PNMT
gene geneOn this page
Summary
PNMT (phenylethanolamine N-methyltransferase, HGNC:9160) is a protein-coding gene on chromosome 17q12, encoding Phenylethanolamine N-methyltransferase (P11086). Catalyzes the transmethylation of nonepinephrine (noradrenaline) to form epinephrine (adrenaline), using S-adenosyl-L-methionine as the methyl donor.
The product of this gene catalyzes the last step of the catecholamine biosynthesis pathway, which methylates norepinephrine to form epinephrine (adrenaline). The enzyme also has beta-carboline 2N-methyltransferase activity. This gene is thought to play a key step in regulating epinephrine production. Alternatively spliced transcript variants have been found for this gene.
Source: NCBI Gene 5409 — RefSeq curated summary.
At a glance
- GWAS associations: 13
- Clinical variants (ClinVar): 56 total
- Druggable target: yes — 1 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_002686
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:9160 |
| Approved symbol | PNMT |
| Name | phenylethanolamine N-methyltransferase |
| Location | 17q12 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000141744 |
| Ensembl biotype | protein_coding |
| OMIM | 171190 |
| Entrez | 5409 |
Gene structure
Transcript identifiers
Ensembl transcripts: 3 — 3 protein_coding
ENST00000269582, ENST00000394246, ENST00000581428
RefSeq mRNA: 1 — MANE Select: NM_002686
NM_002686
CCDS: CCDS11343
Canonical transcript exons
ENST00000269582 — 3 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000950701 | 39668453 | 39668677 |
| ENSE00000950703 | 39669951 | 39670475 |
| ENSE00003663493 | 39669629 | 39669836 |
Expression profiles
Bgee: expression breadth ubiquitous, 182 present calls, max score 94.20.
FANTOM5 (CAGE): breadth broad, TPM avg 1.3771 / max 215.1365, expressed in 262 samples.
FANTOM5 promoters (11 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 160615 | 0.3531 | 47 |
| 160611 | 0.2640 | 85 |
| 160616 | 0.1955 | 86 |
| 160609 | 0.1626 | 74 |
| 160608 | 0.1145 | 54 |
| 160613 | 0.1035 | 36 |
| 160607 | 0.0590 | 30 |
| 160612 | 0.0456 | 17 |
| 160610 | 0.0296 | 11 |
| 160614 | 0.0258 | 15 |
Top tissues by expression
276 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 94.20 | silver quality |
| nucleus accumbens | UBERON:0001882 | 91.22 | gold quality |
| caudate nucleus | UBERON:0001873 | 90.12 | gold quality |
| putamen | UBERON:0001874 | 89.41 | gold quality |
| right atrium auricular region | UBERON:0006631 | 87.07 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 86.76 | gold quality |
| cardiac atrium | UBERON:0002081 | 85.84 | gold quality |
| gastrocnemius | UBERON:0001388 | 85.77 | gold quality |
| right lung | UBERON:0002167 | 85.22 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 85.12 | silver quality |
| apex of heart | UBERON:0002098 | 84.84 | gold quality |
| substantia nigra | UBERON:0002038 | 84.42 | gold quality |
| muscle of leg | UBERON:0001383 | 84.14 | gold quality |
| medial globus pallidus | UBERON:0002477 | 83.82 | gold quality |
| hypothalamus | UBERON:0001898 | 83.69 | gold quality |
| pituitary gland | UBERON:0000007 | 83.35 | gold quality |
| adenohypophysis | UBERON:0002196 | 83.12 | gold quality |
| midbrain | UBERON:0001891 | 83.07 | gold quality |
| amygdala | UBERON:0001876 | 82.73 | gold quality |
| muscle organ | UBERON:0001630 | 82.62 | gold quality |
| triceps brachii | UBERON:0001509 | 82.48 | gold quality |
| dorsal motor nucleus of vagus nerve | UBERON:0002870 | 81.97 | gold quality |
| globus pallidus | UBERON:0001875 | 81.83 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 81.75 | gold quality |
| cervix squamous epithelium | UBERON:0006922 | 81.50 | gold quality |
| buccal mucosa cell | CL:0002336 | 80.62 | silver quality |
| heart left ventricle | UBERON:0002084 | 80.54 | gold quality |
| cingulate cortex | UBERON:0003027 | 80.53 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 80.32 | gold quality |
| cardiac ventricle | UBERON:0002082 | 80.22 | gold quality |
Single-cell (SCXA)
Detected in 3 experiment(s), a significant marker in 3.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-MTAB-10042 | yes | 174.37 |
| E-MTAB-7407 | yes | 151.44 |
| E-ANND-3 | no | 0.00 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): EGR1, HIF1A, MAZ, NR3C1, PITX2, SP1, TFAP2A, TFAP2B
Literature-anchored findings (GeneRIF, showing 25)
- Human PNMT has been crystallized in complex with an inhibitor and the cofactor product S-adenosyl-L-homocysteine and diffraction data measured from a cryocooled crystal extend to a resolution of 2.3 A. (PMID:11807261)
- pharmacologic and biochemical evidence of beta-carboline 2N-methyltransferase activity (PMID:11900856)
- Association between the phenylethanolamine N-methyltransferase gene and multiple sclerosis. (PMID:11958827)
