MGAM

Summary

MGAM (maltase-glucoamylase, HGNC:7043) is a protein-coding gene on chromosome 7q34, encoding Maltase-glucoamylase (O43451). Alpha-(1,4) exo-glucosidase involved in breakdown of dietary starch oligosaccharides in small intestine.

This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities.

Source: NCBI Gene 8972 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 442 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001365693

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7043
Approved symbol	MGAM
Name	maltase-glucoamylase
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	MGA
Ensembl gene	ENSG00000257335
Ensembl biotype	protein_coding
OMIM	154360
Entrez	8972

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000465654, ENST00000475668, ENST00000485078, ENST00000490593, ENST00000495045, ENST00000497554, ENST00000497673, ENST00000549489, ENST00000620571

RefSeq mRNA: 2 — MANE Select: NM_001365693 NM_001365693, NM_004668

CCDS: CCDS47727, CCDS94221

Canonical transcript exons

ENST00000475668 — 71 exons

Exon	Start	End
ENSE00001818966	142092521	142092608
ENSE00001832029	142074085	142074173
ENSE00001850877	142105814	142106747
ENSE00002324606	142034262	142034379
ENSE00002328378	142021586	142021737
ENSE00002329027	142050235	142050284
ENSE00002329779	142065715	142065831
ENSE00002331819	142008506	142008705
ENSE00002334796	142094620	142094654
ENSE00002339214	142054754	142054908
ENSE00002345578	142027115	142027227
ENSE00002348689	142005529	142005657
ENSE00002352659	142076203	142076252
ENSE00002354609	142034670	142034841
ENSE00002356075	142095565	142095713
ENSE00002356222	142064384	142064522
ENSE00002356336	142070994	142071118
ENSE00002358464	142062568	142062702
ENSE00002359894	142031680	142031793
ENSE00002362313	142038531	142038615
ENSE00002362803	142025050	142025149
ENSE00002364176	142030362	142030493
ENSE00002366714	142052784	142052984
ENSE00002367535	142065335	142065468
ENSE00002368443	142068647	142068703
ENSE00002368672	142059856	142059966
ENSE00002374370	142060311	142060373
ENSE00002376143	142052294	142052446
ENSE00002379406	142036169	142036285
ENSE00002379515	142027610	142027735
ENSE00002383246	142056000	142056096
ENSE00002386100	142067341	142067425
ENSE00002386400	142097593	142097649
ENSE00002387299	142096331	142096415
ENSE00002387471	142040722	142040846
ENSE00002387976	142065588	142065622
ENSE00002389906	142058203	142058328
ENSE00002390626	142059472	142059600
ENSE00002393509	142050697	142050864
ENSE00002394390	142032825	142032909
ENSE00002409876	142055558	142055726
ENSE00002413665	142022268	142022439
ENSE00002415433	142094747	142094863
ENSE00002417677	142020974	142021083
ENSE00002417822	142040115	142040171
ENSE00002418251	142066573	142066721
ENSE00002421089	142036823	142036977
ENSE00002421241	142063499	142063586
ENSE00002425708	142056830	142056942
ENSE00002426637	142047785	142047873
ENSE00002428067	141995879	141995930
ENSE00002429500	142019199	142019319
ENSE00002448653	142078808	142079008
ENSE00002460656	142080791	142080945
ENSE00002472771	142094364	142094497
ENSE00002473341	142093412	142093550
ENSE00002474496	142083301	142083413
ENSE00002474899	142076659	142076826
ENSE00002476635	142082042	142082210
ENSE00002485655	142086218	142086328
ENSE00002503821	142084519	142084644
ENSE00002511219	142086655	142086717
ENSE00002517705	142078318	142078470
ENSE00002520241	142091913	142092047
ENSE00002522829	142082475	142082571
ENSE00002529874	142085833	142085961
ENSE00003349795	142102630	142102679
ENSE00003382563	142103269	142103439
ENSE00003453996	142100802	142100890
ENSE00003458194	142099613	142099737
ENSE00003647401	142030641	142030757

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 97.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1764 / max 759.8960, expressed in 175 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81568	0.6836	16
81570	0.2566	113
81569	0.0998	59
81565	0.0458	7
81567	0.0445	10
81564	0.0191	4
81571	0.0178	8
81566	0.0092	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	97.17	gold quality
blood	UBERON:0000178	94.17	gold quality
bone marrow cell	CL:0002092	88.78	gold quality
bone marrow	UBERON:0002371	87.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.58	gold quality
small intestine	UBERON:0002108	85.16	gold quality
spleen	UBERON:0002106	82.02	gold quality
right lung	UBERON:0002167	78.07	gold quality
granulocyte	CL:0000094	77.55	gold quality
adult mammalian kidney	UBERON:0000082	77.12	gold quality
kidney	UBERON:0002113	76.28	gold quality
leukocyte	CL:0000738	75.60	gold quality
monocyte	CL:0000576	74.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.46	gold quality
cortex of kidney	UBERON:0001225	70.98	gold quality
upper lobe of left lung	UBERON:0008952	69.66	gold quality
vermiform appendix	UBERON:0001154	67.48	gold quality
lung	UBERON:0002048	66.20	gold quality
gall bladder	UBERON:0002110	65.97	gold quality
metanephros cortex	UBERON:0010533	65.27	gold quality
ascending aorta	UBERON:0001496	61.55	gold quality
descending thoracic aorta	UBERON:0002345	61.31	gold quality
thoracic aorta	UBERON:0001515	61.27	gold quality
islet of Langerhans	UBERON:0000006	61.22	gold quality
testis	UBERON:0000473	61.13	gold quality
left testis	UBERON:0004533	60.63	gold quality
ventricular zone	UBERON:0003053	60.09	gold quality
right testis	UBERON:0004534	59.83	gold quality
popliteal artery	UBERON:0002250	59.77	gold quality
tibial artery	UBERON:0007610	59.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	63.65
E-ANND-3	yes	4.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX2, CREB1, HNF1A, ZNF804A

