICOTINIMIDAMIDE	1.326	1
NORHARMAN	0.09	1
QUINOLINE 3-CARBOXAMIDE	0.364	1
TETRAHYDROISOQUINOLINE	0.613	1
THIONICOTINAMIDE	0.111	1

Catalyzed reactions (Rhea), 1 shown:

• nicotinamide + S-adenosyl-L-methionine = 1-methylnicotinamide + S-adenosyl-L-homocysteine (RHEA:23884)

UniProt features (51 total): strand 13, helix 12, binding site 10, mutagenesis site 8, modified residue 4, turn 3, chain 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9GVW	X-RAY DIFFRACTION	1.24
9H4Z	X-RAY DIFFRACTION	1.41
9GVM	X-RAY DIFFRACTION	1.67
7WMT	X-RAY DIFFRACTION	1.77
9H5E	X-RAY DIFFRACTION	1.9
7EGU	X-RAY DIFFRACTION	1.9
9H5O	X-RAY DIFFRACTION	1.9
9GWA	X-RAY DIFFRACTION	2
21LN	X-RAY DIFFRACTION	2.01
21NL	X-RAY DIFFRACTION	2.01
2IIP	X-RAY DIFFRACTION	2.05
7EI2	X-RAY DIFFRACTION	2.08
7RKL	X-RAY DIFFRACTION	2.08
7SOK	X-RAY DIFFRACTION	2.08
6ORR	X-RAY DIFFRACTION	2.25
21NJ	X-RAY DIFFRACTION	2.26
7NBJ	X-RAY DIFFRACTION	2.27
6CHH	X-RAY DIFFRACTION	2.3
6PVE	X-RAY DIFFRACTION	2.3
7BKG	X-RAY DIFFRACTION	2.33
21JX	X-RAY DIFFRACTION	2.34
9ATV	X-RAY DIFFRACTION	2.41
7NBQ	X-RAY DIFFRACTION	2.48
5YJF	X-RAY DIFFRACTION	2.49
7EHZ	X-RAY DIFFRACTION	2.5
7WMC	X-RAY DIFFRACTION	2.55
6PVS	X-RAY DIFFRACTION	2.58
7ET7	X-RAY DIFFRACTION	2.61
7NBM	X-RAY DIFFRACTION	2.69
3ROD	X-RAY DIFFRACTION	2.72

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40261-F1	96.11	0.94

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 (10): 20; 213; 25; 63; 69; 85; 90; 142–143; 163; 197

Post-translational modifications (4): 18, 39, 132, 181

Mutagenesis-validated functional residues (8):

Position	Phenotype
18	has no effect on n-methyltransferase activity.
20	loss of n-methyltransferase activity.
20	decreases n-methyltransferase activity.
132	loss of n-methyltransferase activity like its citrullinated counterpart.
181	has no effect on n-methyltransferase activity.
197	loss of n-methyltransferase activity.
201	has no effect on n-methyltransferase activity.
213	has no effect on n-methyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-156581	Methylation
R-HSA-196807	Nicotinate metabolism
R-HSA-2408508	Metabolism of ingested SeMet, Sec, MeSec into H2Se

MSigDB gene sets: 283 (showing top): MODULE_52, REACTOME_BIOLOGICAL_OXIDATIONS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MCLACHLAN_DENTAL_CARIES_UP, GNF2_GSTM1, GOBP_REGULATION_OF_PROTEIN_DEACETYLATION, GNF2_HPN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_MACROMOLECULE_DEACYLATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, KYNG_DNA_DAMAGE_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (7): nicotinamide metabolic process (GO:0006769), NAD+ catabolic process (GO:0019677), methylation (GO:0032259), positive regulation of gluconeogenesis (GO:0045722), positive regulation of protein deacetylation (GO:0090312), nicotinate metabolic process (GO:1901847), NAD+ biosynthetic process via the salvage pathway (GO:0034355)