- homozygosity/heterozygosity of the phenylethanolamine N-methyltransferase gene polymorphism was highly predictive of significant weight loss with sibutramine during the first 3 months of obesity treatment (PMID:12634439)
- genetic variants of PNMT may play a role in the development of essential hypertension. (PMID:14553966)
- Oncogenomic recombination hotspot around the PPP1R1B-STARD3-TCAP-PNMT-PERLD1-ERBB2-C17orf37-GRB7 amplicon at human chromosome 17q12 is closely linked to evolutionary recombination hotspot around the GSDML-GSDM locus. (PMID:15010812)
- Presence of local PNMT transcription in human heart after transplantation. (PMID:15848714)
- disulfide-linked dimers are as active as the monomeric enzyme indicating that the crystal structure of the protein is a valid target for inhibitor design. (PMID:15893506)
- Nicotinic stimuli appear to regulate expression of the epinephrine-synthesizing gene PNMT through a previously uncharacterized regulatory element. (PMID:15968085)
- Results suggest that PNMT catalyzes transfer of methyl to ligand amines only when “anchor” interactions, such as those identified for the beta-hydroxyls of p-octopamine and cis-AT, are present. (PMID:16363801)
- the differences in PNMT expression between normotensives and hypertensives are not determined by the polymorphisms in this gene, but rather by the interplay of gene expression regulators, which may vary among individuals (PMID:17645789)
- We examined the correlation between reward dependence (RD) trait, and 5 polymorphisms in genes of norepinephrine pathways. We found that rs3764351 in PNMT was significantly associated with reward dependence trait. (PMID:18702937)
- Haplotypes of the phenylethanolamine N-methyltransferase (PNMT), catechol-O-methyltransferase (COMT) have functionally important effects on alcohol-induced cardiovascular symptoms by affecting blood catecholamine levels. (PMID:18715275)
- The crystal structures illustrate the adaptability of the PNMT substrate binding site in accepting multi-fused ring systems, such as substituted norbornene, as well as noradrenochrome, the oxidation product of noradrenaline. (PMID:19570037)
- the reaction takes place via an SN2 mechanism with methyl transfer being rate-limiting (PMID:19733262)
- PNMT G-390A polymorphism is possibly associated with essential hypertension risk in male Chinese Han population. (PMID:19952402)
- In Caucasians, phenylethanolamine N-methyltransferase single nucleotide polymorphisms are associated with the development of acute kidney injury, disease severity, and in-hospital mortality. (PMID:20090367)
- PNMT variants in cis may interact with nuclear factors in trans to govern adrenergic activity. (PMID:20204374)
- The 2-SNP AA haplotype in the PNMT promoter is associated with decreased risk of essential hypertension in Han Chinese. (PMID:21866188)
- initial velocity studies on human PNMT in the absence and presence of product and dead end inhibitors. (PMID:24018397)
- PNMT underexpression is associated with malignant pheochromocytoma and paraganglioma. (PMID:27007161)
- Epistasis between phenylethanolamine N-methyltransferase and beta2-adrenergic receptor influences extracellular epinephrine level and associates with the susceptibility to allergic asthma. (PMID:31855300)
- The effect of transcutaneous electrical nerve stimulation (TENS) on pain control and phenylethanolamine-N-methyltransferase (PNMT) gene expression after cesarean section. (PMID:34933717)
- Overexpression of miR-375 and L-type Amino Acid Transporter 1 in Pheochromocytoma and Their Molecular and Functional Implications. (PMID:35269556)
- Composite paraganglioma-ganglioneuroma with atypical catecholamine profile and phenylethanolamine N-methyltransferase expression: a case report and literature review. (PMID:37952980)
Cross-species orthologs
6 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | pnmt | ENSDARG00000116039 |
| mus_musculus | Pnmt | ENSMUSG00000038216 |
| rattus_norvegicus | Pnmt | ENSRNOG00000046057 |
| caenorhabditis_elegans | WBGENE00011573 | |
| caenorhabditis_elegans | WBGENE00015124 | |
| caenorhabditis_elegans | WBGENE00018340 |
Paralogs (2): NNMT (ENSG00000166741), INMT (ENSG00000241644)
Protein
Protein identifiers
Phenylethanolamine N-methyltransferase — P11086 (reviewed: P11086)
Alternative names: Noradrenaline N-methyltransferase
All UniProt accessions (3): A8MT87, P11086, J3QRI3
UniProt curated annotations — full annotation on UniProt →
Function. Catalyzes the transmethylation of nonepinephrine (noradrenaline) to form epinephrine (adrenaline), using S-adenosyl-L-methionine as the methyl donor. Other substrates include phenylethanolamine and octopamine. Also methylates normetanephrine.
Activity regulation. Inhibited by methyl methanethiosulfonate, phenylglyoxal, tetranitromethane and diethyl pyrocarbonate. Inhibited by 4-oxo-1,4-dihydro-quinoline-3,7-dicarboxylic acid, 4-(benzo[d][1,3]dioxol-5-ylamino)-4-oxobutanoic acid and 1,4-diaminonaphthalene-2,6-disulfonic acid.