Literature-anchored findings (GeneRIF, showing 13)

• genetic analysis of MGAM, exon boundaries, and chromosome mapping (PMID:12547908)
• Raw starch granule degradation with recombinanat human MGAM indicates that pancreatic alpha-amylase hydrolysis is not a requirement for native starch digestion in the human small intestine. (PMID:17485087)
• Intestinal maltase-glycoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. (PMID:18036614)
• Acarbose has been found to improve insulin levels and thus glucose/insulin ratios more effectively in overweight patients compared with nonoverweight patients with PCOS. (PMID:18377903)
• This study reported the first diagnosed Finnish patient with a phenotype compatible with the late-onset form of Pompe disease. Molecular genetic analysis of the GAA gene revealed a novel missense mutation (Y575X),combined with (P545L) mutation. (PMID:19472353)
• analysis of substrate selectivity of human maltase-glucoamylase and sucrase-isomaltase N-terminal domains (PMID:20356844)
• These results suggest that the N-terminal and C-terminal catalytic domains of maltase-glucoamylase differ in their substrate specificities and inhibitor tolerance despite their structural relationship (PMID:22036121)
• we report crystal structures of C-terminal maltase-glucoamylase alone at a resolution of 3.1 angstroms, and in complex with its inhibitor acarbose (PMID:22058037)
• Findings suggest that C-terminal subunits of recombinant maltase-glucoamylase (MGAM) assists alpha-amylase in digesting starch molecules and potentially may compensate for developmental or pathological amylase deficiencies. (PMID:22563462)
• The over-expression of MGAM was confirmed with a 6.6 fold increase in expression at the mRNA level whereas the fold change in ADAM9 demonstrated a 1.6 fold increase. (PMID:23405089)
• Starch internal structure modulates its susceptibility to MGAM. The internal branch amounts negatively affect the glucose release rate. (PMID:25037326)
• MGAM, or nearby regulatory elements, may be involved in the etiology of oral clefts. (PMID:25776870)
• Mechanistic Pathway on Human alpha-Glucosidase Maltase-Glucoamylase Unveiled by QM/MM Calculations (PMID:29548257)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-236l14.4	ENSDARG00000062059
danio_rerio		ENSDARG00000104569
mus_musculus	Mgam	ENSMUSG00000068587
rattus_norvegicus	Mgam2	ENSRNOG00000026177
drosophila_melanogaster	GCS2alpha	FBGN0027588
drosophila_melanogaster	tobi	FBGN0261575
caenorhabditis_elegans		WBGENE00018682
caenorhabditis_elegans		WBGENE00019895

Paralogs (6): GANAB (ENSG00000089597), SI (ENSG00000090402), MYORG (ENSG00000164976), GAA (ENSG00000171298), GANC (ENSG00000214013), MGAM2 (ENSG00000257743)

Protein

Protein identifiers

Maltase-glucoamylase — O43451 (reviewed: O43451)

Alternative names: Alpha-1,4-glucosidase

All UniProt accessions (3): E7EW87, E9PEQ5, O43451

UniProt curated annotations — full annotation on UniProt →

Function. Alpha-(1,4) exo-glucosidase involved in breakdown of dietary starch oligosaccharides in small intestine. Cleaves the non-reducing alpha-(1,4)-linked glucose residue in linear dextrins with retention of anomeric center stereochemistry. Mainly hydrolyzes short length oligomaltoses having two to seven glucose residues. Can cleave alpha-(1,2), alpha-(1,3) and alpha-(1,6) glycosidic linkages with lower efficiency, whereas beta glycosidic linkages are usually not hydrolyzed.

Subunit / interactions. Monomer.

Subcellular location. Apical cell membrane.

Tissue specificity. Broadly expressed. Highly expressed in small intestine. Expressed in granulocytes.

Post-translational modifications. N- and O-glycosylated. Does not undergo intracellular or extracellular proteolytic cleavage. Sulfated.

Activity regulation. Down-regulated at high oligomaltose concentration as it occurs during the mealtime. Down-regulated by anti-diabetic drug acarbose.

Domain organisation. The N-terminal maltase domain (ntMGAM) mainly hydrolyzes short length oligomaltoses having two to four glucose residues. The C-terminal glucoamylase domain (ctMGAM) acts on longer maltoside substrates having four to seven glucose residues.

Pathway. Carbohydrate degradation.

Miscellaneous. The displayed isoform 2 sequence is inferred based on alignments, homology, conservation, expression and longest protein. RNA-seq transcriptomic analysis supports all introns in a single sample. No single full-size mRNA sequence supports this isoform yet, however it is clearly identified by mass spectrometry analysis.