GO Molecular Function (5): nicotinamide N-methyltransferase activity (GO:0008112), pyridine N-methyltransferase activity (GO:0030760), methyltransferase activity (GO:0008168), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Metabolism of water-soluble vitamins and cofactors	1
Selenoamino acid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
alkaloid metabolic process	2
pyridine-containing compound metabolic process	2
S-adenosylmethionine-dependent methyltransferase activity	2
cellular anatomical structure	2
purine nucleotide catabolic process	1
pyridine nucleotide catabolic process	1
NAD+ metabolic process	1
metabolic process	1
gluconeogenesis	1
regulation of gluconeogenesis	1
positive regulation of biosynthetic process	1
positive regulation of glucose metabolic process	1
protein deacetylation	1
positive regulation of protein modification process	1
regulation of protein deacetylation	1
monocarboxylic acid metabolic process	1
NAD+ biosynthetic process	1
pyridine nucleotide salvage	1
purine nucleotide salvage	1
N-methyltransferase activity	1
transferase activity, transferring one-carbon groups	1
methyltransferase activity	1
catalytic activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NNMT	MTHFR	P42898	725
NNMT	NAMPT	P43490	661
NNMT	STAT3	P40763	532
NNMT	EGFR	P00533	510
NNMT	GNMT	Q14749	507
NNMT	AOX1	Q06278	507
NNMT	LCP1	P13796	503
NNMT	IL6	P05231	492
NNMT	NMNAT1	Q9HAN9	480
NNMT	SIRT1	Q96EB6	447
NNMT	GSK3B	P49841	447
NNMT	ACSL1	P33121	423
NNMT	CXCL8	P10145	422
NNMT	AXIN1	O15169	420
NNMT	NMNAT2	Q9BZQ4	419

IntAct

5 interactions, top by confidence:

A	B	Type	Score
	TK2	psi-mi:“MI:0915”(physical association)	0.400
NNMT	ATF6	psi-mi:“MI:0915”(physical association)	0.370
BMF	NNMT	psi-mi:“MI:0915”(physical association)	0.370
PA	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): GLOD4 (Co-fractionation), NNMT (Co-fractionation), NNMT (Co-fractionation), NNMT (Affinity Capture-MS), NNMT (Affinity Capture-MS), NNMT (Proximity Label-MS), NNMT (Affinity Capture-MS), NNMT (Proximity Label-MS), NNMT (Affinity Capture-MS), NNMT (Affinity Capture-MS), NNMT (Proximity Label-MS), NNMT (Proximity Label-MS), NNMT (Affinity Capture-MS), NNMT (Proximity Label-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A0A1W2PQ27, A0A1W2PQ64, A0A1W2PQC6, A0A1W2PQD8, A0A1W2PQJ5, A0A1W2PR75, A2AV36, A4QN59, A6QQV6, D4A1F2, F1RA39, G5E8F4, J9SQF3, O00142, O42868, O55239, O95050, O95932, O97972, P0CR76, P0CR77, P10938, P40261, P40936, P53538, Q01841, Q22453, Q32LP9, Q4R7D0, Q566Y1, Q5M9G7, Q5RFR7, Q5U4E8, Q5XG58, Q62160, Q6C195, Q6CQ61, Q6DE00, Q6FMU7, Q6PCI6

Diamond homologs: A0A5F8AH41, O55239, O95050, O97972, P10937, P10938, P11086, P40261, P40935, P40936, Q06AU9, Q06AV1, Q5RFR7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

872 predictions. Top by Δscore:

