NOTUM

gene

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Summary

NOTUM (notum, palmitoleoyl-protein carboxylesterase, HGNC:27106) is a protein-coding gene on chromosome 17q25.3, encoding Palmitoleoyl-protein carboxylesterase NOTUM (Q6P988). Carboxylesterase that acts as a key negative regulator of the Wnt signaling pathway by specifically mediating depalmitoleoylation of WNT proteins.

Enables palmitoleyl hydrolase activity. Involved in negative regulation of Wnt signaling pathway and protein depalmitoleylation. Acts upstream of or within bone development and regulation of bone mineralization. Predicted to be located in endoplasmic reticulum lumen and extracellular region.

Source: NCBI Gene 147111 — RefSeq curated summary.

At a glance

GWAS associations: 3
Clinical variants (ClinVar): 93 total
Druggable target: yes — 2 molecules with ChEMBL bioactivity
MANE Select transcript: NM_178493

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27106
Approved symbol	NOTUM
Name	notum, palmitoleoyl-protein carboxylesterase
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185269
Ensembl biotype	protein_coding
OMIM	609847
Entrez	147111

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000409678, ENST00000425009, ENST00000477214, ENST00000489218, ENST00000883520, ENST00000959245, ENST00000959246, ENST00000959247

RefSeq mRNA: 1 — MANE Select: NM_178493 NM_178493

CCDS: CCDS32771

Canonical transcript exons

ENST00000409678 — 11 exons

Exon	Start	End
ENSE00001301311	81955397	81955544
ENSE00001329763	81954256	81954303
ENSE00001907310	81960587	81961187
ENSE00001909070	81952507	81953267
ENSE00002761718	81958335	81958393
ENSE00002775563	81958935	81958995
ENSE00002785826	81956650	81956750
ENSE00002969586	81957806	81957908
ENSE00003464762	81959640	81959692
ENSE00003512097	81959471	81959566
ENSE00003784553	81956883	81957074

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 99.04.

FANTOM5 (CAGE): breadth broad, TPM avg 10.0375 / max 1667.6849, expressed in 357 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168880	6.7256	178
168882	1.2353	92
168879	0.7495	95
168877	0.4065	155
208459	0.3044	81
168881	0.2545	69
208460	0.1258	78
168883	0.1077	33
168878	0.0778	34
168876	0.0506	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	99.04	gold quality
kidney epithelium	UBERON:0004819	91.52	gold quality
placenta	UBERON:0001987	91.28	gold quality
left ventricle myocardium	UBERON:0006566	86.39	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.07	gold quality
myocardium	UBERON:0002349	84.80	gold quality
vena cava	UBERON:0004087	84.68	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	82.45	gold quality
parotid gland	UBERON:0001831	81.55	gold quality
biceps brachii	UBERON:0001507	80.96	gold quality
epithelial cell of pancreas	CL:0000083	80.84	gold quality
cerebellar vermis	UBERON:0004720	79.64	gold quality
sperm	CL:0000019	79.62	gold quality
body of tongue	UBERON:0011876	79.08	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	78.50	silver quality
hindlimb stylopod muscle	UBERON:0004252	78.13	gold quality
pylorus	UBERON:0001166	78.12	silver quality
skeletal muscle tissue	UBERON:0001134	78.11	gold quality
oocyte	CL:0000023	77.91	silver quality
substantia nigra pars reticulata	UBERON:0001966	77.78	silver quality
tongue	UBERON:0001723	77.36	gold quality
thymus	UBERON:0002370	77.26	silver quality
right lobe of liver	UBERON:0001114	77.10	gold quality
layer of synovial tissue	UBERON:0007616	76.99	gold quality
nipple	UBERON:0002030	76.96	silver quality
pharyngeal mucosa	UBERON:0000355	76.90	silver quality
liver	UBERON:0002107	76.86	gold quality
substantia nigra pars compacta	UBERON:0001965	76.83	silver quality
pericardium	UBERON:0002407	76.74	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.57	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	8437.14
E-HCAD-23	yes	2120.08
E-MTAB-6678	yes	18.16
E-ANND-3	no	1.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, TCF4, TCF7L2