Similarity. Belongs to the glycosyl hydrolase 31 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43451-2	2	yes
O43451-1	1

RefSeq proteins (2): NP_001352622, NP_004659 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000322	Glyco_hydro_31_TIM	Domain
IPR000519	P_trefoil_dom	Domain
IPR011013	Gal_mutarotase_sf_dom	Homologous_superfamily
IPR013780	Glyco_hydro_b	Homologous_superfamily
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR017957	P_trefoil_CS	Conserved_site
IPR025887	Glyco_hydro_31_N_dom	Domain
IPR030458	Glyco_hydro_31_AS	Active_site
IPR030459	Glyco_hydro_31_CS	Conserved_site
IPR044913	P_trefoil_dom_sf	Homologous_superfamily
IPR048395	Glyco_hydro_31_C	Domain

Pfam: PF00088, PF01055, PF13802, PF21365

Enzyme classification (BRENDA):

• EC 3.2.1.20 — alpha-glucosidase (BRENDA: 138 organisms, 507 substrates, 642 inhibitors, 449 Km, 159 kcat entries)
• EC 3.2.1.3 — glucan 1,4-alpha-glucosidase (BRENDA: 103 organisms, 422 substrates, 332 inhibitors, 393 Km, 181 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
MALTOSE	0.135–100	94
MALTOSE	0.101–27.4	62
MALTOTRIOSE	0.18–26.7	39
MALTOTRIOSE	0.16–10.6	30
STARCH	0.0002–10	30
ISOMALTOSE	0.455–56	27
MALTOHEPTAOSE	0.025–7.59	27
MALTOTETRAOSE	0.1–25	25
ISOMALTOSE	2.41–59	24
MALTOTETRAOSE	0.032–9.9	23
MALTOPENTAOSE	0.14–63	22
MALTOPENTAOSE	0.03–6.66	22
4-NITROPHENYL ALPHA-D-GLUCOPYRANOSIDE	0.23–13	21
MALTOHEXAOSE	0.045–7.43	20
GLYCOGEN	0.0005–1100	17

Catalyzed reactions (Rhea), 10 shown:

• D-maltotriose + H2O = D-maltose + alpha-D-glucose (RHEA:27970)
• D-maltotetraose + H2O = D-maltotriose + alpha-D-glucose (RHEA:29631)
• D-maltopentaose + H2O = D-maltotetraose + alpha-D-glucose (RHEA:29635)
• D-maltohexaose + H2O = D-maltopentaose + alpha-D-glucose (RHEA:29639)
• D-maltoheptaose + H2O = D-maltohexaose + alpha-D-glucose (RHEA:29643)
• D-maltose + H2O = alpha-D-glucose + D-glucose (RHEA:68796)
• nigerose + H2O = alpha-D-glucose + D-glucose (RHEA:68800)
• kojibiose + H2O = alpha-D-glucose + D-glucose (RHEA:68804)
• 6-O-alpha-D-glucopyranosyl-D-fructose + H2O = alpha-D-glucose + D-fructose (RHEA:68808)
• isomaltose + H2O = alpha-D-glucose + D-glucose (RHEA:68864)

UniProt features (247 total): strand 114, helix 48, turn 23, glycosylation site 20, disulfide bond 8, active site 5, binding site 5, sequence variant 4, mutagenesis site 4, modified residue 3, domain 3, region of interest 3, topological domain 2, chain 1, compositionally biased region 1, transmembrane region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
3L4Y	X-RAY DIFFRACTION	1.8
2QMJ	X-RAY DIFFRACTION	1.9
3L4T	X-RAY DIFFRACTION	1.9
3L4U	X-RAY DIFFRACTION	1.9
3L4X	X-RAY DIFFRACTION	1.9
2QLY	X-RAY DIFFRACTION	2
3L4W	X-RAY DIFFRACTION	2
3L4Z	X-RAY DIFFRACTION	2
3CTT	X-RAY DIFFRACTION	2.1
3L4V	X-RAY DIFFRACTION	2.1
3TOP	X-RAY DIFFRACTION	2.88
3TON	X-RAY DIFFRACTION	2.95

Predicted structure (AlphaFold)

No AlphaFold model available for O43451 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (5): 529 (nucleophile); 532; 1420 (nucleophile); 1423; 1526 (proton donor)

Ligand- & substrate-binding residues (5): 289; 413; 612; 628; 686

Post-translational modifications (3): 416, 425, 1282

Disulfide bonds (8): 90–118, 101–117, 112–130, 659–670, 966–983, 978–996, 1862–1879, 1874–1892

Glycosylation sites (20): 135, 295, 457, 458, 479, 707, 749, 827, 885, 912, 977, 989, 1255, 1323, 1364, 1388, 2499, 2568, 2738, 2743

Mutagenesis-validated functional residues (4):

Position	Phenotype
385	decreases alpha-1,4-glucosidase activity toward maltose.
529	loss of alpha-1,4-glucosidase activity toward maltose.
1251	decreases alpha-1,4-glucosidase activity toward maltose.
1357–1377	decreases alpha-1,4-glucosidase activity toward long oligomaltose substrates having four to seven d-glucose residues.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-189085	Digestion of dietary carbohydrate
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-8935690	Digestion
R-HSA-8963743	Digestion and absorption

MSigDB gene sets: 342 (showing top): GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, REACTOME_DIGESTION_OF_DIETARY_CARBOHYDRATE, MORF_BRCA1, MORF_ATRX, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_OLIGOSACCHARIDE_CATABOLIC_PROCESS, HNF1_Q6, MORF_ESR1, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, MORF_RAD51L3

GO Biological Process (5): maltose catabolic process (GO:0000025), starch catabolic process (GO:0005983), dextrin catabolic process (GO:1901027), carbohydrate metabolic process (GO:0005975), disaccharide catabolic process (GO:0046352)