Variant	Effect	Δscore
11:114270453:GTATC:G	donor_gain	0.9900
11:114270468:G:GT	donor_gain	0.9900
11:114297941:A:AG	acceptor_gain	0.9900
11:114297942:C:G	acceptor_gain	0.9900
11:114297944:A:AG	acceptor_gain	0.9900
11:114297949:A:AG	acceptor_gain	0.9900
11:114297950:G:GG	acceptor_gain	0.9900
11:114298118:TCCC:T	donor_gain	0.9900
11:114298119:CCCC:C	donor_gain	0.9900
11:114298126:G:GA	donor_gain	0.9900
11:114312043:A:AG	acceptor_gain	0.9900
11:114312044:G:GG	acceptor_gain	0.9900
11:114270458:G:GG	donor_gain	0.9800
11:114270470:A:T	donor_gain	0.9800
11:114297946:TCCA:T	acceptor_loss	0.9800
11:114297947:CCA:C	acceptor_loss	0.9800
11:114297948:CA:C	acceptor_loss	0.9800
11:114297949:AGAC:A	acceptor_gain	0.9800
11:114297950:GACG:G	acceptor_gain	0.9800
11:114298081:G:GT	donor_gain	0.9800
11:114312039:TTTCA:T	acceptor_loss	0.9800
11:114312040:TTCA:T	acceptor_loss	0.9800
11:114312043:A:AC	acceptor_loss	0.9800
11:114312044:G:GA	acceptor_loss	0.9800
11:114312044:GA:G	acceptor_gain	0.9800
11:114262838:C:CA	acceptor_gain	0.9700
11:114262838:C:G	acceptor_gain	0.9700
11:114297950:GAC:G	acceptor_gain	0.9700
11:114298106:GCCTT:G	donor_gain	0.9700
11:114298131:C:G	donor_gain	0.9700

AlphaMissense

1723 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:114312166:A:C	S162R	0.984
11:114312168:C:A	S162R	0.984
11:114312168:C:G	S162R	0.984
11:114298115:T:A	W107R	0.976
11:114298115:T:C	W107R	0.976
11:114298028:T:C	F78L	0.975
11:114298030:T:A	F78L	0.975
11:114298030:T:G	F78L	0.975
11:114298085:T:A	W97R	0.974
11:114298085:T:C	W97R	0.974
11:114312313:T:C	F211L	0.967
11:114312315:C:A	F211L	0.967
11:114312315:C:G	F211L	0.967
11:114296599:T:C	F15L	0.963
11:114296601:T:A	F15L	0.963
11:114296601:T:G	F15L	0.963
11:114298109:T:C	F105L	0.955
11:114298111:T:A	F105L	0.955
11:114298111:T:G	F105L	0.955
11:114298017:C:A	A74D	0.949
11:114298117:G:C	W107C	0.948
11:114298117:G:T	W107C	0.948
11:114312086:T:A	V135D	0.948
11:114312177:T:G	C165W	0.948
11:114296569:T:C	F5L	0.946
11:114296571:C:A	F5L	0.946
11:114296571:C:G	F5L	0.946
11:114297990:G:A	G65D	0.939
11:114312159:C:G	C159W	0.938
11:114296701:T:C	F49L	0.937

dbSNP variants (sampled 300 via entrez): RS1000017941 (11:114308625 T>A), RS1000039911 (11:114266005 A>T), RS1000098068 (11:114261348 G>A), RS1000153118 (11:114273228 C>A), RS1000160177 (11:114261782 T>G), RS1000225329 (11:114294801 GA>G,GAA), RS1000275502 (11:114278936 G>T), RS1000292553 (11:114309693 A>T), RS1000460533 (11:114283912 C>A), RS1000472528 (11:114258067 G>A), RS1000494408 (11:114308392 C>T), RS1000494484 (11:114256910 G>A,C,T), RS1000524488 (11:114258260 C>G,T), RS1000580651 (11:114283648 T>A), RS1000594298 (11:114303049 T>A)

Disease associations

OMIM: gene MIM:600008 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000088_4	Volumetric brain MRI	3.000000e-06
GCST002875_44	Diisocyanate-induced asthma	2.000000e-07
GCST005212_3	Asthma	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004868	volumetric brain MRI
EFO:0006995	response to diisocyanate

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2346486 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,885 (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
CHEMBL1214186	SINEFUNGIN	2	2,165
CHEMBL71733	TRIGONELLAMIDE	2	720

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 2.1.1.- Methyltransferases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
NNMT inhibitor 14 [PMID: 35904556]	Inhibition	6.4	pIC50

Binding affinities (BindingDB)

12 measured of 18 human assays (18 total across all organisms); most potent 12 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5178360	IC50	100 nM
CHEMBL5191549	IC50	160 nM
CHEMBL5186497	IC50	270 nM
CHEMBL5200510	IC50	390 nM
CHEMBL5182917	IC50	2100 nM
YUANHUADINE	IC50	4000 nM
CHEMBL5202309	IC50	45500 nM
1,2,3,4-tetrahydroisoquinoline	KI	4.7e+07 nM
thionicotinamide	KI	6.6e+07 nM
quinoline 3-carboxamide	KI	9.7e+07 nM
quinoline	KI	1.02e+08 nM
isoquinoline	KI	2.02e+08 nM

ChEMBL bioactivities

250 potent at pChembl≥5 of 299 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.82	IC50	0.15	nM	CHEMBL4867273
9.72	Ki	0.1905	nM	CHEMBL4553052
9.62	Ki	0.2399	nM	CHEMBL4580446
9.40	IC50	0.4	nM	CHEMBL4859806
9.33	IC50	0.47	nM	CHEMBL4847740
9.30	Ki	0.5	nM	CHEMBL4591248
9.30	Ki	0.5012	nM	CHEMBL4591248
9.03	IC50	0.93	nM	CHEMBL4857394
8.96	IC50	1.1	nM	CHEMBL4878738
8.96	IC50	1.1	nM	CHEMBL5194905
8.92	Ki	1.2	nM	CHEMBL5408922
8.80	Ki	1.6	nM	CHEMBL4445337
8.80	Ki	1.6	nM	CHEMBL5433732
8.73	Ki	1.862	nM	CHEMBL4455627
8.72	Ki	1.9	nM	CHEMBL4445337
8.72	IC50	1.9	nM	CHEMBL4872872
8.59	Ki	2.6	nM	CHEMBL4445337
8.58	Ki	2.63	nM	CHEMBL4449355
8.51	Ki	3.1	nM	CHEMBL5407922
8.47	Ki	3.388	nM	CHEMBL4519184
8.43	IC50	3.7	nM	CHEMBL5189197
8.33	Ki	4.677	nM	CHEMBL4435488
8.30	Ki	5.012	nM	CHEMBL4457046
8.24	IC50	5.8	nM	CHEMBL4856854
8.23	Ki	5.9	nM	CHEMBL5420435
8.17	Ki	6.8	nM	CHEMBL4445337
8.17	Ki	6.761	nM	CHEMBL4473236
8.07	Ki	8.5	nM	CHEMBL5420435
8.05	Ki	8.913	nM	CHEMBL4587553
8.00	IC50	10	nM	CHEMBL5173204
8.00	IC50	10	nM	CHEMBL4445337
7.92	IC50	12	nM	CHEMBL4866114
7.92	IC50	12	nM	CHEMBL5220889
7.89	IC50	13	nM	CHEMBL5172454
7.85	IC50	14	nM	CHEMBL4853328
7.85	IC50	14	nM	CHEMBL4848464
7.80	Ki	16	nM	CHEMBL4476197
7.80	IC50	16	nM	CHEMBL5187248
7.77	Ki	16.98	nM	CHEMBL4565052
7.72	Ki	19	nM	CHEMBL5408922
7.70	IC50	20	nM	CHEMBL5220024
7.67	Kd	21.23	nM	CHEMBL5189197
7.64	IC50	23	nM	CHEMBL5221106
7.64	IC50	23	nM	CHEMBL5408922
7.60	IC50	25	nM	CHEMBL5218573
7.55	IC50	28	nM	CHEMBL4868588
7.54	IC50	29	nM	CHEMBL5437399
7.50	IC50	32	nM	CHEMBL5433732
7.49	Ki	32.36	nM	CHEMBL4435314
7.45	Ki	35.48	nM	CHEMBL4584198

PubChem BioAssay actives

233 with measured affinity, of 6100 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
(3S,9S,12S,15S,21S,27R,30S,33S)-9-(4-aminobutyl)-21-benzyl-30-[[4-(4-carbamoylphenyl)phenyl]methyl]-12-(2-methylpropyl)-2,8,11,14,20,23,29,32-octaoxo-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0001	uM
(2S,5S)-2-amino-5-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(3-carbamoyl-4-chlorophenyl)hept-6-ynoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0002	uM
(2S,6S)-2-amino-6-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-8-(3-carbamoylphenyl)oct-7-ynoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0002	uM
4-[4-[[(3S,9S,12S,15S,17S,21S,30S,33S)-21-benzyl-9-[4-(dimethylamino)butyl]-12-(2,2-dimethylpropyl)-5,5-difluoro-22-methyl-2,8,11,14,20,23,29,32-octaoxo-17-phenyl-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-trien-30-yl]methyl]phenyl]benzamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0004	uM
(2S,5S)-2-amino-5-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(3-carbamoylphenyl)hept-6-ynoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0005	uM
(3S,9S,12S,15S,17S,21S,27R,30S,33S)-9-(4-aminobutyl)-21-benzyl-30-[(4-carbamoylphenyl)methyl]-12-(2-methylpropyl)-2,8,11,14,20,23,29,32-octaoxo-17-phenyl-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0005	uM
(3S,9S,12S,15S,21S,27R,30S,33S)-9-(4-aminobutyl)-21-benzyl-30-[[4-(3-carbamoylphenyl)phenyl]methyl]-12-(2-methylpropyl)-2,8,11,14,20,23,29,32-octaoxo-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0009	uM
(3S,9S,12S,15S,21S,27R,30S,33S)-9-(5-aminopentyl)-21-benzyl-30-[(4-carbamoylphenyl)methyl]-22-methyl-12-(2-methylpropyl)-2,8,11,14,20,23,29,32-octaoxo-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0011	uM
[(2R,4S)-4-[5-(aminomethyl)-3-methylpyrazol-1-yl]-2-[1-[(4-chlorophenyl)methyl]-5-methylindol-2-yl]pyrrolidin-1-yl]-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)methanone	1885880: Inhibition of N-terminal 6His-tagged full length human recombinant NNMT (1 to 264 residues) expressed in Escherichia coli BL21 (DE3) cells using S-adenosyl-L-methionine and NAM as substrate incubated for 22 to 24 hrs by RapidFire Mass Spectrometry	ic50	0.0011	uM
5-[3-[acetyl-[[(1R,2R,3S,4R)-4-(4-chloropyrrolo[2,3-d]pyrimidin-7-yl)-2,3-dihydroxycyclopentyl]methyl]amino]prop-1-ynyl]-2-chlorobenzamide	2010643: Binding affinity to full-length wild-type human NNMT (1 to 270 residues) expressed in Escherichia coli BL21(DE3) cells assessed as apparent inhibition constant preincubated for 30 mins followed by nicotinamide addition by fluorescence-based SAHH-coupled assay	ki	0.0012	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-(3-carbamoylphenyl)prop-2-ynyl]amino]butanoic acid	1527769: Inhibition of full-length human N-terminal TEV cleavage site NNMT (1 to 270 residues) expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL cells using nicotinamide as substrate preincubated for 120 mins in presence of AdoMet followed by substrate addition by SAHH enzyme coupled fluorescence assay based Morrison equation analysis	ki	0.0016	uM
3-[3-[acetyl-[[(1R,2R,3S,4R)-4-(4-chloropyrrolo[2,3-d]pyrimidin-7-yl)-2,3-dihydroxycyclopentyl]methyl]amino]prop-1-ynyl]-4-chlorobenzamide	2010643: Binding affinity to full-length wild-type human NNMT (1 to 270 residues) expressed in Escherichia coli BL21(DE3) cells assessed as apparent inhibition constant preincubated for 30 mins followed by nicotinamide addition by fluorescence-based SAHH-coupled assay	ki	0.0016	uM
(2S,5S)-2-amino-5-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(3-carbamoyl-4-fluorophenyl)hept-6-ynoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0019	uM
4-[4-[[(3S,9S,16S,19S,21S,25S,34S,37S)-25-benzyl-16-(2,2-dimethylpropyl)-5,5-difluoro-26-methyl-2,8,15,18,24,27,33,36-octaoxo-21-phenyl-29-thia-1,7,14,17,23,26,32,35-octazahexacyclo[35.8.0.03,7.09,14.019,23.039,44]pentatetraconta-39,41,43-trien-34-yl]methyl]phenyl]benzamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0019	uM
(2S,5S)-2-amino-5-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-[3-carbamoyl-4-(trifluoromethyl)phenyl]hept-6-ynoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0026	uM
5-[3-[acetyl-[[(1R,2R,3S,4R)-4-(4-chloropyrrolo[2,3-d]pyrimidin-7-yl)-2,3-dihydroxycyclopentyl]methyl]amino]prop-1-ynyl]-2-methylbenzamide	2010653: Binding affinity to full-length recombinant human NNMT expressed in Escherichia coli BL21(DE3) cells assessed as apparent inhibition constant using nicotinamide as substrate preincubated for 30 mins followed by substrate addition in presence of SAM by fluorescence-based SAHH-coupled assay	ki	0.0031	uM
(2S,5S)-2-amino-5-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(3-carbamoyl-4-methylphenyl)hept-6-ynoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0034	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[(E)-3-(4-cyanophenyl)prop-2-enyl]amino]butanoic acid	1847407: Inhibition of recombinant NNMT (unknown origin) assessed as reduction in MNA concentration incubated for 10 mins measured after 30 mins by LC-MS/MS-MRM analysis	ic50	0.0037	uM
(2S,5S)-2-amino-5-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(3-carbamoylphenyl)heptanoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0047	uM
(2S,5S)-2-amino-5-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(5-carbamoyl-3-pyridinyl)hept-6-ynoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0050	uM
(3S,9S,12S,15S,17R,21S,27R,30S,33S)-9-(4-aminobutyl)-21-benzyl-30-[(4-carbamoylphenyl)methyl]-12-(2-methylpropyl)-2,8,11,14,20,23,29,32-octaoxo-17-(trifluoromethyl)-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0058	uM
3-[3-[acetyl-[[(1R,2R,3S,4R)-4-(4-chloropyrrolo[2,3-d]pyrimidin-7-yl)-2,3-dihydroxycyclopentyl]methyl]amino]prop-1-ynyl]benzamide	2010643: Binding affinity to full-length wild-type human NNMT (1 to 270 residues) expressed in Escherichia coli BL21(DE3) cells assessed as apparent inhibition constant preincubated for 30 mins followed by nicotinamide addition by fluorescence-based SAHH-coupled assay	ki	0.0059	uM
(2S,5S)-2-amino-5-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(6-carbamoyl-2-pyridinyl)hept-6-ynoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0068	uM
(2S,5S)-2-amino-5-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(2-carbamoyl-4-pyridinyl)hept-6-ynoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0089	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-(4-nitrophenyl)prop-2-enyl]amino]butanoic acid	1847407: Inhibition of recombinant NNMT (unknown origin) assessed as reduction in MNA concentration incubated for 10 mins measured after 30 mins by LC-MS/MS-MRM analysis	ic50	0.0100	uM
(3S,6S,9S,12S,18S,24R,30S,33S,36S)-30-(4-aminobutyl)-N-(2-amino-2-oxoethyl)-3,18-dibenzyl-6-[(2S)-butan-2-yl]-33-[3-(diaminomethylideneamino)propyl]-9-(2-methylpropyl)-2,5,8,11,17,20,26,29,32,35-decaoxo-22-thia-1,4,7,10,16,19,25,28,31,34-decazatricyclo[34.3.0.012,16]nonatriacontane-24-carboxamide	1751540: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 2 hrs by RapidFire Mass spectroscopy	ic50	0.0120	uM
(2R)-2,4-dimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-carboxamide	1918422: Inhibition of human NNMT in human K562 cells measured after 24 hrs by quantitative mass spectrometry	ic50	0.0120	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[(E)-3-(3-carbamoylphenyl)prop-2-enyl]amino]butanoic acid	1847407: Inhibition of recombinant NNMT (unknown origin) assessed as reduction in MNA concentration incubated for 10 mins measured after 30 mins by LC-MS/MS-MRM analysis	ic50	0.0130	uM
(3S,9S,12S,15S,21S,27R,30S,33S)-9-(4-aminobutyl)-21-benzyl-30-[(4-carbamoylphenyl)methyl]-17,17-difluoro-12-(2-methylpropyl)-2,8,11,14,20,23,29,32-octaoxo-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0140	uM
(3S,9S,12S,15S,21S,27R,30S,33S)-9-(4-aminobutyl)-21-benzyl-30-[(4-carbamoylphenyl)methyl]-5,5-difluoro-12-(2-methylpropyl)-2,8,11,14,20,23,29,32-octaoxo-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0140	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-(3-carbamoyl-4-methylphenyl)prop-2-ynyl]amino]butanoic acid	1527765: Inhibition of full-length human N-terminal TEV cleavage site NNMT (1 to 270 residues) expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL cells using nicotinamide as substrate preincubated for 10 mins in presence of AdoMet followed by substrate addition by fluorescence based SAHH-coupled assay	ki	0.0160	uM
[(2R,4S)-4-[2-(aminomethyl)imidazol-1-yl]-2-[1-[(4-chlorophenyl)methyl]-5-methylindol-2-yl]pyrrolidin-1-yl]-(1H-pyrrolo[2,3-b]pyridin-5-yl)methanone	1885880: Inhibition of N-terminal 6His-tagged full length human recombinant NNMT (1 to 264 residues) expressed in Escherichia coli BL21 (DE3) cells using S-adenosyl-L-methionine and NAM as substrate incubated for 22 to 24 hrs by RapidFire Mass Spectrometry	ic50	0.0160	uM
3-[(3S,6S)-6,7-diamino-3-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-oxohept-1-ynyl]benzamide	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0170	uM
(2R,3S)-2,3-dimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-carboxamide	1918421: Inhibition of human NNMT measured after 20 mins by luminescence based methyltransferase assay	ic50	0.0200	uM
4-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-carboxamide	1918422: Inhibition of human NNMT in human K562 cells measured after 24 hrs by quantitative mass spectrometry	ic50	0.0230	uM
4-methyl-6-(methylamino)pyridine-3-carboxamide	1918422: Inhibition of human NNMT in human K562 cells measured after 24 hrs by quantitative mass spectrometry	ic50	0.0250	uM
(3S,9S,12S,15S,21S,27R,30S,33S)-21-benzyl-30-[(4-carbamoylphenyl)methyl]-9-[3-(diaminomethylideneamino)propyl]-12-[(4-hydroxyphenyl)methyl]-2,8,11,14,20,23,29,32-octaoxo-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0280	uM
5-[3-[acetyl-[[(1R,2R,3S,4R)-4-(4-chloropyrrolo[2,3-d]pyrimidin-7-yl)-2,3-dihydroxycyclopentyl]methyl]amino]prop-1-ynyl]-2-bromobenzamide	2010651: Inhibition of full-length recombinant human NNMT expressed in Escherichia coli BL21(DE3) cells using nicotinamide as substrate preincubated for 30 mins followed by substrate addition by fluorescence-based SAHH-coupled assay	ic50	0.0290	uM
(2S,5S)-2-amino-5-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(6-carbamoyl-1,3-benzodioxol-4-yl)hept-6-ynoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0324	uM
(2S,5S)-2-amino-5-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(4-carbamoyl-2-pyridinyl)hept-6-ynoic acid	1616783: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay	ki	0.0355	uM
(3S,9S,12S,15S,21S,27R,30S,33S)-9-(4-aminobutyl)-21-benzyl-30-[(4-carbamoylphenyl)methyl]-12-(2,2-dimethylpropyl)-22-methyl-2,8,11,14,20,23,29,32-octaoxo-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0360	uM
(2R)-2-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-carboxamide	1918422: Inhibition of human NNMT in human K562 cells measured after 24 hrs by quantitative mass spectrometry	ic50	0.0380	uM
(3S,9S,12S,15S,21S,27R,30S,33S)-21-benzyl-30-[(4-carbamoylphenyl)methyl]-9-[3-(diaminomethylideneamino)propyl]-22-methyl-12-(2-methylpropyl)-2,8,11,14,20,23,29,32-octaoxo-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0420	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-(3-carbamoylphenyl)propyl]amino]butanoic acid	1527765: Inhibition of full-length human N-terminal TEV cleavage site NNMT (1 to 270 residues) expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL cells using nicotinamide as substrate preincubated for 10 mins in presence of AdoMet followed by substrate addition by fluorescence based SAHH-coupled assay	ki	0.0430	uM
(3S,9S,12S,15S,17S,21S,27R,30S,33S)-9-(4-aminobutyl)-21-benzyl-30-[(4-carbamoylphenyl)methyl]-12-(2-methylpropyl)-2,8,11,14,20,23,29,32-octaoxo-17-(trifluoromethyl)-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0450	uM
(2R)-4-chloro-2-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-carboxamide	1918421: Inhibition of human NNMT measured after 20 mins by luminescence based methyltransferase assay	ic50	0.0480	uM
(2S)-2-amino-4-[3-(3-carbamoylphenyl)prop-2-ynyl-[[(1R,2R,3S,4R)-4-(4-chloropyrrolo[2,3-d]pyrimidin-7-yl)-2,3-dihydroxycyclopentyl]methyl]amino]-4-oxobutanoic acid	2010650: Binding affinity to full-length recombinant human NNMT expressed in Escherichia coli BL21(DE3) cells assessed as inhibition constant preincubated for 30 mins followed by FP probe addition measured after 30 mins by fluorescence polarization competition assay	ki	0.0490	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-(3-carbamoyl-4-methylphenyl)propyl]amino]butanoic acid	1527765: Inhibition of full-length human N-terminal TEV cleavage site NNMT (1 to 270 residues) expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL cells using nicotinamide as substrate preincubated for 10 mins in presence of AdoMet followed by substrate addition by fluorescence based SAHH-coupled assay	ki	0.0510	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-(5-carbamoyl-2-methoxyphenyl)prop-2-ynyl]amino]butanoic acid	1527765: Inhibition of full-length human N-terminal TEV cleavage site NNMT (1 to 270 residues) expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL cells using nicotinamide as substrate preincubated for 10 mins in presence of AdoMet followed by substrate addition by fluorescence based SAHH-coupled assay	ki	0.0520	uM
(3S,9S,12S,15S,21S,27R,30S,33S)-9-(4-aminobutyl)-21-benzyl-30-[(4-carbamoylphenyl)methyl]-12-(2-methylpropyl)-2,8,11,14,20,23,29,32-octaoxo-25-thia-1,7,10,13,19,22,28,31-octazapentacyclo[31.8.0.03,7.015,19.035,40]hentetraconta-35,37,39-triene-27-carboxamide	1751535: Inhibition of human recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy	ic50	0.0520	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	5
sodium arsenite	increases expression, affects binding, increases reaction, decreases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression	2
cobaltous chloride	decreases expression	2
potassium chromate(VI)	decreases expression, increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	increases abundance, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression, increases expression	2
testosterone enanthate	affects expression	1
deoxynivalenol	decreases expression, increases reaction, increases expression	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
heliotrine	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
seocalcitol	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1

ChEMBL screening assays

108 unique, capped per target: 108 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2350640	Binding	Inhibition of recombinant full length human NNMT measured for 30 mins by SAHH-coupled fluorescence assay	Bromo-deaza-SAH: a potent and selective DOT1L inhibitor. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1YQ	Abcam HeLa NNMT KO	Cancer cell line	Female

Clinical trials (associated diseases)

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