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 13)

Overexpression of NOTUM is associated with hepatocellular carcinoma (PMID:18429952)
Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase (PMID:25731175)
Data show that notum and glypican-1 and glypican-3 gene expression during colorectal cancer (CRC) development and present evidence to suggest them as potential new biomarkers of CRC pathogenesis. (PMID:26517809)
NOTUM expression was increased in metastatic cells. Proliferation was suppressed by inhibiting expression of NOTUM. Knockdown of NOTUM genes inhibited proliferation as well as migration, with possible involvement of p38 and c-JUN N-terminal kinase in this process. (PMID:30343282)
results reveal a role of the stem cell niche in ageing and demonstrate that targeting of Notum can promote regeneration of aged tissues (PMID:31292548)
Therapies targeting osteoblast-derived NOTUM may prevent nonvertebral fractures. (PMID:31307226)
Structural characterization of melatonin as an inhibitor of the Wnt deacylase Notum. (PMID:31876313)
Notum deacylates octanoylated ghrelin. (PMID:33647468)
NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. (PMID:34079124)
Notum palmitoleoyl-protein carboxylesterase regulates Fas cell surface death receptor-mediated apoptosis via the Wnt signaling pathway in colon adenocarcinoma. (PMID:34402722)
Notum leads to potential pro-survival of OSCC through crosstalk between Shh and Wnt/beta-catenin signaling via p-GSK3beta. (PMID:36280040)
Notum enhances gastric cancer stem-like cell properties through upregulation of Sox2 by PI3K/AKT signaling pathway. (PMID:37749430)
NOTUM plays a bidirectionally modulatory role in the odontoblastic differentiation of human stem cells from the apical papilla through the WNT/beta-catenin signaling pathway. (PMID:38278124)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	notum1a	ENSDARG00000031126
danio_rerio	notum1b	ENSDARG00000117145
mus_musculus	Notum	ENSMUSG00000042988
rattus_norvegicus	Notum	ENSRNOG00000036680

Protein

Protein identifiers

Palmitoleoyl-protein carboxylesterase NOTUM — Q6P988 (reviewed: Q6P988)

Alternative names: hNOTUM

All UniProt accessions (3): C9JYG8, K7EIG3, Q6P988

UniProt curated annotations — full annotation on UniProt →

Function. Carboxylesterase that acts as a key negative regulator of the Wnt signaling pathway by specifically mediating depalmitoleoylation of WNT proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors.

Subcellular location. Secreted.

Tissue specificity. Rarely expressed in adult normal tissues.

Induction. Up-regulated in hepatocellular carcinoma (HCC) with high intracellular beta-catenin.

Similarity. Belongs to the pectinacetylesterase family. Notum subfamily.

RefSeq proteins (1): NP_848588* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004963	PAE/NOTUM	Family

Pfam: PF03283

Enzyme classification (BRENDA):

EC 3.1.1.98 — [Wnt protein] O-palmitoleoyl-L-serine hydrolase (BRENDA: 5 organisms, 6 substrates, 470 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

[Wnt protein]-O-(9Z)-hexadecenoyl-L-serine + H2O = [Wnt protein]-L-serine + (9Z)-hexadecenoate + H(+) (RHEA:45340)

UniProt features (53 total): strand 20, helix 15, turn 7, active site 3, sequence conflict 2, signal peptide 1, chain 1, region of interest 1, modified residue 1, glycosylation site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