GO Molecular Function (11): catalytic activity (GO:0003824), alpha-1,4-glucosidase activity (GO:0004558), oligo-1,6-glucosidase activity (GO:0004574), amylase activity (GO:0016160), carbohydrate binding (GO:0030246), glucan 1,4-alpha-glucosidase activity (GO:0004339), hydrolase activity, hydrolyzing O-glycosyl compounds (GO:0004553), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798), alpha-glucosidase activity (GO:0090599)

GO Cellular Component (7): plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), ficolin-1-rich granule membrane (GO:0101003), extracellular region (GO:0005576), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Digestion	1
Innate Immune System	1
Immune System	1
Digestion and absorption	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
alpha-glucosidase activity	3
glucan catabolic process	2
binding	2
secretory granule membrane	2
tertiary granule	2
cellular anatomical structure	2
maltose metabolic process	1
disaccharide catabolic process	1
starch metabolic process	1
primary metabolic process	1
disaccharide metabolic process	1
oligosaccharide catabolic process	1
molecular_function	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
hydrolase activity, acting on glycosyl bonds	1
catalytic activity	1
hydrolase activity	1
glucosidase activity	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
extracellular vesicle	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

2612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MGAM	AMY2A	P04746	988
MGAM	AMY2B	P19961	986
MGAM	AMY1B	P04745	985
MGAM	DPP4	P27487	885
MGAM	INS	P01308	875
MGAM	MGAM2	Q2M2H8	857
MGAM	MOGS	Q13724	843
MGAM	IDUA	P35475	832
MGAM	SLC5A2	P31639	796
MGAM	GCG	P01275	790
MGAM	ACHE	P22303	785
MGAM	GLP1R	P43220	785
MGAM	TREH	O43280	779
MGAM	BCHE	P06276	771
MGAM	LCT	P09848	767

IntAct

61 interactions, top by confidence:

A	B	Type	Score
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
MGAM	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
MGAM	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
MGAM	SLC18A1	psi-mi:“MI:0915”(physical association)	0.560
MGAM	AQP6	psi-mi:“MI:0915”(physical association)	0.560
GPR42	MGAM	psi-mi:“MI:0915”(physical association)	0.560
MGAM	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
CTLA4	B4GALT5	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
SI	MGAM	psi-mi:“MI:0915”(physical association)	0.400
MGAM		psi-mi:“MI:0915”(physical association)	0.370
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
L3MBTL2	MGAM	psi-mi:“MI:0914”(association)	0.350
PCGF6	UBA6	psi-mi:“MI:0914”(association)	0.350
PRPS1	MGAM	psi-mi:“MI:0914”(association)	0.350
RYBP	MGAM	psi-mi:“MI:0914”(association)	0.350
TMEM74	MGAM	psi-mi:“MI:0914”(association)	0.350
WDR5	ZNF609	psi-mi:“MI:0914”(association)	0.350
YAF2	MGAM	psi-mi:“MI:0914”(association)	0.350
ZNF692	U2SURP	psi-mi:“MI:0914”(association)	0.350
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
BUD13	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
CPSF6	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
DDX52	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
DDX55	U2SURP	psi-mi:“MI:2364”(proximity)	0.270
GNL3	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (14): MGAM (Affinity Capture-MS), MGAM (Affinity Capture-MS), MGAM (Two-hybrid), MGAM (Two-hybrid), MGAM (Two-hybrid), MGAM (Two-hybrid), MGAM (Two-hybrid), MGAM (Two-hybrid), MGAM (Affinity Capture-MS), MGAM (Co-fractionation), MGAM (Co-fractionation), MGAM (Co-fractionation), MGAM (Affinity Capture-MS), MGAM (Two-hybrid)

ESM2 similar proteins: A1CNK4, A1D1E6, A1D1Z9, A1DJ58, A2QAN3, A2QTU5, B0XAA1, B0XMP7, B0XNL6, B0XXE7, B8MZ41, B8N6V7, B8NWY6, B8QGZ3, B9F676, D4B0X3, F4J6T7, O04893, O04931, O43451, O62653, O74254, P14410, P22861, P29064, P38138, P56526, Q0CMA7, Q0CVH2, Q12558, Q2TW69, Q2UCU3, Q2UQV7, Q4WG05, Q4WRH9, Q4WS33, Q4ZHV7, Q5AWI5, Q5BFC4, Q8BVW0

Diamond homologs: A1CNK4, A1D1E6, B0XNL6, B8MZ41, D4B0X3, F4J6T7, O00906, O04893, O04931, O43451, O62653, O74254, P07768, P10253, P14410, P22861, P23739, P29064, P56526, P70699, Q09901, Q0CMA7, Q12558, Q2M2H8, Q2UQV7, Q43763, Q4WRH9, Q5AWI5, Q5R7A9, Q653V7, Q6P7A9, Q92442, Q9C0Y4, Q9MYM4, Q9S7Y7, Q9URX4, P19965, Q9P999, Q8RQU9, Q69ZQ1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZNF804A	“down-regulates quantity by repression”	MGAM	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA Polyadenylation	8	17.1×	4e-06
mRNA Splicing	6	16.1×	1e-04
Processing of Capped Intron-Containing Pre-mRNA	7	14.0×	6e-05
mRNA Splicing - Major Pathway	8	10.7×	6e-05
Dengue Virus-Host Interactions	8	8.9×	1e-04
Metabolism of RNA	7	7.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA processing	7	9.7×	2e-03
mRNA splicing, via spliceosome	6	9.6×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	298
Likely benign	58
Benign	20