Pathway. Catecholamine biosynthesis; (R)-adrenaline biosynthesis; (R)-adrenaline from (R)-noradrenaline: step 1/1.
Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.
RefSeq proteins (1): NP_002677* (*=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 2.1.1.28 — phenylethanolamine N-methyltransferase (BRENDA: 11 organisms, 48 substrates, 244 inhibitors, 71 Km, 22 kcat entries)
Substrate kinetics (BRENDA)
20 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| S-ADENOSYL-L-METHIONINE | 0.0012–0.045 | 23 |
| PHENYLETHANOLAMINE | 0.07–2.05 | 18 |
| L-NOREPINEPHRINE | 0.015–0.101 | 4 |
| 3,4-DICHLOROPHENYLETHANOLAMINE | 0.0008–0.0016 | 3 |
| 3-TRIFLUOROMETHYLPHENYLETHANOLAMINE | 0.0005–0.055 | 3 |
| 3,4-DICHLOROPHENYLETHYLENEDIAMINE | 0.012–0.0131 | 2 |
| ANTI-9-AMINO-6-(TRIFLUOROMETHYL)BENZONORBORNENE | 0.0015–0.025 | 2 |
| D-NOREPINEPHRINE | 0.0297–0.109 | 2 |
| OCTOPAMINE | 0.0055 | 2 |
| 2-HYDROXYPHENYLETHANOLAMINE | 0.676 | 1 |
| 3,4-DIHYDROXYPHENYLETHANOLAMINE | 0.013 | 1 |
| 3-CHLORO-4-HYDROXYPHENYLETHANOLAMINE | 0.0024 | 1 |
| 3-HYDROXYPHENYLETHANOLAMINE | 0.089 | 1 |
| 3-METHOXY-4-HYDROXY-PHENYLETHANOLAMINE | 0.366 | 1 |
| 4-AMINOMETHYL-1,2,3,4-TETRAHYDROISOQUINOLINE | 0.047 | 1 |
Catalyzed reactions (Rhea), 4 shown:
- phenylethanolamine + S-adenosyl-L-methionine = N-methylphenylethanolamine + S-adenosyl-L-homocysteine + H(+) (RHEA:12176)
- (R)-noradrenaline + S-adenosyl-L-methionine = (R)-adrenaline + S-adenosyl-L-homocysteine + H(+) (RHEA:25269)
- (R)-octopamine + S-adenosyl-L-methionine = (R)-synephrine + S-adenosyl-L-homocysteine + H(+) (RHEA:70519)
- (R)-normetanephrine + S-adenosyl-L-methionine = (R)-metanephrine + S-adenosyl-L-homocysteine + H(+) (RHEA:70683)
UniProt features (53 total): helix 12, strand 11, binding site 10, sequence variant 9, mutagenesis site 5, turn 2, initiator methionine 1, chain 1, modified residue 1, sequence conflict 1
Structure
Experimental structures (PDB)
44 structures, top 30 by resolution.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 4MIK | X-RAY DIFFRACTION | 1.95 |
| 2G72 | X-RAY DIFFRACTION | 2 |
| 3KQS | X-RAY DIFFRACTION | 2 |
| 7TWU | X-RAY DIFFRACTION | 2.1 |
| 2G8N | X-RAY DIFFRACTION | 2.15 |
| 2AN3 | X-RAY DIFFRACTION | 2.2 |
| 2AN4 | X-RAY DIFFRACTION | 2.2 |
| 2G71 | X-RAY DIFFRACTION | 2.2 |
| 3KQY | X-RAY DIFFRACTION | 2.2 |
| 4MQ4 | X-RAY DIFFRACTION | 2.2 |
| 2OBF | X-RAY DIFFRACTION | 2.3 |
| 3HCC | X-RAY DIFFRACTION | 2.3 |
| 3KQV | X-RAY DIFFRACTION | 2.3 |
| 3KR1 | X-RAY DIFFRACTION | 2.3 |
| 3KR2 | X-RAY DIFFRACTION | 2.3 |
| 3HCD | X-RAY DIFFRACTION | 2.39 |
| 3KQT | X-RAY DIFFRACTION | 2.4 |
| 1HNN | X-RAY DIFFRACTION | 2.4 |
| 1YZ3 | X-RAY DIFFRACTION | 2.4 |
| 2G70 | X-RAY DIFFRACTION | 2.4 |
| 3HCA | X-RAY DIFFRACTION | 2.4 |
| 3HCB | X-RAY DIFFRACTION | 2.4 |
| 3KPU | X-RAY DIFFRACTION | 2.4 |
| 3KPV | X-RAY DIFFRACTION | 2.4 |
| 3KPW | X-RAY DIFFRACTION | 2.4 |
| 3KPY | X-RAY DIFFRACTION | 2.4 |
| 3KQM | X-RAY DIFFRACTION | 2.4 |
| 3KQO | X-RAY DIFFRACTION | 2.4 |
| 3KQP | X-RAY DIFFRACTION | 2.4 |
| 4DM3 | X-RAY DIFFRACTION | 2.4 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P11086-F1 | 94.64 | 0.92 |
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): 219; 267; 35; 40; 79–80; 85; 101; 106; 158–159; 181
Post-translational modifications (1): 7
Mutagenesis-validated functional residues (5):
| Position | Phenotype |
|---|---|
| 35 | strongly increases km for phenylethanolamine and s-adenosyl-l-methionine. |
| 185 | strongly reduced enzyme activity towards phenylethanolamine. increases affinity for s-adenosyl-l-methionine. |
| 185 | strongly reduced enzyme activity towards phenylethanolamine. decreases affinity for phenylethanolamine and s-adenosyl-l- |
| 219 | reduced enzyme activity towards phenylethanolamine. decreases affinity for phenylethanolamine 6-fold. decreases affinity |
| 267 | strongly reduced enzyme activity towards phenylethanolamine. decreases affinity for phenylethanolamine 200-fold. decreas |
Function
Pathways and Gene Ontology
Reactome pathways
1 pathways
| ID | Pathway |