141 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7BNB	X-RAY DIFFRACTION	1.16
7BLS	X-RAY DIFFRACTION	1.19
7BLT	X-RAY DIFFRACTION	1.2
6YSK	X-RAY DIFFRACTION	1.21
7BLU	X-RAY DIFFRACTION	1.21
7BO2	X-RAY DIFFRACTION	1.21
7B2Y	X-RAY DIFFRACTION	1.23
7B8A	X-RAY DIFFRACTION	1.23
7BNL	X-RAY DIFFRACTION	1.23
6TUZ	X-RAY DIFFRACTION	1.24
7ARG	X-RAY DIFFRACTION	1.24
7B2V	X-RAY DIFFRACTION	1.24
7B2Z	X-RAY DIFFRACTION	1.24
7B4X	X-RAY DIFFRACTION	1.24
6R8R	X-RAY DIFFRACTION	1.27
7B3G	X-RAY DIFFRACTION	1.28
7B3H	X-RAY DIFFRACTION	1.28
7B3P	X-RAY DIFFRACTION	1.28
8BT8	X-RAY DIFFRACTION	1.28
6ZVL	X-RAY DIFFRACTION	1.3
8BTH	X-RAY DIFFRACTION	1.3
8BTI	X-RAY DIFFRACTION	1.31
7BDC	X-RAY DIFFRACTION	1.32
7B50	X-RAY DIFFRACTION	1.33
6YXI	X-RAY DIFFRACTION	1.34
7B37	X-RAY DIFFRACTION	1.34
7B3I	X-RAY DIFFRACTION	1.34
7B3X	X-RAY DIFFRACTION	1.34
7B9I	X-RAY DIFFRACTION	1.34
8BTA	X-RAY DIFFRACTION	1.34

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P988-F1	84.47	0.66

Functional residue map

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

Catalytic / active sites (3): 232 (charge relay system); 340 (charge relay system); 389 (charge relay system)

Post-translational modifications (1): 81

Glycosylation sites (1): 96

Mutagenesis-validated functional residues (1):

Position	Phenotype
232	abolishes enzyme activity. unable to mediate serine depalmitoleoylation of wnt proteins.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-5362798	Release of Hh-Np from the secreting cell
R-HSA-8957275	Post-translational protein phosphorylation

MSigDB gene sets: 126 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_MACROMOLECULE_DEACYLATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, NFKB_C, GOBP_BONE_DEVELOPMENT, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_BONE_MINERALIZATION, GOBP_OSSIFICATION, GTGACTT_MIR224, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOBP_NEGATIVE_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (6): Wnt signaling pathway (GO:0016055), negative regulation of Wnt signaling pathway (GO:0030178), regulation of bone mineralization (GO:0030500), bone development (GO:0060348), negative regulation of canonical Wnt signaling pathway (GO:0090090), protein depalmitoleylation (GO:1990697)

GO Molecular Function (7): C-type glycerophospholipase activity (GO:0004629), protein-containing complex destabilizing activity (GO:0140776), palmitoleyl hydrolase activity (GO:1990699), protein binding (GO:0005515), lipase activity (GO:0016298), hydrolase activity (GO:0016787), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (2): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of proteins	1
Hedgehog ligand biogenesis	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hydrolase activity, acting on ester bonds	2
cell surface receptor signaling pathway	1
negative regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
regulation of ossification	1
bone mineralization	1
regulation of biomineral tissue development	1
skeletal system development	1
animal organ development	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
protein deacylation	1
lipoprotein catabolic process	1
glycerophospholipase activity	1
phosphoric diester hydrolase activity	1
molecular_function	1
carboxylic ester hydrolase activity	1
binding	1
catalytic activity	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOTUM	WNT1	P04628	778
NOTUM	GPC1	P35052	773
NOTUM	AXIN2	Q9Y2T1	600
NOTUM	GPC6	Q9Y625	562
NOTUM	NKD1	Q969G9	558
NOTUM	APCDD1	Q8J025	548
NOTUM	ZNRF3	Q9ULT6	532
NOTUM	RNF43	Q68DV7	530
NOTUM	WIF1	Q9Y5W5	529
NOTUM	PORCN	Q9H237	514
NOTUM	SFRP1	Q8N474	486
NOTUM	WLS	Q5T9L3	482
NOTUM	GPC3	P51654	482
NOTUM	AXIN1	O15169	473
NOTUM	GPC4	O75487	460

IntAct

9 interactions, top by confidence:

A	B	Type	Score
NOTUM	ZNF655	psi-mi:“MI:0915”(physical association)	0.560
NOTUM	GPC3	psi-mi:“MI:0407”(direct interaction)	0.440
NOTUM	WNT3A	psi-mi:“MI:0197”(deacetylation reaction)	0.440
NOTUM	NOTUM	psi-mi:“MI:0407”(direct interaction)	0.440
NOTUM	Wnt3a	psi-mi:“MI:0197”(deacetylation reaction)	0.440
NOTUM	WNT7A	psi-mi:“MI:0407”(direct interaction)	0.440
NOTUM	ZNF655	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): ZNF655 (Two-hybrid), NOTUM (Proximity Label-MS), NOTUM (Proximity Label-MS), NOTUM (Proximity Label-MS)

ESM2 similar proteins: A0A0D3QS98, A0A0D3QS99, A4D0V7, C5H5C4, F6Q1T7, O70309, O75354, P17405, P18084, P18424, P22413, P50747, P52850, P58242, P61642, P80747, Q04519, Q0VBD0, Q0VD19, Q13219, Q52KP5, Q58CQ9, Q5QQ51, Q5STE3, Q64687, Q6DFZ6, Q6KFX9, Q6MZW2, Q6P988, Q6UWX4, Q6YGZ1, Q6ZXD2, Q71RP1, Q812F8, Q8BJQ9, Q8C1F4, Q8C419, Q8N5D6, Q8N6G5, Q8R116

Diamond homologs: A0A0D3QS97, A0A0D3QS98, A0A0D3QS99, C5H5C4, E7F0Z8, F4I839, F8U830, Q66GM8, Q6DFZ6, Q6P988, Q8R116, Q9SFF6, Q9VUX3, O80731, Q84JS1, B9DFR3, F4I107, Q6DBP4, Q940J8, Q9FH82, Q9SR22, Q9SR23

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1628 predictions. Top by Δscore:

Variant	Effect	Δscore
17:81953268:C:CC	acceptor_gain	1.0000
17:81955388:CACA:C	donor_gain	1.0000
17:81955391:A:AC	donor_gain	1.0000
17:81955392:C:CC	donor_gain	1.0000
17:81955395:A:AC	donor_gain	1.0000
17:81955395:ACGG:A	donor_gain	1.0000
17:81955396:C:CA	donor_gain	1.0000
17:81955396:CGG:C	donor_gain	1.0000
17:81955396:CGGC:C	donor_gain	1.0000
17:81955396:CGGCA:C	donor_gain	1.0000
17:81955400:ACGT:A	donor_gain	1.0000
17:81955401:CGTC:C	donor_gain	1.0000
17:81955403:T:TA	donor_gain	1.0000
17:81955404:C:A	donor_gain	1.0000
17:81955545:C:CC	acceptor_gain	1.0000
17:81956648:A:AC	donor_gain	1.0000
17:81956649:C:CC	donor_gain	1.0000
17:81956649:CAG:C	donor_gain	1.0000
17:81956649:CAGCG:C	donor_gain	1.0000
17:81956747:GTACC:G	acceptor_loss	1.0000
17:81956749:ACCT:A	acceptor_loss	1.0000
17:81956750:CCTGG:C	acceptor_loss	1.0000
17:81956751:CTGGA:C	acceptor_loss	1.0000
17:81956879:GCAC:G	donor_loss	1.0000
17:81956880:CA:C	donor_loss	1.0000
17:81956881:A:AG	donor_loss	1.0000
17:81956882:CCT:C	donor_loss	1.0000
17:81956904:T:TA	donor_gain	1.0000
17:81957070:CCGCG:C	acceptor_gain	1.0000
17:81957071:CGCG:C	acceptor_gain	1.0000

AlphaMissense

3234 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:81953210:C:A	W414C	0.999
17:81953210:C:G	W414C	0.999
17:81953261:C:A	W397C	0.999
17:81953261:C:G	W397C	0.999
17:81957061:C:A	G237W	0.999
17:81957069:C:A	G234V	0.999
17:81957069:C:T	G234E	0.999
17:81957070:C:A	G234W	0.999
17:81957813:C:A	G230W	0.999
17:81958365:A:G	W188R	0.999
17:81958365:A:T	W188R	0.999
17:81958376:G:A	S184F	0.999
17:81958378:G:C	C183W	0.999
17:81958379:C:T	C183Y	0.999
17:81958961:G:C	N169K	0.999
17:81958961:G:T	N169K	0.999
17:81959487:C:A	W152C	0.999
17:81959487:C:G	W152C	0.999
17:81959553:G:C	C130W	0.999
17:81959658:A:G	W120R	0.999
17:81959658:A:T	W120R	0.999
17:81960607:G:C	C101W	0.999
17:81960608:C:A	C101F	0.999
17:81960608:C:G	C101S	0.999
17:81960608:C:T	C101Y	0.999
17:81960609:A:G	C101R	0.999
17:81960609:A:T	C101S	0.999
17:81953263:A:G	W397R	0.998
17:81953263:A:T	W397R	0.998
17:81956985:A:G	L262P	0.998

dbSNP variants (sampled 300 via entrez): RS1000216246 (17:81955292 T>C), RS1000282395 (17:81960151 G>A), RS1000356190 (17:81955024 A>C), RS1001514886 (17:81959670 C>T), RS1001585565 (17:81959456 G>A,T), RS1001845713 (17:81958831 C>T), RS1001920875 (17:81958579 C>T), RS1002069264 (17:81958966 C>A,T), RS1002080934 (17:81963128 C>T), RS1002195450 (17:81962962 A>G), RS1002199236 (17:81955268 A>G), RS1002268202 (17:81953884 C>G,T), RS1002519681 (17:81961801 C>A,T), RS1002531942 (17:81956432 C>A), RS1002593175 (17:81960619 G>A,T)

Disease associations

OMIM: gene MIM:609847 | 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
GCST006479_9	Diverticular disease	7.000000e-06
GCST006585_628	Blood protein levels	3.000000e-06
GCST006988_29	Blond vs. brown/black hair color	1.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease
EFO:0003924	hair color

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3714531 (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: 257,008 (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
CHEMBL113	CAFFEINE	4	200,591
CHEMBL45	MELATONIN	4	56,417

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

ChEMBL bioactivities

644 potent at pChembl≥5 of 783 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.29	IC50	0.051	nM	CHEMBL4796694
10.12	IC50	0.075	nM	CHEMBL4752559
9.72	IC50	0.19	nM	CHEMBL4784029
9.72	IC50	0.19	nM	CHEMBL4757064
9.59	IC50	0.26	nM	CHEMBL4761454
9.59	IC50	0.26	nM	CHEMBL4741570
9.57	IC50	0.27	nM	CHEMBL4787488
9.46	IC50	0.35	nM	CHEMBL4750152
9.40	IC50	0.4	nM	CHEMBL3760062
9.37	IC50	0.43	nM	CHEMBL4747825
9.35	IC50	0.45	nM	CHEMBL4757561
9.34	IC50	0.46	nM	CHEMBL4759088
9.11	IC50	0.78	nM	CHEMBL2426243
9.00	IC50	1	nM	CHEMBL4642625
9.00	IC50	1	nM	CHEMBL3774760
8.96	IC50	1.1	nM	CHEMBL4637176
8.96	IC50	1.1	nM	CHEMBL3774760
8.92	IC50	1.2	nM	CHEMBL4782633
8.85	IC50	1.4	nM	CHEMBL4776064
8.82	IC50	1.5	nM	CHEMBL4642915
8.82	IC50	1.5	nM	CHEMBL4648963
8.80	IC50	1.6	nM	CHEMBL4632439
8.74	IC50	1.8	nM	CHEMBL4793575
8.74	IC50	1.8	nM	CHEMBL4085008
8.70	IC50	2	nM	CHEMBL4754273
8.70	IC50	2	nM	CHEMBL3774528
8.70	IC50	2	nM	CHEMBL5431852
8.70	IC50	2	nM	CHEMBL5397552
8.62	IC50	2.4	nM	CHEMBL4646043
8.59	IC50	2.6	nM	CHEMBL4637948
8.57	IC50	2.7	nM	CHEMBL4648770
8.54	IC50	2.9	nM	CHEMBL4791705
8.54	IC50	2.9	nM	CHEMBL4743027
8.54	IC50	2.9	nM	CHEMBL5818106
8.52	IC50	3	nM	CHEMBL3774528
8.52	IC50	3	nM	CHEMBL4749659
8.52	IC50	3	nM	CHEMBL5756998
8.51	IC50	3.1	nM	CHEMBL4763193
8.49	IC50	3.2	nM	CHEMBL4641132
8.49	IC50	3.2	nM	CHEMBL4637227
8.46	IC50	3.5	nM	CHEMBL4761164
8.44	IC50	3.6	nM	CHEMBL2324854
8.44	IC50	3.6	nM	CHEMBL5806062
8.42	IC50	3.8	nM	CHEMBL4643862
8.41	IC50	3.9	nM	CHEMBL4634865
8.41	IC50	3.9	nM	CHEMBL4641550
8.41	IC50	3.9	nM	CHEMBL4633059
8.40	IC50	4	nM	CHEMBL5078659
8.38	IC50	4.2	nM	CHEMBL4636343
8.37	IC50	4.3	nM	CHEMBL6039960

PubChem BioAssay actives

451 with measured affinity, of 632 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
5-(4-propan-2-ylphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0001	uM
5-(4-tert-butylphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0001	uM
5-[3-(dimethylamino)phenyl]-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0002	uM
5-[4-(dimethylamino)phenyl]-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0002	uM
5-(4-propan-2-yloxyphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0003	uM
5-(3-cyclopropylphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0003	uM
5-(4-cyclopropylphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0003	uM
5-(4-ethylphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0003	uM
6-chloro-8-fluoro-4,5-dihydrobenzo[g][1]benzothiole-2-carboxylic acid	1894741: Inhibition of human Notum using OPTS substrate by fluorescence based assay	ic50	0.0004	uM
5-(3-ethylphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0004	uM
5-[2-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0004	uM
5-[4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0005	uM
5-[3-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0008	uM
2-[5-methyl-6-(trifluoromethyl)thieno[2,3-d]pyrimidin-4-yl]sulfanylacetic acid	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0010	uM
2-(6-chloro-7-cyclopropylthieno[3,2-d]pyrimidin-4-yl)sulfanylacetic acid	1894741: Inhibition of human Notum using OPTS substrate by fluorescence based assay	ic50	0.0010	uM
2-(6-chloro-7-cyclopropylthieno[3,2-d]pyrimidin-4-yl)sulfanyl-1-(6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)ethanone	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0011	uM
5-(3-methoxyphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0012	uM
5-(4-methoxyphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0014	uM
1-[2-(6-chloro-7-cyclopropylthieno[3,2-d]pyrimidin-4-yl)sulfanylacetyl]imidazolidin-4-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0015	uM
1-[2-(6-chloro-7-cyclopropylthieno[3,2-d]pyrimidin-4-yl)sulfanylacetyl]-3-methylimidazolidin-4-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0015	uM
3-methyl-1-[2-[5-methyl-6-(trifluoromethyl)thieno[2,3-d]pyrimidin-4-yl]sulfanylacetyl]imidazolidin-4-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0016	uM
5-(3-chlorophenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0018	uM
5-[4-cyclopropyl-3-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0018	uM
5-(4-methylphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0020	uM
1-[5-chloro-4-(trifluoromethyl)-2,3-dihydroindol-1-yl]ethanone	1996597: Inhibition of human recombinant Notum (81 to T451 residues) expressed in HEK293S cells using OPTS as substrate incubated for 40 mins by microplate reader analysis	ic50	0.0020	uM
1-(4,5-dichloro-2,3-dihydroindol-1-yl)ethanone	1996597: Inhibition of human recombinant Notum (81 to T451 residues) expressed in HEK293S cells using OPTS as substrate incubated for 40 mins by microplate reader analysis	ic50	0.0020	uM
2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetic acid	1894741: Inhibition of human Notum using OPTS substrate by fluorescence based assay	ic50	0.0020	uM
1-[2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetyl]-3-methylimidazolidin-4-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0024	uM
1-[2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetyl]-3-ethylimidazolidin-4-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0026	uM
1-[2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetyl]imidazolidin-4-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0027	uM
5-(3-methylphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0029	uM
5-[3-cyclopropyl-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0029	uM
5-[4-(difluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0030	uM
5-[3-(difluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0031	uM
2-[5-methyl-6-(trifluoromethyl)furo[2,3-d]pyrimidin-4-yl]sulfanylacetic acid	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0032	uM
2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanyl-1-(6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)ethanone	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0032	uM
5-(4-fluorophenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0035	uM
5-(2-methylphenyl)-3H-1,3,4-oxadiazol-2-one	1699766: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay	ic50	0.0036	uM
1-[2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetyl]-3-cyclopropylimidazolidin-4-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0038	uM
3-methyl-1-[2-[5-methyl-6-(trifluoromethyl)furo[2,3-d]pyrimidin-4-yl]sulfanylacetyl]imidazolidin-4-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0039	uM
1-[2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetyl]-3-(2,2,2-trifluoroethyl)imidazolidin-4-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0039	uM
2-[6-methyl-5-(trifluoromethyl)thieno[2,3-d]pyrimidin-4-yl]sulfanylacetic acid	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0039	uM
6-[3-(trifluoromethoxy)phenyl]sulfanyl-2H-[1,2,4]triazolo[4,3-b]pyridazin-3-one	1818616: Inhibition of human Notum (81 to 451 Cys330Ser) using OPTS as substrate incubated for 40 mins by fluorescence based assay	ic50	0.0040	uM
4-[2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetyl]-1-ethylpiperazin-2-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0042	uM
4,5-dideuterio-1-[2,4-dichloro-3-(trifluoromethyl)phenyl]triazole	1910325: Inhibition of human Notum (S81 to T451 residues) Cys330Ser mutant expressed in HEK293S cells using OPTS as substrate incubated for 40 mins by fluorescence based assay	ic50	0.0046	uM
6-(3,4-dichlorophenyl)sulfanyl-2H-[1,2,4]triazolo[4,3-b]pyridazin-3-one	1818616: Inhibition of human Notum (81 to 451 Cys330Ser) using OPTS as substrate incubated for 40 mins by fluorescence based assay	ic50	0.0050	uM
4-[2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetyl]piperazin-2-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0058	uM
2-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetic acid	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0058	uM
6-(3-chlorophenyl)sulfanyl-2H-[1,2,4]triazolo[4,3-b]pyridazin-3-one	1818616: Inhibition of human Notum (81 to 451 Cys330Ser) using OPTS as substrate incubated for 40 mins by fluorescence based assay	ic50	0.0060	uM
4-[2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetyl]-1-methylpiperazin-2-one	1650706: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay	ic50	0.0062	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	decreases expression	2
bisphenol A	affects expression	1
beta-lapachone	decreases expression	1
sulforaphane	decreases expression	1
2-palmitoylglycerol	increases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Naled	affects expression	1
Niclosamide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Asbestos, Serpentine	decreases methylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

60 unique, capped per target: 59 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3762925	Binding	Inhibition of human notum pectinacetylesterase expressed in 293F cells by TCF/LEF CellSensor assay	4H-Thieno[3,2-c]chromene based inhibitors of Notum Pectinacetylesterase. — Bioorg Med Chem Lett
CHEMBL4610984	ADMET	Stability of the compound assessed as human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells mediated drug hydrolysis measured up to 72 hrs by UPLC-MS analysis	Scaffold-hopping identifies furano[2,3-d]pyrimidine amides as potent Notum inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.