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
3573022	NM_001400225.1(MGA):c.2709_2712del (p.Ala905fs)	Pathogenic
3573023	NM_001400225.1(MGA):c.2728C>T (p.Arg910Ter)	Pathogenic
3573024	NM_001400225.1(MGA):c.1673del (p.Asp558fs)	Pathogenic
585331	der(15)t(5:15)(q23.2;q15.1)	Pathogenic
800331	NM_001400225.1(MGA):c.3733G>C (p.Glu1245Gln)	Likely pathogenic

SpliceAI

10828 predictions. Top by Δscore:

Variant	Effect	Δscore
7:141931718:A:AC	donor_gain	1.0000
7:141931719:C:CC	donor_gain	1.0000
7:141931824:CTT:C	acceptor_gain	1.0000
7:141946803:TCAC:T	donor_loss	1.0000
7:141946804:CACCT:C	donor_loss	1.0000
7:141946806:CCT:C	donor_gain	1.0000
7:142005522:A:AG	acceptor_gain	1.0000
7:142005523:T:G	acceptor_gain	1.0000
7:142005527:A:AG	acceptor_gain	1.0000
7:142005527:AG:A	acceptor_loss	1.0000
7:142005528:G:GA	acceptor_gain	1.0000
7:142005528:GA:G	acceptor_gain	1.0000
7:142005528:GAGA:G	acceptor_gain	1.0000
7:142005528:GAGAT:G	acceptor_gain	1.0000
7:142005656:AGGT:A	donor_loss	1.0000
7:142005657:GGTA:G	donor_loss	1.0000
7:142005658:GTAAG:G	donor_loss	1.0000
7:142005659:T:G	donor_loss	1.0000
7:142008488:T:G	acceptor_gain	1.0000
7:142008492:T:TA	acceptor_gain	1.0000
7:142008498:T:TA	acceptor_gain	1.0000
7:142008499:G:A	acceptor_gain	1.0000
7:142008502:A:AG	acceptor_gain	1.0000
7:142008503:T:G	acceptor_gain	1.0000
7:142008504:A:AG	acceptor_gain	1.0000
7:142008505:G:GG	acceptor_gain	1.0000
7:142008505:GC:G	acceptor_gain	1.0000
7:142008505:GCC:G	acceptor_gain	1.0000
7:142008505:GCCC:G	acceptor_gain	1.0000
7:142008505:GCCCC:G	acceptor_gain	1.0000

AlphaMissense

18238 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:142065811:C:G	H1584D	0.999
7:142058256:T:G	C1249W	0.998
7:142059488:A:T	D1279V	0.998
7:142065427:A:T	D1526V	0.998
7:142065736:T:C	F1559L	0.998
7:142065738:C:A	F1559L	0.998
7:142065738:C:G	F1559L	0.998
7:142065806:G:C	R1582T	0.998
7:142065807:A:C	R1582S	0.998
7:142065807:A:T	R1582S	0.998
7:142058258:G:C	R1250P	0.997
7:142059487:G:C	D1279H	0.997
7:142059488:A:C	D1279A	0.997
7:142060314:T:A	W1355R	0.997
7:142060314:T:C	W1355R	0.997
7:142065426:G:C	D1526H	0.997
7:142065431:C:A	N1527K	0.997
7:142065431:C:G	N1527K	0.997
7:142065732:T:G	C1557W	0.997
7:142065812:A:C	H1584P	0.997
7:142065813:C:A	H1584Q	0.997
7:142065813:C:G	H1584Q	0.997
7:142055712:G:C	D1157H	0.996
7:142055713:A:C	D1157A	0.996
7:142055713:A:T	D1157V	0.996
7:142058255:G:A	C1249Y	0.996
7:142059489:C:A	D1279E	0.996
7:142059489:C:G	D1279E	0.996
7:142060316:G:C	W1355C	0.996
7:142060316:G:T	W1355C	0.996

dbSNP variants (sampled 300 via entrez): RS1000039629 (7:142000397 A>G), RS1000080853 (7:142040096 T>C,G), RS1000082852 (7:142089103 T>G), RS1000091148 (7:142003689 T>G), RS1000126274 (7:142102469 C>T), RS1000143390 (7:142083759 T>C), RS1000246112 (7:142104645 C>G), RS1000248016 (7:142007044 C>G,T), RS1000274480 (7:142030538 G>A,T), RS1000438170 (7:141994101 C>G,T), RS1000469022 (7:142069531 G>A,T), RS1000469417 (7:141998839 T>C), RS1000535298 (7:142071364 C>G), RS1000565909 (7:142057403 A>G), RS1000601752 (7:142088655 T>C)

Disease associations

OMIM: gene MIM:154360 | disease phenotypes: MIM:189800, MIM:621065, MIM:254500

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (5): preeclampsia (MONDO:0005081), premature ovarian failure 26 (MONDO:0976129), spindle cell sarcoma (MONDO:0002927), plasma cell myeloma (MONDO:0009693), Tourette syndrome (MONDO:0007661)

Orphanet (3): Preeclampsia (Orphanet:275555), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000786	Primary amenorrhea
HP:0000869	Secondary amenorrhea
HP:0008209	Premature ovarian insufficiency
HP:0008214	Decreased serum estradiol
HP:0008222	Female infertility
HP:0008232	Elevated circulating follicle stimulating hormone level
HP:0011969	Elevated circulating luteinizing hormone level