|---|---|
| R-HSA-209905 | Catecholamine biosynthesis |
MSigDB gene sets: 117 (showing top):
GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GCM_RING1, GCM_FCGR2B, MORF_PML, MORF_PDPK1, GOBP_METHYLATION, MORF_MT4, GCM_BECN1, KEGG_TYROSINE_METABOLISM, WANG_HCP_PROSTATE_CANCER, MORF_ORC1L, MORF_MYST2, MORF_RBM8A
GO Biological Process (3): methylation (GO:0032259), epinephrine biosynthetic process (GO:0042418), catecholamine biosynthetic process (GO:0042423)
GO Molecular Function (5): phenylethanolamine N-methyltransferase activity (GO:0004603), protein binding (GO:0005515), methyltransferase activity (GO:0008168), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740)
GO Cellular Component (1): cytosol (GO:0005829)
Reactome top-level categories
Rollup of top-1 pathways:
| Category | Pathways |
|---|---|
| Metabolism of amine-derived hormones | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| metabolic process | 1 |
| epinephrine metabolic process | 1 |
| catecholamine biosynthetic process | 1 |
| catecholamine metabolic process | 1 |
| catechol-containing compound biosynthetic process | 1 |
| biogenic amine biosynthetic process | 1 |
| N-methyltransferase activity | 1 |
| S-adenosylmethionine-dependent methyltransferase activity | 1 |
| binding | 1 |
| transferase activity, transferring one-carbon groups | 1 |
| methyltransferase activity | 1 |
| catalytic activity | 1 |
| cytoplasm | 1 |
| cellular anatomical structure | 1 |
Protein interactions and networks
STRING
536 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| PNMT | TH | P07101 | 948 |
| PNMT | DBH | P09172 | 901 |
| PNMT | DDC | P20711 | 732 |
| PNMT | CRH | P06850 | 720 |
| PNMT | PENK | P01210 | 685 |
| PNMT | PAH | P00439 | 679 |
| PNMT | COMT | P21964 | 670 |
| PNMT | POMC | P01189 | 666 |
| PNMT | AOC1 | P19801 | 666 |
| PNMT | TOMT | Q8WZ04 | 638 |
| PNMT | CHGB | P05060 | 609 |
| PNMT | MAOA | P21397 | 591 |
| PNMT | MAOB | P27338 | 591 |
| PNMT | NPY | P01303 | 583 |
| PNMT | SDHD | O14521 | 529 |
IntAct
10 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| PNMT | LNX1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| PNMT | KLHL8 | psi-mi:“MI:0915”(physical association) | 0.560 |
| ESR1 | PGK2 | psi-mi:“MI:0914”(association) | 0.530 |
| PNMT | TERF1 | psi-mi:“MI:0915”(physical association) | 0.370 |
| PNMT | TERF2IP | psi-mi:“MI:0915”(physical association) | 0.370 |
| PNMT | KLHL8 | psi-mi:“MI:0915”(physical association) | 0.000 |
| PNMT | LNX1 | psi-mi:“MI:0915”(physical association) | 0.000 |
BioGRID (13): PNMT (Affinity Capture-MS), PNMT (Negative Genetic), PNMT (Positive Genetic), PNMT (Positive Genetic), RPS6KA4 (Positive Genetic), PNMT (Positive Genetic), UCK2 (Positive Genetic), RELA (Positive Genetic), PNMT (Two-hybrid), KLHL8 (Two-hybrid), PNMT (Affinity Capture-MS), PNMT (Two-hybrid), PNMT (Two-hybrid)
ESM2 similar proteins: A0A5F8AH41, A0AVI4, A0JMH2, A1Y9I9, A5WVX1, B0X4N1, B4P925, D3ZX08, O55171, O88512, O95050, O97972, P0DPD7, P0DPE0, P0DPE1, P10937, P10938, P11086, P40935, P40936, Q06AU9, Q08DK0, Q14CH7, Q32PE2, Q32Q92, Q3SZG9, Q3URQ7, Q568P9, Q5E9L5, Q5JTZ9, Q5RCH4, Q5RFR7, Q6NTR1, Q6NZB1, Q7QIL2, Q7TMC8, Q80YU0, Q8HY87, Q8K304, Q8NFF5
Diamond homologs: A0A5F8AH41, O55239, O95050, O97972, P10937, P10938, P11086, P40261, P40935, P40936, Q06AU9, Q06AV1, Q5RFR7
SIGNOR signaling
2 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| PNMT | “up-regulates quantity” | adrenaline | “chemical modification” |
| PNMT | “down-regulates quantity” | noradrenaline | “chemical modification” |
Disease & clinical
Clinical variants and AI predictions
ClinVar
56 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 48 |
| Likely benign | 4 |
| Benign | 2 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
386 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 17:39669617:T:A | acceptor_gain | 1.0000 |
| 17:39669625:CCA:C | acceptor_loss | 1.0000 |
| 17:39669626:CAGG:C | acceptor_loss | 1.0000 |
| 17:39669627:A:AG | acceptor_gain | 1.0000 |
| 17:39669627:A:G | acceptor_loss | 1.0000 |
| 17:39669628:G:GC | acceptor_gain | 1.0000 |
| 17:39669628:GGT:G | acceptor_gain | 1.0000 |
| 17:39669772:G:GT | donor_gain | 1.0000 |
| 17:39669831:C:T | donor_gain | 1.0000 |
| 17:39669834:GGG:G | donor_gain | 1.0000 |
| 17:39669835:GG:G | donor_gain | 1.0000 |
| 17:39669835:GGG:G | donor_gain | 1.0000 |
| 17:39669835:GGGTA:G | donor_loss | 1.0000 |
| 17:39669836:GG:G | donor_gain | 1.0000 |
| 17:39669837:G:GA | donor_loss | 1.0000 |
| 17:39669837:G:GG | donor_gain | 1.0000 |
| 17:39669838:T:G | donor_loss | 1.0000 |
| 17:39669947:ACAG:A | acceptor_gain | 1.0000 |
| 17:39669947:ACAGG:A | acceptor_gain | 1.0000 |
| 17:39668676:CGG:C | donor_loss | 0.9900 |
| 17:39668678:G:C | donor_loss | 0.9900 |
| 17:39668679:T:G | donor_loss | 0.9900 |
| 17:39669622:T:A | acceptor_gain | 0.9900 |
| 17:39669627:AG:A | acceptor_gain | 0.9900 |
| 17:39669627:AGGT:A | acceptor_gain | 0.9900 |
| 17:39669628:GG:G | acceptor_gain | 0.9900 |
| 17:39669628:GGTG:G | acceptor_gain | 0.9900 |
| 17:39669628:GGTGA:G | acceptor_gain | 0.9900 |
| 17:39669736:G:GT | donor_gain | 0.9900 |
| 17:39669797:GCAT:G | donor_gain | 0.9900 |
AlphaMissense
1820 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 17:39670102:A:C | S188R | 0.994 |
| 17:39670104:C:A | S188R | 0.994 |
| 17:39670104:C:G | S188R | 0.994 |
| 17:39668563:T:C | F30L | 0.992 |
| 17:39668565:C:A | F30L | 0.992 |
| 17:39668565:C:G | F30L | 0.992 |
| 17:39670084:T:C | F182L | 0.983 |
| 17:39670086:C:A | F182L | 0.983 |
| 17:39670086:C:G | F182L | 0.983 |
| 17:39669793:T:A | W123R | 0.982 |
| 17:39669793:T:C | W123R | 0.982 |
| 17:39669706:T:C | F94L | 0.981 |
| 17:39669708:T:A | F94L | 0.981 |
| 17:39669708:T:G | F94L | 0.981 |
| 17:39669725:C:A | T100K | 0.980 |
| 17:39670089:C:G | C183W | 0.980 |
| 17:39669744:C:A | N106K | 0.978 |
| 17:39669744:C:G | N106K | 0.978 |
| 17:39669728:A:T | D101V | 0.975 |
| 17:39668564:T:C | F30S | 0.974 |
| 17:39668564:T:G | F30C | 0.974 |
| 17:39668641:T:A | W56R | 0.974 |
| 17:39668641:T:C | W56R | 0.974 |
| 17:39668643:G:C | W56C | 0.974 |
| 17:39668643:G:T | W56C | 0.974 |
| 17:39669691:A:C | S89R | 0.974 |
| 17:39669693:T:A | S89R | 0.974 |
| 17:39669693:T:G | S89R | 0.974 |
| 17:39669763:T:A | W113R | 0.974 |
| 17:39669763:T:C | W113R | 0.974 |
dbSNP variants (sampled 300 via entrez): RS1000060686 (17:39669165 C>T), RS1000303052 (17:39666412 C>T), RS1000681701 (17:39667490 G>C), RS1001040040 (17:39670577 A>C,G), RS1002355862 (17:39668602 C>T), RS1002463115 (17:39667464 C>G,T), RS1002976726 (17:39667353 G>A), RS1004599803 (17:39667307 G>A), RS1004717498 (17:39668390 C>A,G,T), RS1005548956 (17:39668492 G>A), RS1006562326 (17:39670027 C>G,T), RS1006732991 (17:39670723 G>C), RS1007111530 (17:39666989 A>AC), RS1007451551 (17:39668340 A>G,T), RS1007547213 (17:39670653 G>A)
Disease associations
OMIM: gene MIM:171190 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
13 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST000624_15 | Ulcerative colitis | 3.000000e-08 |
| GCST000964_1 | Ulcerative colitis | 5.000000e-11 |
| GCST003119_9 | Urinary metabolites | 4.000000e-26 |
| GCST003589_1 | Bronchial hyperresponsiveness in asthma | 3.000000e-20 |
| GCST007235_3 | Pancreatic ductal adenocarcinoma | 1.000000e-06 |
| GCST007564_21 | Asthma or allergic disease (pleiotropy) | 4.000000e-17 |
| GCST008757_30 | Alcohol consumption | 1.000000e-09 |
| GCST008916_10 | Asthma | 5.000000e-09 |
| GCST008916_21 | Asthma | 2.000000e-62 |
| GCST008916_45 | Asthma | 3.000000e-10 |
| GCST008916_86 | Asthma | 2.000000e-14 |
| GCST009798_16 | Asthma | 8.000000e-27 |
| GCST010002_123 | Refractive error | 1.000000e-24 |
EFO canonical traits (1, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0005116 | urinary metabolite measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL4617 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,522 (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 |
|---|---|---|---|
| CHEMBL1088977 | ADEMETIONINE | 3 | 1,522 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB variants
3 variants.
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs876493 | PNMT | 0.00 | 0 | ||
| rs2934965 | PNMT | 0.00 | 0 | ||
| rs2941523 | PNMT | 0.00 | 0 |
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — Catecholamine turnover
Most potent curated ligand interactions (1 total), top 1:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| LY134046 | Inhibition | 7.6 | pKi |
Binding affinities (BindingDB)
26 measured of 26 human assays (28 total across all organisms); most potent 26 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value |
|---|---|---|
| 3-(hydroxymethyl)-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | KI | 23 nM |
| 3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | KI | 52 nM |
| N-(4-chlorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | KI | 63 nM |
| 3-(fluoromethyl)-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | KI | 130 nM |
| 3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | KI | 150 nM |
| 3-(fluoromethyl)-N-(3,3,3-trifluoropropyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | KI | 220 nM |
| N-(4-chlorophenyl)-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | KI | 270 nM |
| 7-methanesulfonyl-1,2,3,4-tetrahydroisoquinoline | KI | 790 nM |
| 3-(fluoromethyl)-7-methanesulfonyl-1,2,3,4-tetrahydroisoquinoline | KI | 1100 nM |
| ((+/-)-3-Fluoromethyl-7-(3,3,3-trifluoropropylsulfonyl)-1,2,3,4-tetrahydroisoquinoline | KI | 1300 nM |
| N-ethyl-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | KI | 1400 nM |
| 3-(fluoromethyl)-7-[(2,2,2-trifluoroethane)sulfonyl]-1,2,3,4-tetrahydroisoquinoline | KI | 1400 nM |
| 3-(fluoromethyl)-N-propyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | KI | 1700 nM |
| 3-(fluoromethyl)-7-(propane-1-sulfonyl)-1,2,3,4-tetrahydroisoquinoline | KI | 2400 nM |
| 3-(fluoromethyl)-N-methyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | KI | 3700 nM |
| 3-(fluoromethyl)-N-(2-methoxyethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | KI | 5100 nM |
| 7-(trichloromethane)sulfonyl-1,2,3,4-tetrahydroisoquinoline | KI | 6300 nM |
| 7-(prop-2-ene-1-sulfonyl)-1,2,3,4-tetrahydroisoquinoline | KI | 9000 nM |
| ((+/-)-7-Ethylsulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline | KI | 14000 nM |
| 7-(butane-1-sulfonyl)-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline | KI | 18000 nM |
| 7-(benzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline | KI | 23000 nM |
| 7-{[(4-chlorophenyl)methane]sulfonyl}-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline | KI | 32000 nM |
| ((+/-)-3-Fluoromethyl-7-(4,4,4-trifluorobutylsulfonyl)-1,2,3,4-tetrahydroisoquinoline | KI | 67000 nM |
| 3-(fluoromethyl)-7-[(3-methoxypropane)sulfonyl]-1,2,3,4-tetrahydroisoquinoline | KI | 72000 nM |
| 3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinoline-7-sulfonic acid adamantan-1-ylamide | KI | 88000 nM |
| 1,2,3,4-tetrahydroisoquinoline | KI | 4.7e+07 nM |
ChEMBL bioactivities
250 potent at pChembl≥5 of 305 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
PubChem BioAssay actives
193 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 |
|---|---|---|---|---|
| N-(4-chlorophenyl)-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 298194: Inhibition of human PNMT K57A mutant | ki | 0.0010 | uM |
| N-(4-chlorophenyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 298194: Inhibition of human PNMT K57A mutant | ki | 0.0013 | uM |
| N-(4-chlorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 298194: Inhibition of human PNMT K57A mutant | ki | 0.0014 | uM |
| 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline | 282848: Binding affinity to human wild type his-tagged PNMT | ki | 0.0015 | uM |
| 4-[[3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]sulfonyl]thiomorpholine | 298194: Inhibition of human PNMT K57A mutant | ki | 0.0018 | uM |
| (2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-[3-(1,2,3,4-tetrahydroisoquinolin-3-ylmethylamino)propylsulfanylmethyl]oxolane-3,4-diol | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0021 | uM |
| 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline;hydrochloride | 155332: Binding affinity for phenylethanolamine N-methyl-transferase was determined. | ki | 0.0030 | uM |
| (2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-[2-[(7-chloro-1,2,3,4-tetrahydroisoquinolin-3-yl)methylamino]ethylsulfanylmethyl]oxolane-3,4-diol | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0032 | uM |
| (2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-[3-[(7-chloro-1,2,3,4-tetrahydroisoquinolin-3-yl)methylamino]propylsulfanylmethyl]oxolane-3,4-diol | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0033 | uM |
| (2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-[3-[(7-nitro-1,2,3,4-tetrahydroisoquinolin-3-yl)methylamino]propylsulfanylmethyl]oxolane-3,4-diol | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0035 | uM |
| (2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-[2-[(7-nitro-1,2,3,4-tetrahydroisoquinolin-3-yl)methylamino]ethylsulfanylmethyl]oxolane-3,4-diol | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0038 | uM |
| (2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-[4-(1,2,3,4-tetrahydroisoquinolin-3-ylmethylamino)butylsulfanylmethyl]oxolane-3,4-diol | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0039 | uM |
| [(3R)-7-bromo-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol | 239072: Inhibitory binding affinity for phenylethanolamine N-methyl-transferase (PNMT) | ki | 0.0049 | uM |
| 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine | 239072: Inhibitory binding affinity for phenylethanolamine N-methyl-transferase (PNMT) | ki | 0.0100 | uM |
| (3S)-3-methyl-7-nitro-1,2,3,4-tetrahydroisoquinoline | 313557: Inhibition of human PNMT by radiochemical assay | ki | 0.0160 | uM |
| 3-(fluoromethyl)-N-(3,3,3-trifluoropropyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 298194: Inhibition of human PNMT K57A mutant | ki | 0.0170 | uM |
| (2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-[6-(1,2,3,4-tetrahydroisoquinolin-3-ylmethylamino)hexylsulfanylmethyl]oxolane-3,4-diol | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0180 | uM |
| 6,7,8-trichloro-1,2,3,4-tetrahydroisoquinoline | 155335: Dissociation constant(Ki) of compound was determined to measure Phenylethanolamine N-methyl-transferase inhibitory potency | ki | 0.0200 | uM |
| 3-(hydroxymethyl)-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 1796978: Radiochemical Assay of PNMT Inhibitors from Article 10.1021/jm060466d: “Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamine N-methyltransferase.” | ki | 0.0230 | uM |
| 3-(hydroxymethyl)-N-(3,3,3-trifluoropropyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 239080: In vitro binding affinity against human phenylethanolamine N-Methyltransferase | ki | 0.0280 | uM |
| 7-chloro-1,2,3,4-tetrahydroisoquinoline | 155334: Dissociation constant(Ki) of compound was determined to measure PNMT-inhibitory potency | ki | 0.0290 | uM |
| 8-chloro-1,2,3,4-tetrahydroisoquinoline | 155333: Dissociation constant(Ki) of compound was determined to measure PNMT-inhibitory potency | ki | 0.0300 | uM |
| (2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-[2-(1,2,3,4-tetrahydroisoquinolin-3-ylmethylamino)ethylsulfanylmethyl]oxolane-3,4-diol | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0380 | uM |
| N-[3-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]propyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0460 | uM |
| 3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 1796978: Radiochemical Assay of PNMT Inhibitors from Article 10.1021/jm060466d: “Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamine N-methyltransferase.” | ki | 0.0520 | uM |
| 5,6,7,8-tetrachloro-1,2,3,4-tetrahydroisoquinoline | 155335: Dissociation constant(Ki) of compound was determined to measure Phenylethanolamine N-methyl-transferase inhibitory potency | ki | 0.0520 | uM |
| 7-bromo-1,2,3,4-tetrahydroisoquinoline | 293029: Binding affinity to human PNMT | ki | 0.0560 | uM |
| (2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-[5-(1,2,3,4-tetrahydroisoquinolin-3-ylmethylamino)pentylsulfanylmethyl]oxolane-3,4-diol | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0570 | uM |
| 5,7,8-trichloro-1,2,3,4-tetrahydroisoquinoline | 155334: Dissociation constant(Ki) of compound was determined to measure PNMT-inhibitory potency | ki | 0.0590 | uM |
| (3R)-3-(fluoromethyl)-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 239480: In vitro binding affinity against recombinant human Phenylethanolamine N-methyl-transferase expressed in Escherichia coli using [methyl-3H]-AdoMet | ki | 0.0610 | uM |
| 3-(difluoromethyl)-7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline | 264506: Binding affinity to human PNMT | ki | 0.0670 | uM |
| 3-(fluoromethyl)-7-iodo-1,2,3,4-tetrahydroisoquinoline | 239072: Inhibitory binding affinity for phenylethanolamine N-methyl-transferase (PNMT) | ki | 0.0700 | uM |
| N-[3-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]propyl]-7-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxamide | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0700 | uM |
| N-[2-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]ethyl]-7-chloro-1,2,3,4-tetrahydroisoquinoline-3-carboxamide | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0710 | uM |
| (3R)-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 239480: In vitro binding affinity against recombinant human Phenylethanolamine N-methyl-transferase expressed in Escherichia coli using [methyl-3H]-AdoMet | ki | 0.0720 | uM |
| 3-methyl-7-nitro-1,2,3,4-tetrahydroisoquinoline | 257555: Inhibitory activity against human PNMT | ki | 0.0720 | uM |
| N-[2-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]ethyl]-7-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxamide | 1700192: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis | ki | 0.0860 | uM |
| 1-(2,3-dichlorophenyl)ethanamine | 239072: Inhibitory binding affinity for phenylethanolamine N-methyl-transferase (PNMT) | ki | 0.0900 | uM |
| 7-bromo-3-(difluoromethyl)-1,2,3,4-tetrahydroisoquinoline | 264506: Binding affinity to human PNMT | ki | 0.0940 | uM |
| (3R)-3-(fluoromethyl)-N-(3,3,3-trifluoropropyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 239480: In vitro binding affinity against recombinant human Phenylethanolamine N-methyl-transferase expressed in Escherichia coli using [methyl-3H]-AdoMet | ki | 0.0990 | uM |
| 7,8-dichloro-2-[4-(7,8-dichloro-3,4-dihydro-1H-isoquinolin-2-yl)butyl]-3,4-dihydro-1H-isoquinoline;dihydrochloride | 155323: Inhibition of rabbit adrenal phenylethanolamine N-methyl-transferase | ic50 | 0.1000 | uM |
| (3R)-N-(4-chlorophenyl)-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 239480: In vitro binding affinity against recombinant human Phenylethanolamine N-methyl-transferase expressed in Escherichia coli using [methyl-3H]-AdoMet | ki | 0.1100 | uM |
| 3-(fluoromethyl)-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 1796978: Radiochemical Assay of PNMT Inhibitors from Article 10.1021/jm060466d: “Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamine N-methyltransferase.” | ki | 0.1300 | uM |
| 3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 1796978: Radiochemical Assay of PNMT Inhibitors from Article 10.1021/jm060466d: “Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamine N-methyltransferase.” | ki | 0.1500 | uM |
| N-ethyl-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 239080: In vitro binding affinity against human phenylethanolamine N-Methyltransferase | ki | 0.1700 | uM |
| 3-(difluoromethyl)-7-nitro-1,2,3,4-tetrahydroisoquinoline | 264506: Binding affinity to human PNMT | ki | 0.1700 | uM |
| 3-(hydroxymethyl)-N-propyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide | 239080: In vitro binding affinity against human phenylethanolamine N-Methyltransferase | ki | 0.1900 | uM |
| 3-(difluoromethyl)-7-iodo-1,2,3,4-tetrahydroisoquinoline | 264506: Binding affinity to human PNMT | ki | 0.2000 | uM |
| 7-bromo-1,2,3,4-tetrahydrobenzo[h]isoquinoline | 293029: Binding affinity to human PNMT | ki | 0.2200 | uM |
| (7-thiomorpholin-4-ylsulfonyl-1,2,3,4-tetrahydroisoquinolin-3-yl)methanol | 239080: In vitro binding affinity against human phenylethanolamine N-Methyltransferase | ki | 0.2300 | uM |
CTD chemical–gene interactions
12 total (human), top 12 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Benzo(a)pyrene | decreases expression, increases methylation | 2 |
| MT19c compound | decreases expression | 1 |
| Bortezomib | decreases expression | 1 |
| Panobinostat | affects cotreatment, affects expression | 1 |
| Cisplatin | affects cotreatment, affects expression | 1 |
| Dexamethasone | increases expression | 1 |
| Formaldehyde | decreases expression | 1 |
| Nicotine | increases expression | 1 |
| Phenobarbital | decreases expression | 1 |
| Tretinoin | decreases expression | 1 |
| Triclosan | decreases expression | 1 |
| Valproic Acid | increases methylation | 1 |
ChEMBL screening assays
72 unique, capped per target: 65 binding, 5 functional, 2 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1024773 | Binding | Binding affinity to wild type human PNMT by liquid scintillation spectrometry in presence of [3H]AdoMet | Time-dependent inactivation of human phenylethanolamine N-methyltransferase by 7-isothiocyanatotetrahydroisoquinoline. — Bioorg Med Chem Lett |
| CHEMBL4416337 | ADMET | Inhibition of human PNMT expressed in Escherichia coli at 10 uM assessed as reduction in SAH level using DL-normetanephrine as substrate in presence of SAM incubated for 45 mins by LC-MS/MS analysis relative to control | High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT). — J Med Chem |
| CHEMBL759758 | Functional | Ability to inhibit rabbit adrenal phenylethanolamine N-methyl-transferase norepinephrine to epinephrine (E13), in vitro, at 10 e-4 M compound concentration. | Tetrahydrothiadiazoloisoquinolines: synthesis and inhibition of phenylethanolamine-N-methyltransferase. — J Med Chem |
Cellosaurus cell lines
3 cell lines: 3 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_D1PW | Abcam K-562 PNMT KO | Cancer cell line | Female |
| CVCL_D2LI | Abcam Raji PNMT KO | Cancer cell line | Male |
| CVCL_WQ33 | Abcam Jurkat PNMT KO | Cancer cell line | Male |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.