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001961_2	Anorexia nervosa	2.000000e-07
GCST004185_23	Lung function (FEV1/FVC)	1.000000e-09
GCST004643_8	1,5-anhydroglucitol levels	2.000000e-23
GCST005588_36	Idiopathic dilated cardiomyopathy	5.000000e-07
GCST006948_66	Feeling nervous	1.000000e-08
GCST007431_121	Lung function (FEV1/FVC)	7.000000e-12
GCST007483_49	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3.000000e-11
GCST007487_13	Waist-to-hip ratio adjusted for BMI (additive genetic model)	8.000000e-13
GCST007492_5	Waist-to-hip ratio adjusted for BMI (additive genetic model)	4.000000e-06
GCST007494_13	Waist-to-hip ratio adjusted for BMI (additive genetic model)	6.000000e-07
GCST007500_16	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2.000000e-06
GCST007502_11	Waist-to-hip ratio adjusted for BMI (additive genetic model)	4.000000e-07
GCST90002397_253	Mean spheric corpuscular volume	4.000000e-09
GCST90020029_289	Waist circumference adjusted for body mass index	5.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0008009	1,5 anhydroglucitol measurement
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0009597	feeling nervous measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
D011225	Pre-Eclampsia	C12.050.703.395.249
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2074 (SINGLE PROTEIN), CHEMBL3833502 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 290,838 (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
CHEMBL1029	MIGLUSTAT	4	4,770
CHEMBL110458	MIGALASTAT	4	430
CHEMBL1561	MIGLITOL	4	29,089
CHEMBL404271	ACARBOSE	4	16
CHEMBL476960	VOGLIBOSE	4	78,659
CHEMBL1086997	LUCERASTAT	3	74
CHEMBL50	QUERCETIN	3	74,559
CHEMBL85398	THIAZOLIDINEDIONE	3	54,290
CHEMBL307429	DUVOGLUSTAT	2	4,739
CHEMBL44	GENISTEIN	2	44,212

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 3.2.1.- Glycosidases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
acarbose	Inhibition	8.05	pKi
miglitol	Inhibition	6.0	pKi

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
YPYSCWVRH	IC50	34 nM

ChEMBL bioactivities

651 potent at pChembl≥5 of 1085 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.64	Ki	2.3	nM	CHEMBL432221
8.40	Ki	4	nM	CHEMBL120226
8.31	IC50	4.9	nM	CHEMBL2051983
8.24	IC50	5.8	nM	CHEMBL2374254
8.21	IC50	6.1	nM	CHEMBL3349432
8.00	Ki	10	nM	CHEMBL120488
7.89	IC50	13	nM	CHEMBL2374253
7.82	IC50	15	nM	CHEMBL3349431
7.82	Ki	15	nM	CHEMBL1258643
7.70	IC50	20	nM	CHEMBL5555649
7.70	Ki	20	nM	CHEMBL1277241
7.55	IC50	28	nM	CHEMBL2051761
7.55	Ki	28	nM	CHEMBL332802
7.52	Ki	30	nM	DE-O-SULFONATED KOTALANOL
7.40	IC50	40	nM	DUVOGLUSTAT
7.40	IC50	40	nM	CHEMBL498833
7.40	IC50	40	nM	CHEMBL501355
7.37	IC50	43	nM	CHEMBL3349442
7.37	Ki	43	nM	NEOPONKORANOL
7.30	Ki	50	nM	CHEMBL121283
7.22	IC50	60	nM	CHEMBL2442258
7.22	Ki	60	nM	CHEMBL1277240
7.17	IC50	68	nM	CHEMBL2051762
7.16	IC50	70	nM	CHEMBL2051982
7.16	IC50	70	nM	CHEMBL4538427
7.16	IC50	70	nM	CHEMBL4574481
7.16	IC50	70	nM	CHEMBL4552230
7.16	IC50	70	nM	CHEMBL4451108
7.16	IC50	70	nM	CHEMBL4461780
7.16	IC50	70	nM	CHEMBL4466971
7.16	IC50	70	nM	CHEMBL4448033
7.16	IC50	70	nM	CHEMBL4448529
7.16	IC50	70	nM	CHEMBL4467305
7.16	IC50	70	nM	CHEMBL4461882
7.16	IC50	70	nM	CHEMBL4464119
7.16	IC50	70	nM	CHEMBL4449167
7.16	IC50	70	nM	CHEMBL4549137
7.16	IC50	70	nM	CHEMBL4468520
7.16	IC50	70	nM	CHEMBL4453742
7.16	IC50	70	nM	CHEMBL4547928
7.16	IC50	70	nM	CHEMBL4549180
7.16	IC50	70	nM	CHEMBL4551617
7.16	IC50	70	nM	CHEMBL4535608
7.16	IC50	70	nM	CHEMBL4459113
7.16	IC50	70	nM	CHEMBL4438224
7.16	IC50	70	nM	CHEMBL4468873
7.16	IC50	70	nM	CHEMBL4533762
7.16	IC50	70	nM	CHEMBL4513326
7.16	IC50	70	nM	CHEMBL4448264
7.16	Ki	70	nM	CHEMBL120489

PubChem BioAssay actives

605 with measured affinity, of 1587 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
(1S,2S,3R,4S,5S)-5-[[(2R,3S,4S,5R,6S)-4,5-dihydroxy-6-methoxy-2-methyloxan-3-yl]amino]-1-(hydroxymethyl)cyclohexane-1,2,3,4-tetrol	104666: Inhibitory activity against porcine maltase	ic50	0.0049	uM
(1S,2R,3S,4S,5S)-1-(hydroxymethyl)-5-[[(2R)-2-hydroxy-2-phenylethyl]amino]cyclohexane-1,2,3,4-tetrol	104666: Inhibitory activity against porcine maltase	ic50	0.0058	uM
(1S,2S,3R,4S,5S)-5-[[(1R,2R)-2-hydroxycyclohexyl]amino]-1-(hydroxymethyl)cyclohexane-1,2,3,4-tetrol	104666: Inhibitory activity against porcine maltase	ic50	0.0061	uM
(1S,2S,3R,4S,5S)-1-(hydroxymethyl)-5-[[(1R)-2-hydroxy-1-phenylethyl]amino]cyclohexane-1,2,3,4-tetrol	104666: Inhibitory activity against porcine maltase	ic50	0.0130	uM
(1S,2S,3R,4S,5S)-5-[bis(hydroxymethyl)amino]-1-(hydroxymethyl)cyclohexane-1,2,3,4-tetrol	104666: Inhibitory activity against porcine maltase	ic50	0.0150	uM
(2R,3R,4S,5S)-6-[(2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)thiolan-1-ium-1-yl]hexane-1,2,3,4,5-pentol chloride	516767: Inhibition of human recombinant N-terminal domain of maltase-glucoamylase after 60 mins by glucose oxidase assay	ki	0.0150	uM
N-[(E)-benzylideneamino]-4-[(1-benzyltriazol-4-yl)methoxy]benzamide	2075351: Inhibition of alpha-glucosidase (unknown origin) using p-nitrophenyl-alpha-D-glucopyranoside as substrate	ic50	0.0200	uM
(2S,3R,4R,5S,6S)-7-[(2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)selenolan-1-ium-1-yl]heptane-1,2,3,4,5,6-hexol chloride	536212: Inhibition of human recombinant N-terminal subunit of maltase-glucoamylase after 60 mins by glucose oxidase assay	ki	0.0200	uM
(1S,2S,3R,4S,5S)-5-[[(1R,2S,3S,4S,6S)-4-amino-2,3-dihydroxy-6-methylcyclohexyl]amino]-1-(hydroxymethyl)cyclohexane-1,2,3,4-tetrol	104666: Inhibitory activity against porcine maltase	ic50	0.0280	uM
(2S,3R,4R,5S,6S)-7-[(2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)thiolan-1-ium-1-yl]heptane-1,2,3,4,5,6-hexol chloride	536212: Inhibition of human recombinant N-terminal subunit of maltase-glucoamylase after 60 mins by glucose oxidase assay	ki	0.0300	uM
(2R,3S,5R,6R)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol	37260: Inhibitory activity measured against alpha-glucosidase of rice by colorimetric assay using the D-glucose oxidase-peroxidase method	ic50	0.0400	uM
(2R,3R,4R,5S)-2-(hydroxymethyl)piperidine-3,4,5-triol	240862: Inhibitory concentration against human alpha-glucosidase	ic50	0.0400	uM
(1R,2R,14R,17R,18R,21S,24R,25R,26R)-2,13,13,17,18-pentamethyl-24-prop-1-en-2-yl-11-azaheptacyclo[15.11.0.02,14.04,12.05,10.018,26.021,25]octacosa-4(12),5,7,9-tetraene-21-carboxylic acid	2005243: Inhibition of alpha glucosidase (unknown origin) measured after 60 mins	ic50	0.0400	uM
(1S,2S,3R,4S,5S)-5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylamino]-1-(hydroxymethyl)cyclohexane-1,2,3,4-tetrol	104666: Inhibitory activity against porcine maltase	ic50	0.0430	uM
(2S,3R,4S,5S)-6-[(2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)thiolan-1-ium-1-yl]hexane-1,2,3,4,5-pentol chloride	516767: Inhibition of human recombinant N-terminal domain of maltase-glucoamylase after 60 mins by glucose oxidase assay	ki	0.0430	uM
(2S,3R,4S,5R,6R)-7-[(2R,3R,4R)-3,4-dihydroxy-2-(hydroxymethyl)pyrrolidin-1-yl]heptane-1,2,3,4,5,6-hexol;hydrochloride	536212: Inhibition of human recombinant N-terminal subunit of maltase-glucoamylase after 60 mins by glucose oxidase assay	ki	0.0600	uM
(2R,3R,5S,6R)-2,6-bis(hydroxymethyl)-1-methylpiperidine-3,4,5-triol	37260: Inhibitory activity measured against alpha-glucosidase of rice by colorimetric assay using the D-glucose oxidase-peroxidase method	ic50	0.0600	uM
(1S,2S,3R,4S,5S)-1-(hydroxymethyl)-5-[[(1S,2S,3S,4S,6S)-2,3,4-trihydroxy-6-methylcyclohexyl]amino]cyclohexane-1,2,3,4-tetrol	104666: Inhibitory activity against porcine maltase	ic50	0.0680	uM
3-[4-[(2,4-dichlorophenyl)-[4-[[(2,4-dichlorophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(3-bromophenyl)-[4-[4-[[(3-bromophenyl)-[5-(2-oxochromen-3-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenoxy]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(2,4-dichlorophenyl)-[4-[4-[[(2,4-dichlorophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenyl]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-methylphenyl)-[4-[4-[[(4-methylphenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenyl]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-chlorophenyl)-[4-[[(4-chlorophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-nitrophenyl)-[4-[4-[[(4-nitrophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenyl]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(2,4-dichlorophenyl)-[4-[4-[[(2,4-dichlorophenyl)-[5-(2-oxochromen-3-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenoxy]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(3-bromophenyl)-[4-[[(3-bromophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(3-chlorophenyl)-[4-[4-[[(3-chlorophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenyl]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(3-methoxyphenyl)-[4-[4-[[(3-methoxyphenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenyl]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-chlorophenyl)-[4-[4-[[(4-chlorophenyl)-[5-(2-oxochromen-3-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenoxy]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(3-bromophenyl)-[4-[4-[[(3-bromophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenyl]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[[4-(dimethylamino)phenyl]-[4-[4-[[[4-(dimethylamino)phenyl]-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenyl]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-methylphenyl)-[4-[[(4-methylphenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-nitrophenyl)-[4-[4-[[(4-nitrophenyl)-[5-(2-oxochromen-3-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenoxy]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(3-methoxyphenyl)-[4-[[(3-methoxyphenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[[4-(dimethylamino)phenyl]-[4-[[[4-(dimethylamino)phenyl]-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(3-chlorophenyl)-[4-[[(3-chlorophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-bromophenyl)-[4-[4-[[(4-bromophenyl)-[5-(2-oxochromen-3-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenoxy]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-fluorophenyl)-[4-[[(4-fluorophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[[4-(dimethylamino)phenyl]-[4-[4-[[[4-(dimethylamino)phenyl]-[5-(2-oxochromen-3-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenoxy]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-methylphenyl)-[4-[4-[[(4-methylphenyl)-[5-(2-oxochromen-3-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenoxy]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-bromophenyl)-[4-[4-[[(4-bromophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenyl]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-nitrophenyl)-[4-[[(4-nitrophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
3-[4-[(4-chlorophenyl)-[4-[4-[[(4-chlorophenyl)-[5-(2-oxochromen-4-yl)-2-sulfanylidene-1,3,4-oxadiazol-3-yl]methyl]amino]phenyl]anilino]methyl]-5-sulfanylidene-1,3,4-oxadiazol-2-yl]chromen-2-one	1509489: Inhibition of alpha-glucosidase (unknown origin) using p-nitro phenyl glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0700	uM
(1S,2S,3R,4S,5S)-1-(hydroxymethyl)-5-[[(1S,2S,3S,4R,6S)-2,3,4-trihydroxy-6-methylcyclohexyl]amino]cyclohexane-1,2,3,4-tetrol	104666: Inhibitory activity against porcine maltase	ic50	0.0700	uM
(1S,2S,3R,4S,5S)-5-[[(2S,3S,4S,5R,6S)-4,5-dihydroxy-2-(hydroxymethyl)-6-methoxyoxan-3-yl]amino]-1-(hydroxymethyl)cyclohexane-1,2,3,4-tetrol	104666: Inhibitory activity against porcine maltase	ic50	0.0720	uM
[(2S,3S,4R,5R,6S)-1-[(2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)selenolan-1-ium-1-yl]-2,4,5,6,7-pentahydroxyheptan-3-yl] sulfate	536212: Inhibition of human recombinant N-terminal subunit of maltase-glucoamylase after 60 mins by glucose oxidase assay	ki	0.0800	uM
S-(5-methyl-1,3,4-thiadiazol-2-yl) 5-(3-fluorophenyl)furan-2-carbothioate	1951122: Inhibition of alpha glucosidase (unknown origin)	ic50	0.0820	uM
N-[(Z)-[(5Z)-5-[(4-fluorophenyl)methylidene]-3-(4-methylphenyl)-4-oxo-1,3-thiazolidin-2-ylidene]amino]-2-oxochromene-3-carboxamide	1509481: Inhibition of alpha-glucosidase (unknown origin) using p-nitrophenyl-alpha-d-glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0900	uM
N-[(Z)-[(5Z)-5-[(4-fluorophenyl)methylidene]-3-(2-methylphenyl)-4-oxo-1,3-thiazolidin-2-ylidene]amino]-2-oxochromene-3-carboxamide	1509481: Inhibition of alpha-glucosidase (unknown origin) using p-nitrophenyl-alpha-d-glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0900	uM
N-[(Z)-[(5Z)-5-[(4-fluorophenyl)methylidene]-3-(4-methoxyphenyl)-4-oxo-1,3-thiazolidin-2-ylidene]amino]-2-oxochromene-3-carboxamide	1509481: Inhibition of alpha-glucosidase (unknown origin) using p-nitrophenyl-alpha-d-glucopyranoside as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins	ic50	0.0900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Air Pollutants	increases abundance, increases expression, decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sulforaphane	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
belinostat	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
ponkoranol	decreases activity	1
(+)-JQ1 compound	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, decreases expression	1
Endosulfan	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Methapyrilene	increases methylation	1
Ozone	increases expression, increases abundance	1
Silicon Dioxide	decreases expression	1
Smoke	increases expression	1
Sulfonium Compounds	decreases activity	1

ChEMBL screening assays

253 unique, capped per target: 253 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1007704	Binding	Inhibition of maltase	Sesterterpenoids, terretonins A-D, and an alkaloid, asterrelenin, from Aspergillus terreus. — J Nat Prod

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension