GCKR

Summary

GCKR (glucokinase regulator, HGNC:4196) is a protein-coding gene on chromosome 2p23.3, encoding Glucokinase regulatory protein (Q14397). Regulates glucokinase (GCK) by forming an inactive complex with this enzyme.

This gene encodes a protein belonging to the GCKR subfamily of the SIS (Sugar ISomerase) family of proteins. The gene product is a regulatory protein that inhibits glucokinase in liver and pancreatic islet cells by binding non-covalently to form an inactive complex with the enzyme. This gene is considered a susceptibility gene candidate for a form of maturity-onset diabetes of the young (MODY).

Source: NCBI Gene 2646 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 296 total
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_001486

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4196
Approved symbol	GCKR
Name	glucokinase regulator
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000084734
Ensembl biotype	protein_coding
OMIM	600842
Entrez	2646

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264717, ENST00000411584, ENST00000417872, ENST00000453813, ENST00000472290, ENST00000478147, ENST00000867121, ENST00000867122, ENST00000867123, ENST00000867124, ENST00000867125, ENST00000867126, ENST00000867127, ENST00000867128, ENST00000867129

RefSeq mRNA: 1 — MANE Select: NM_001486 NM_001486

CCDS: CCDS1757

Canonical transcript exons

ENST00000264717 — 19 exons

Exon	Start	End
ENSE00001673841	27508168	27508251
ENSE00001683335	27507681	27507777
ENSE00001683451	27506481	27506579
ENSE00001688510	27506788	27506885
ENSE00001723706	27523269	27523684
ENSE00001729178	27507235	27507311
ENSE00001747586	27522460	27522594
ENSE00001767541	27518788	27518937
ENSE00001849469	27496839	27496964
ENSE00003522297	27505718	27505836
ENSE00003536679	27498724	27498797
ENSE00003566618	27498255	27498323
ENSE00003578255	27499397	27499450
ENSE00003607555	27499142	27499208
ENSE00003643963	27507977	27508074
ENSE00003660414	27497244	27497399
ENSE00003671670	27497562	27497630
ENSE00003683244	27503514	27503619
ENSE00003684529	27501135	27501229

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 98.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4711 / max 89.5846, expressed in 97 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19375	0.3722	91
19376	0.0990	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.94	gold quality
liver	UBERON:0002107	93.59	gold quality
left adrenal gland cortex	UBERON:0035825	87.92	gold quality
left adrenal gland	UBERON:0001234	87.10	gold quality
right adrenal gland	UBERON:0001233	87.09	gold quality
left ovary	UBERON:0002119	85.58	gold quality
right adrenal gland cortex	UBERON:0035827	85.44	gold quality
adrenal cortex	UBERON:0001235	84.75	gold quality
right ovary	UBERON:0002118	83.98	gold quality
pancreatic ductal cell	CL:0002079	82.87	silver quality
mucosa of stomach	UBERON:0001199	81.90	gold quality
adrenal gland	UBERON:0002369	81.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.97	gold quality
lower esophagus mucosa	UBERON:0035834	80.92	gold quality
body of stomach	UBERON:0001161	80.32	gold quality
islet of Langerhans	UBERON:0000006	79.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.75	gold quality
buccal mucosa cell	CL:0002336	78.55	silver quality
ovary	UBERON:0000992	77.42	gold quality
stomach	UBERON:0000945	75.92	gold quality
gall bladder	UBERON:0002110	75.84	gold quality
right testis	UBERON:0004534	73.63	gold quality
left testis	UBERON:0004533	73.58	gold quality
pancreas	UBERON:0001264	71.04	gold quality
testis	UBERON:0000473	70.34	gold quality
esophagus mucosa	UBERON:0002469	70.15	gold quality
body of pancreas	UBERON:0001150	69.54	gold quality
descending thoracic aorta	UBERON:0002345	69.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	68.79	gold quality
cerebellar hemisphere	UBERON:0002245	68.50	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	16.21
E-ANND-3	no	3.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOSL2, JUND, SOX4

miRNA regulators (miRDB)

13 targeting GCKR, 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-3162-3P	100.00	65.37	363
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-3620-5P	97.42	63.95	792
HSA-MIR-12115	94.19	66.37	738

Literature-anchored findings (GeneRIF, showing 40)

• Mutations in GKRP are found in the French population, but they do not account for the linkage between the 2p23 locus and quantitative markers of obesity. (PMID:12739015)
• The inhibition of glucokinase by rat and human GKRP are compared. (PMID:14627435)
• The alteration in glucokinase (GK) activity caused by polymorphic activating mutations may have a more profound biological impact than the alleviation of inhibition caused by interaction with GKRP. (PMID:17082186)
• Different type 2 doabetes mutations impair glucokinase function through different mechanisms such as enzymatic activity, protein stability and increased interaction with the flucokinase receptor (PMID:17186219)
• Deletions are detected in exons are investigated in maturity-onset diabetes of the young. (PMID:17828387)
• GCKR rs780094 polymorphism may increase glucokinase regulatory protein activity to induce improved glycaemic regulation at the expense of hypertriacylglycerolaemia (PMID:18008060)
• Data show thatP446L polymorphism carriers are protected against type 2 diabetes despite higher triglyceride levels and risk of dyslipidemia. (PMID:18556336)
• Data show that common missense variant in the glucokinase regulatory protein gene is associated with increased plasma triglyceride and C-reactive protein but lower fasting glucose concentrations. (PMID:18678614)
• SNPs in GCKR and APOA5 have an additive effect on both fasting and postprandial triacylglycerol and contribute to the interindividual variability in response to fenofibrate treatment. (PMID:19056598)
• This protein and glucokinase increase fasting blood glucose and risk of diabetics who have other risk factors. (PMID:19073768)
• GCKR polymorphism contributes to the risk of type 2 diabetes and dyslipidaemia in Han Chinese individuals. (PMID:19241058)
• Glucokinase regulatory protein gene polymorphism is associated with postprandial triglyceridemia. (PMID:19526250)
• Variations and single-nucleotide polymorphisms are nott associated in variations in fasting plasma glucose and an increased risk of type 2 diabetes. (PMID:19533084)
• Data show that assays matched for GKRP activity demonstrated no difference in dose-dependent inhibition of GCK activity or F1P-mediated regulation. (PMID:19643913)
• Data show that SNPs associated with TG in normolipidemic samples, including APOA5, TRIB1, TBL2, GCKR, GALNT2 and ANGPTL3 were significantly associated with HLP types 2B, 3, 4 and 5. (PMID:19656773)
• Results describe the association of the functional variants of glucokinase regulatory protein and apolipoprotein A5 genes with non-fasting triglyceride levels and their susceptibility nature in ischemic stroke. (PMID:19847674)
• Fasting glucose association at GCKR is replicable across ethnic groups, although ethnic diversity in the pattern and strength of linkage disequilibrium exists. (PMID:19937311)
• GCKR polymorphisms increase plasma levels of triglycerides and free fatty acids, but do not elevate cardiovascular risk. (PMID:20352598)
• the GCKR rs780094 polymorphism is associated with susceptibility of type 2 diabetes, reduced fasting plasma glucose levels, increased triglycerides levels and lower HOMA-IR in Japanese population (PMID:20574426)
• the GCKR genotype is associated with non-alcoholic fatty liver disease in Chinese people (PMID:20625834)
• Findings indicate rs780094 in GCKR has independent associations with multiple metabolic traits as well as incident diabetes, but not incident CHD or stroke. (PMID:20661421)
• Study showed that SNPs from GCK, G6PC2 and MTNR1B modulated the fasting glucose levels in the normoglycaemic population while SNPs from G6PC2 and GCKR was associated with type 2 diabetes. (PMID:20668700)
• GCKR genotypes had effect on triglycerides, remnant cholesterol, and apolipoprotein B levels. (PMID:21071687)
• GCKR gene variants inversely associated with serum triglycerides/fasting plasma glucose levels in type 2 diabetes and metabolic syndrome. Suggest cardiovascular risk role of GCKR minor allele carriage based on carotid intima-media thickness association. (PMID:21114848)
• glucokinase regulator is a susceptibility gene in Japanese families with clustered diabetes (PMID:21236713)
• Data show that a novel polymorphism (rs4425043) in the GCKR gene increases the risk of overweight and obesity in Chinese women. (PMID:21318467)
• Findings are compatible with the idea that GCKR variability may play a pathogenetic role in both type 2 diabetes and CKD. (PMID:21411509)
• pharmacological manipulation of GCK activity at locations distal from the allosteric activator site is possible. (PMID:21454522)
• Our findings confirm the inverse modulating effect of functional GCKR variants on triglycerides and glucose levels in obese paediatric patients and healthy normal-weight controls. (PMID:21511510)
• The rs3817588 A/G polymorphism of the glucokinase regulatory protein gene was associated with type 2 diabetes and plasma triglyceride level in the Han Chinese population. (PMID:21569451)
• Evidence for the existence of rare APOA5 and GCKR haplotypes in metabolic syndrome patients with higher triglyceride levels, which contribute to the complex lipid metabolism alteration in this disease. (PMID:21643755)
• a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in metabolic syndrome (PMID:21674002)
• The role of four loci (ADCY5, GIPR, GCKR and VPS13C) in early impairment of glucose and insulin metabolism in children, was investigated. (PMID:21789219)
• Study provides evidence that GCKR rs780094, a single-nucleotide polymorphism related to diabetes, may be associated with pancreatic cancer risk. (PMID:22015968)
• Data suggest that GCKR P446L variant (an SNP [rs1260326] associated with type 2 diabetes risk) alters ability of GCKR to sequester glucokinase in nucleus of hepatocytes. (PMID:22038520)
• The rs1260326 in GCKR is associated with hepatic fat accumulation along with large VLDL and triglyceride levels. GCKR and PNPLA3 act together to convey susceptibility to fatty liver in obese youths. (PMID:22105854)
• Defects were observed for the majority of rare variants after assessment of cellular localization, ability to interact with GCK, and kinetic activity of the encoded proteins. Functional rare variants showed associations with lipid phenotypes. (PMID:22182842)
• 2 SNPs, rs780093 and rs780094, located in intronic regions of the GCKR gene were found to be significantly associated with the development of gout in male Han Chinese; GCKR was identified as a novel candidate gene associated with gout (PMID:22395765)
• Essential roles of the polymorphisms of the APOA5, GCK and GCKR in the lipid or glucose metabolism disorders. (PMID:22517333)
• Only one single nucleotide polymorphism of GCKR hyperglycemia was significantly associated with amino acid blood levels, hyperglycemia, and risk for type 2 diabetes. (PMID:22553379)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gckr	ENSDARG00000086620
mus_musculus	Gckr	ENSMUSG00000059434
rattus_norvegicus	Gckr	ENSRNOG00000048874

Protein

Protein identifiers

Glucokinase regulatory protein — Q14397 (reviewed: Q14397)

All UniProt accessions (3): A0A0C4DFN2, H7C1B4, H7C4D3

UniProt curated annotations — full annotation on UniProt →

Function. Regulates glucokinase (GCK) by forming an inactive complex with this enzyme. Acts by promoting GCK recruitment to the nucleus, possibly to provide a reserve of GCK that can be quickly released in the cytoplasm after a meal. The affinity of GCKR for GCK is modulated by fructose metabolites: GCKR with bound fructose 6-phosphate has increased affinity for GCK, while GCKR with bound fructose 1-phosphate has strongly decreased affinity for GCK and does not inhibit GCK activity.

Subunit / interactions. Interacts (fructose 6-phosphate bound form) with GCK.

Subcellular location. Cytoplasm. Nucleus. Mitochondrion.

Tissue specificity. Found in liver and pancreas. Not detected in muscle, brain, heart, thymus, intestine, uterus, adipose tissue, kidney, adrenal, lung or spleen.

Domain organisation. Fructose 1-phosphate and fructose 6-phosphate compete for the same binding site.

Polymorphism. Genetic variations in GCKR define the fasting plasma glucose levels quantitative trait locus 5 (FGQTL5) [MIM:613463]. The normal fasting plasma glucose level is defined as less than 100 mg glucose per deciliter plasma (5.55 mmol per liter). Higher fasting plasma glucose levels predict type 2 diabetes in young adults and increases the risk of mortality.

Similarity. Belongs to the GCKR family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14397-1	1	yes
Q14397-2	2

RefSeq proteins (1): NP_001477* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001347	SIS_dom	Domain
IPR005486	Glucokinase_regulatory_CS	Conserved_site
IPR040190	MURQ/GCKR	Family
IPR046348	SIS_dom_sf	Homologous_superfamily
IPR054017	GKRP_SIS_2	Domain

Pfam: PF20741, PF22198, PF22645

UniProt features (82 total): helix 33, strand 14, turn 9, binding site 8, sequence variant 4, mutagenesis site 4, sequence conflict 3, domain 2, splice variant 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
4BB9	X-RAY DIFFRACTION	1.47
4BBA	X-RAY DIFFRACTION	1.92
4PX2	X-RAY DIFFRACTION	2.15
4MRO	X-RAY DIFFRACTION	2.2
4PX5	X-RAY DIFFRACTION	2.2
4MQU	X-RAY DIFFRACTION	2.22
4OP2	X-RAY DIFFRACTION	2.24
4LY9	X-RAY DIFFRACTION	2.35
4OP1	X-RAY DIFFRACTION	2.39
4OHM	X-RAY DIFFRACTION	2.4
4OHP	X-RAY DIFFRACTION	2.4
4OLH	X-RAY DIFFRACTION	2.4
4PX3	X-RAY DIFFRACTION	2.43
4MSU	X-RAY DIFFRACTION	2.5
4OHO	X-RAY DIFFRACTION	2.58
4PXS	X-RAY DIFFRACTION	2.6
4OHK	X-RAY DIFFRACTION	2.8
4OP3	X-RAY DIFFRACTION	2.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14397-F1	93.26	0.88

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 (8): 348; 514; 514; 109–110; 109–110; 153; 179–181; 179–181

Mutagenesis-validated functional residues (4):

Position	Phenotype
326–327	no effect on inhibition of glucokinase.
413	impairs inhibition of glucokinase.
450–451	impairs inhibition of glucokinase.
463–465	abolishes interaction with gck. abolishes inhibition of gck.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-170822	Regulation of Glucokinase by Glucokinase Regulatory Protein
R-HSA-5619107	Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)

MSigDB gene sets: 116 (showing top): GOBP_ACYLGLYCEROL_HOMEOSTASIS, MOOTHA_GLYCOGEN_METABOLISM, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_LIPID_HOMEOSTASIS, GOBP_NUCLEAR_TRANSPORT, BOYAULT_LIVER_CANCER_SUBCLASS_G12_DN, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_NEGATIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION

GO Biological Process (9): intracellular glucose homeostasis (GO:0001678), protein import into nucleus (GO:0006606), response to glucose (GO:0009749), response to fructose (GO:0009750), negative regulation of glucokinase activity (GO:0033132), protein localization to nucleus (GO:0034504), urate metabolic process (GO:0046415), triglyceride homeostasis (GO:0070328), carbohydrate derivative metabolic process (GO:1901135)

GO Molecular Function (10): kinase inhibitor activity (GO:0019210), fructose-6-phosphate binding (GO:0070095), glucose sensor activity (GO:0141089), enzyme inhibitor activity (GO:0004857), kinase activity (GO:0016301), enzyme binding (GO:0019899), kinase binding (GO:0019900), protein domain specific binding (GO:0019904), carbohydrate binding (GO:0030246), carbohydrate derivative binding (GO:0097367)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glycolysis	1
SLC transporter disorders	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
response to hexose	2
protein binding	2
binding	2
cytoplasm	2
intracellular membrane-bounded organelle	2
glucose homeostasis	1
intracellular chemical homeostasis	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
glucokinase activity	1
negative regulation of kinase activity	1
protein localization to organelle	1
small molecule metabolic process	1
purine-containing compound metabolic process	1
acylglycerol homeostasis	1
metabolic process	1
enzyme inhibitor activity	1
kinase activity	1
kinase regulator activity	1
anion binding	1
carbohydrate derivative binding	1
D-glucose binding	1
molecular sensor activity	1
catalytic activity	1
enzyme regulator activity	1
molecular function inhibitor activity	1
transferase activity, transferring phosphorus-containing groups	1
enzyme binding	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GCKR	GCK	P35557	998
GCKR	KHK	P50053	830
GCKR	DGKB	Q9Y6T7	743
GCKR	MTNR1B	P49286	737
GCKR	PNPLA3	Q9NST1	695
GCKR	TM6SF2	Q9BZW4	695
GCKR	G6PC2	Q9NQR9	688
GCKR	INS	P01308	674
GCKR	LYPLAL1	Q5VWZ2	666
GCKR	ADCY5	O95622	618
GCKR	CDKAL1	Q5VV42	616
GCKR	PPP1R3B	Q86XI6	597
GCKR	MBOAT7	Q96N66	596
GCKR	SLC30A8	Q8IWU4	589
GCKR	FTO	Q9C0B1	561

IntAct

9 interactions, top by confidence:

A	B	Type	Score
GCK	GCKR	psi-mi:“MI:0915”(physical association)	0.720
GCKR	GCK	psi-mi:“MI:0407”(direct interaction)	0.720
CDKN1A	GCKR	psi-mi:“MI:0915”(physical association)	0.370
GCKR	CFTR	psi-mi:“MI:0915”(physical association)	0.370
DNHD1	CETN2	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): GCK (Affinity Capture-Western), GCKR (Affinity Capture-Western), SIRT2 (Affinity Capture-Western), EP300 (Affinity Capture-Western), GCKR (Affinity Capture-Western), GCKR (Biochemical Activity), GCKR (Reconstituted Complex), GCK (FRET), GCK (Two-hybrid), GCKR (Affinity Capture-MS), GCK (Two-hybrid), GCKR (PCA), GCKR (Cross-Linking-MS (XL-MS)), GCKR (Cross-Linking-MS (XL-MS)), GCKR (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A8C2MDK8, A7SLX5, A7YY46, D3ZEY4, D3ZX08, E9QAM5, O59713, O95822, P0C7A1, P48760, P52333, P52824, Q002B5, Q07071, Q14397, Q15477, Q2KI24, Q2M296, Q2NKY8, Q3SYT1, Q3T7C9, Q3U1Y4, Q3URQ7, Q4R380, Q52L34, Q567W6, Q568Y2, Q5I0I8, Q5NCQ5, Q5ZHX9, Q6GPQ5, Q6NZR5, Q6P5E8, Q8BUI3, Q8BX80, Q8C9A2, Q8NFF5, Q8NFI3, Q91X44, Q920F5

Diamond homologs: A3N2I4, B0BRD0, B3GYL8, B8F4V1, Q07071, Q14397, Q28KP2, Q91754, Q91X44, C1KVV7, Q71Z09, Q82GH3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	184
Likely benign	69
Benign	21

Top pathogenic / likely-pathogenic (0)

SpliceAI

2653 predictions. Top by Δscore:

Variant	Effect	Δscore
2:27496964:GGTGA:G	donor_loss	1.0000
2:27496965:GTGAG:G	donor_loss	1.0000
2:27496966:T:G	donor_loss	1.0000
2:27497240:CTA:C	acceptor_loss	1.0000
2:27497242:A:AG	acceptor_gain	1.0000
2:27497242:A:AT	acceptor_loss	1.0000
2:27497243:G:GA	acceptor_gain	1.0000
2:27497243:GT:G	acceptor_gain	1.0000
2:27497243:GTT:G	acceptor_gain	1.0000
2:27497243:GTTGT:G	acceptor_gain	1.0000
2:27497395:ACCAG:A	donor_loss	1.0000
2:27497396:CCAG:C	donor_loss	1.0000
2:27497397:CAGG:C	donor_loss	1.0000
2:27497398:AGGT:A	donor_loss	1.0000
2:27497399:GGT:G	donor_loss	1.0000
2:27497400:GTA:G	donor_loss	1.0000
2:27498795:CAGG:C	donor_loss	1.0000
2:27498796:AG:A	donor_loss	1.0000
2:27498797:GG:G	donor_loss	1.0000
2:27498798:G:GC	donor_loss	1.0000
2:27498799:TAAG:T	donor_loss	1.0000
2:27499451:G:GG	donor_gain	1.0000
2:27501127:A:AG	acceptor_gain	1.0000
2:27501128:C:G	acceptor_gain	1.0000
2:27501130:ATCAG:A	acceptor_gain	1.0000
2:27501227:CAG:C	donor_loss	1.0000
2:27501228:AG:A	donor_loss	1.0000
2:27501229:GG:G	donor_loss	1.0000
2:27501231:T:A	donor_loss	1.0000
2:27503504:T:A	acceptor_gain	1.0000

AlphaMissense

4097 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:27518806:A:C	S481R	0.992
2:27518808:C:A	S481R	0.992
2:27518808:C:G	S481R	0.992
2:27501207:T:C	F208L	0.989
2:27501209:C:A	F208L	0.989
2:27501209:C:G	F208L	0.989
2:27505757:A:C	S264R	0.989
2:27505759:T:A	S264R	0.989
2:27505759:T:G	S264R	0.989
2:27498282:A:C	S105R	0.987
2:27498284:T:A	S105R	0.987
2:27498284:T:G	S105R	0.987
2:27518814:A:C	K483N	0.987
2:27518814:A:T	K483N	0.987
2:27501141:T:C	F186L	0.984
2:27501143:T:A	F186L	0.984
2:27501143:T:G	F186L	0.984
2:27518813:A:T	K483I	0.983
2:27518833:A:C	S490R	0.980
2:27518835:T:A	S490R	0.980
2:27518835:T:G	S490R	0.980
2:27505749:A:T	K261I	0.979
2:27505750:A:C	K261N	0.979
2:27505750:A:T	K261N	0.979
2:27498310:C:A	A114E	0.978
2:27507255:T:C	F363L	0.978
2:27507257:T:A	F363L	0.978
2:27507257:T:G	F363L	0.978
2:27508210:T:A	W461R	0.977
2:27508210:T:C	W461R	0.977

dbSNP variants (sampled 300 via entrez): RS1000180397 (2:27506443 A>C,T), RS1000251162 (2:27513130 C>T), RS1000491455 (2:27519994 G>A), RS1000789021 (2:27512693 A>G), RS1000874233 (2:27518046 A>G), RS1000947015 (2:27504165 G>A,T), RS1001054006 (2:27510043 C>A), RS1001183572 (2:27504703 C>T), RS1001299195 (2:27504468 C>G), RS1001396463 (2:27511078 A>C), RS1001648332 (2:27516067 G>A), RS1001656024 (2:27511272 C>T), RS1001692053 (2:27495844 G>A,T), RS1001717844 (2:27504986 C>A,T), RS1001722085 (2:27515750 T>C)

Disease associations

OMIM: gene MIM:600842 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hypertriglyceridemia (MONDO:0005347)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0002155	Hypertriglyceridemia

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015228	Hypertriglyceridemia	C18.452.584.500.500.851

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1075152 (SINGLE PROTEIN), CHEMBL3885579 (PROTEIN-PROTEIN INTERACTION)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1260326	Toxicity	3	ethanol	Alcohol abuse

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs780093	GCKR		0.00	0
rs780094	GCKR		0.00	0
rs1260326	GCKR	3	1.50	1	ethanol

ChEMBL bioactivities

135 potent at pChembl≥5 of 138 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.82	Kd	1.5	nM	CHEMBL3746243
8.42	IC50	3.8	nM	CHEMBL3746243
8.40	IC50	4	nM	CHEMBL3114185
8.38	Kd	4.2	nM	CHEMBL3745887
8.30	IC50	5	nM	CHEMBL3237987
8.22	IC50	6	nM	CHEMBL3237981
8.22	IC50	6	nM	CHEMBL3237986
8.22	IC50	6	nM	CHEMBL3578107
8.22	IC50	6	nM	CHEMBL3745887
8.18	Kd	6.6	nM	CHEMBL3746444
8.15	IC50	7	nM	CHEMBL3578087
8.07	Kd	8.6	nM	CHEMBL3746034
8.05	IC50	9	nM	CHEMBL3114187
8.01	IC50	9.7	nM	CHEMBL3127349
8.00	IC50	10	nM	CHEMBL3238309
8.00	IC50	10	nM	CHEMBL3238310
8.00	IC50	10	nM	CHEMBL3578106
7.96	IC50	11	nM	CHEMBL3746444
7.92	IC50	12	nM	CHEMBL3127352
7.89	IC50	13	nM	CHEMBL3238307
7.89	IC50	13	nM	CHEMBL3238308
7.89	IC50	13	nM	CHEMBL3238313
7.82	IC50	15	nM	CHEMBL3578104
7.82	IC50	15	nM	CHEMBL3578090
7.80	IC50	16	nM	CHEMBL3237985
7.77	IC50	17	nM	CHEMBL3238303
7.77	IC50	17	nM	CHEMBL3746456
7.75	IC50	18	nM	CHEMBL3238306
7.75	IC50	18	nM	CHEMBL3578103
7.75	IC50	18	nM	CHEMBL3746034
7.72	Kd	19	nM	CHEMBL3746456
7.72	Kd	19	nM	CHEMBL3746655
7.68	IC50	21	nM	CHEMBL3113979
7.68	IC50	21	nM	CHEMBL3578080
7.64	IC50	23	nM	CHEMBL3578101
7.62	IC50	24	nM	CHEMBL3238312
7.60	IC50	25	nM	CHEMBL3746655
7.55	IC50	28	nM	CHEMBL3237980
7.55	IC50	28	nM	CHEMBL3237984
7.52	Kd	30	nM	CHEMBL3747365
7.46	IC50	35	nM	CHEMBL3237993
7.44	IC50	36	nM	CHEMBL3127348
7.43	IC50	37	nM	CHEMBL3578102
7.42	IC50	38	nM	CHEMBL3578091
7.38	IC50	42	nM	CHEMBL3578081
7.35	IC50	45	nM	CHEMBL3238301
7.33	IC50	47	nM	CHEMBL3237983
7.31	IC50	49	nM	CHEMBL3238316
7.29	IC50	51	nM	CHEMBL3578100
7.28	IC50	52	nM	CHEMBL3747784

PubChem BioAssay actives

135 with measured affinity, of 230 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-[(R)-(2-amino-5-chloro-3-fluoro-4-pyridinyl)-[7-[4-(2-hydroxypropan-2-yl)-2-pyridinyl]-1-benzothiophen-2-yl]methyl]cyclopropanesulfonamide	1266762: Binding affinity to human GKRP by surface plasmon resonance analysis	kd	0.0015	uM
2-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0040	uM
N-[(R)-(6-amino-3-chloro-2-pyridinyl)-[7-[4-(2-hydroxypropan-2-yl)-2-pyridinyl]-1-benzothiophen-2-yl]methyl]cyclopropanesulfonamide	1266762: Binding affinity to human GKRP by surface plasmon resonance analysis	kd	0.0042	uM
2-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-1,1,1-trifluorohex-4-yn-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0050	uM
(2R)-2-[4-[5-[(6-amino-3-pyridinyl)sulfonyl]-1,3-thiazol-2-yl]-3-chlorophenyl]propane-1,2-diol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0060	uM
2-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-1,1,1-trifluoropent-4-yn-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0060	uM
(2R)-2-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-3,3,3-trifluoropropane-1,2-diol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0060	uM
N-[(R)-(6-amino-3-chloro-5-fluoro-2-pyridinyl)-[7-[4-(2-hydroxypropan-2-yl)-2-pyridinyl]-1-benzothiophen-2-yl]methyl]cyclopropanesulfonamide	1266762: Binding affinity to human GKRP by surface plasmon resonance analysis	kd	0.0066	uM
2-[6-[6-[(6-amino-3-pyridinyl)sulfonyl]-2-anilino-3-pyridinyl]-3-pyridinyl]-1,1,1-trifluoropropan-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0070	uM
N-[(R)-(2-amino-5-chloropyrimidin-4-yl)-[7-[4-(2-hydroxypropan-2-yl)-2-pyridinyl]-1-benzothiophen-2-yl]methyl]cyclopropanesulfonamide	1266762: Binding affinity to human GKRP by surface plasmon resonance analysis	kd	0.0086	uM
(2R)-2-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-1,1,1-trifluoropropan-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0090	uM
1,1,1,3,3,3-hexafluoro-2-[4-[(2S)-2-[[(3S)-3-methylmorpholin-4-yl]methyl]-4-thiophen-2-ylsulfonylpiperazin-1-yl]phenyl]propan-2-ol	1074136: Inhibition of biotin-tagged human GKRP-fluorescein-tagged human GK interaction preincubated for 20 mins followed by fluorescein-tagged human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0097	uM
2-[4-[5-[(6-amino-3-pyridinyl)sulfonyl]-1,3-thiazol-2-yl]-3-chlorophenyl]propane-1,2-diol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0100	uM
2-[6-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0100	uM
2-[2-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]pyrimidin-5-yl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0100	uM
(2S)-1,1,1-trifluoro-2-[4-[(2S)-2-[[(3S)-3-methylmorpholin-4-yl]methyl]-4-thiophen-2-ylsulfonylpiperazin-1-yl]phenyl]propan-2-ol	1074136: Inhibition of biotin-tagged human GKRP-fluorescein-tagged human GK interaction preincubated for 20 mins followed by fluorescein-tagged human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0120	uM
(2R)-2-[6-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]-3-pyridinyl]-1,1,1-trifluoropropan-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0130	uM
(2S)-2-[6-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]-3-pyridinyl]-1,1,1-trifluoropropan-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0130	uM
(2S)-2-[6-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]-3-pyridinyl]-3,3,3-trifluoropropane-1,2-diol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0130	uM
2-[6-[6-[(6-amino-3-pyridinyl)sulfonyl]-2-(pyridin-4-ylamino)-3-pyridinyl]-3-pyridinyl]-1,1,1-trifluoropropan-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0150	uM
2-[4-[5-[(6-amino-3-pyridinyl)sulfonyl]-1,3-thiazol-2-yl]-3-chlorophenyl]propan-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0150	uM
2-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-1,1,1-trifluoro-3-methoxypropan-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0160	uM
N-[(R)-1-benzothiophen-2-yl-(2-chlorophenyl)methyl]-3,4-dihydro-2H-1,5-benzodioxepine-7-sulfonamide	1266769: Binding affinity to human biotinylated AviTag GKRP assessed as inhibition of protein interaction with fluorescein tagged human glucokinase by AlphaScreen assay	ic50	0.0170	uM
5-[(3S)-3-prop-1-ynyl-4-[4-(trifluoromethylsulfonimidoyl)phenyl]piperazin-1-yl]sulfonylpyridin-2-amine	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0170	uM
(2S)-2-[4-[5-[(6-amino-3-pyridinyl)sulfonyl]-1,3-thiazol-2-yl]-3-chlorophenyl]-1,1,1-trifluoropropan-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0180	uM
2-[6-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]-3-pyridinyl]-1,1,1-trifluoropropan-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0180	uM
N-[(R)-(2-amino-5-chloro-4-pyridinyl)-[7-[4-(2-hydroxypropan-2-yl)-2-pyridinyl]-1-benzothiophen-2-yl]methyl]cyclopropanesulfonamide	1266762: Binding affinity to human GKRP by surface plasmon resonance analysis	kd	0.0190	uM
(2R)-1,1,1-trifluoro-2-[4-[(2S)-2-[[(3S)-3-methylmorpholin-4-yl]methyl]-4-thiophen-2-ylsulfonylpiperazin-1-yl]phenyl]propan-2-ol	1074136: Inhibition of biotin-tagged human GKRP-fluorescein-tagged human GK interaction preincubated for 20 mins followed by fluorescein-tagged human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0210	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]phenyl]-5-(3-methoxyprop-1-ynyl)-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0210	uM
2-[4-[5-[(6-amino-3-pyridinyl)sulfonyl]-1,3-thiazol-2-yl]-3-chlorophenyl]-1,1,1-trifluoropropan-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0230	uM
2-[6-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]-3-pyridinyl]-3,3,3-trifluoropropane-1,2-diol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0240	uM
3-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-4,4,4-trifluoro-3-hydroxybutanenitrile	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0280	uM
(2S)-2-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-3,3,3-trifluoropropane-1,2-diol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0280	uM
N-[(R)-(2-chloro-6-fluorophenyl)-[7-[4-(2-hydroxypropan-2-yl)-2-pyridinyl]-1-benzothiophen-2-yl]methyl]cyclopropanesulfonamide	1266762: Binding affinity to human GKRP by surface plasmon resonance analysis	kd	0.0300	uM
4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]-N-methylbenzenesulfonamide	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0350	uM
1,1,1,3,3,3-hexafluoro-2-[4-[(2S)-2-(morpholin-4-ylmethyl)-4-thiophen-2-ylsulfonylpiperazin-1-yl]phenyl]propan-2-ol	1074136: Inhibition of biotin-tagged human GKRP-fluorescein-tagged human GK interaction preincubated for 20 mins followed by fluorescein-tagged human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0360	uM
(2R)-2-[4-[5-[(6-amino-3-pyridinyl)sulfonyl]-1,3-thiazol-2-yl]-3-chlorophenyl]-1,1,1-trifluoropropan-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0370	uM
2-[6-[6-[(6-amino-3-pyridinyl)sulfonyl]-2-(pyridin-3-ylamino)-3-pyridinyl]-3-pyridinyl]-1,1,1-trifluoropropan-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0380	uM
(2S)-4-[2-[4-[(6-amino-3-pyridinyl)sulfonyl]phenyl]-5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-3-pyridinyl]but-3-yn-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0420	uM
5-[(3S)-3-prop-1-ynyl-4-[4-(trifluoromethylsulfonimidoyl)phenyl]piperazin-1-yl]sulfonylpyridin-2-amine	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0450	uM
(2R)-3-amino-2-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-1,1,1-trifluoropropan-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0470	uM
2-[2-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]-1,3-thiazol-5-yl]-1,1,1-trifluoropropan-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0490	uM
2-[6-[5-[(6-amino-3-pyridinyl)sulfonyl]thiophen-2-yl]-5-prop-1-ynyl-3-pyridinyl]-1,1,1-trifluoropropan-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0510	uM
N-[(R)-1-benzofuran-2-yl-(2-chlorophenyl)methyl]-3,4-dihydro-2H-1,5-benzodioxepine-7-sulfonamide	1266769: Binding affinity to human biotinylated AviTag GKRP assessed as inhibition of protein interaction with fluorescein tagged human glucokinase by AlphaScreen assay	ic50	0.0520	uM
1,1,1,3,3,3-hexafluoro-2-[4-[(2S)-2-(oxan-4-ylmethyl)-4-thiophen-2-ylsulfonylpiperazin-1-yl]phenyl]propan-2-ol	1074136: Inhibition of biotin-tagged human GKRP-fluorescein-tagged human GK interaction preincubated for 20 mins followed by fluorescein-tagged human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0580	uM
(2S)-2-[4-[5-[(6-amino-3-pyridinyl)sulfonyl]-1,3-thiazol-2-yl]-3-chlorophenyl]propane-1,2-diol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0610	uM
4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]benzenesulfonamide	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0610	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]phenyl]-5-(3-hydroxyprop-1-ynyl)-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0650	uM
6-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]-N-methylpyridine-3-sulfonamide	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0680	uM
2-[5-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]-2-pyridinyl]-1,1,1-trifluoropropan-2-ol	1129612: Inhibition of biotin-tagged human GKRP/fluorescein-tagged GK interaction preincubated for 20 mins prior to GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0690	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects methylation, decreases expression	6
sodium arsenite	increases expression, decreases expression	3
Tetrachlorodibenzodioxin	increases expression	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	2
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, increases reaction	1
pentanal	decreases expression	1
K 7174	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Aldehydes	decreases expression	1
Azathioprine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Catechin	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases reaction, increases expression, affects cotreatment	1
Metformin	decreases reaction, increases expression	1
Quercetin	increases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
Vanillic Acid	decreases reaction, increases expression	1
Oxyquinoline	increases expression	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1103982	Binding	Activity of glucokinase assessed as stimulatory concentration required to increase 1.5 fold enzymatic activity	Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675). — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00246636	PHASE4	COMPLETED	Evaluation of Efficacy and Safety of Omacor (Omega-3-acid Ethyl Esters) as Add-on Therapy in Hypertriglyceridemic Subjects Treated With Antara (Fenofibrate) Followed by an 8-week Extension
NCT00286234	PHASE4	COMPLETED	Niacin, N-3 Fatty Acids and Insulin Resistance
NCT00346697	PHASE4	COMPLETED	Omega-3 Fatty Acids for High Triglycerides in HIV-infected Patients
NCT00397358	PHASE4	WITHDRAWN	Effect of Extraneal (Icodextrin)on Triglyceride Levels in PD Patients
NCT00473655	PHASE4	COMPLETED	Effect of Rosuvastatin on Triglyceride Levels in Mexican Hypertriglyceridemic Patients
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00745407	PHASE4	COMPLETED	Effects of Fenofibrate on Adipocytokine Levels In Hypertriglyceridemic Patients
NCT00758927	PHASE4	UNKNOWN	The Effects of Omega-3 Fatty Acid (OMACOR) on the Low-density Lipoprotein (LDL) Sub-fraction in Type 2 Diabetic Patients
NCT00891293	PHASE4	COMPLETED	A Second Open-Label Extension of a Double-Blind, Parallel, Phase IV Study to Assess the Efficacy and Safety of Adjunctive Lovaza® (Formerly Known as Omacor®) Therapy in Hypertriglyceridemic Subjects Treated With Antara™
NCT00931879	PHASE4	COMPLETED	Lovaza® and Microvascular Function in Type 2 Diabetes
NCT00934219	PHASE4	UNKNOWN	Triglyceride Lowering Study
NCT01003847	PHASE4	COMPLETED	Differential Metabolic Effects of Fenofibrate and Fatty Acid
NCT01010399	PHASE4	COMPLETED	Boosted Lexiva With Lovaza Adjunctive Therapy in Hypertriglyceridemic, HIV-Infected Subjects
NCT01180764	PHASE4	WITHDRAWN	Effects of Lovaza on High Density Lipoprotein (HDL) Composition and Function in Hypertriglyceridemia
NCT01462877	PHASE4	COMPLETED	A Study to Evaluate Fenofibrate Combination With Statin in Chinese Patients With Dyslipidemic
NCT01480687	PHASE4	UNKNOWN	Fish Oil Supplementation and Vascular Function in Hypertensive Patients With Hypertriglyceridemia
NCT01527747	PHASE4	SUSPENDED	Effects of DPP-4 Inhibition on Triglycerides
NCT01569724	PHASE4	COMPLETED	Carbohydrate Metabolism Disorder Frequency in Hypertriglyceridemia Induced by Bexarotene of Cutaneous T Cell Lymphoma
NCT01625442	PHASE4	COMPLETED	Crocus Sativus (Saffron) and Berberis Vulgaris (Barberry Fruit) in Metabolic Syndrome
NCT01660932	PHASE4	COMPLETED	Vascular and Metabolic Effects of Omega-3 Fatty Acids
NCT01666041	PHASE4	COMPLETED	Vascular and Metabolic Effects of Fenofibrate/Omega vs Fenofibrate
NCT02015988	PHASE4	UNKNOWN	Simvastatin and Fenofibrate vs Simvastatin Alone in Patients With Type 2 Diabetes Mellitus and Acute Coronary Syndrome
NCT02926027	PHASE4	COMPLETED	Effect of Vascepa on Improving Coronary Atherosclerosis in People With High Triglycerides Taking Statin Therapy
NCT03120299	PHASE4	COMPLETED	The Effect of Omega-3 FA on Hypertriglyceridemia in Patients With T2DM(OCEAN)
NCT03342807	PHASE4	UNKNOWN	Intravenous Administration of Insulin and Plasma Exchange on Triglyceride Levels in Early Stage of Hypertriglyceridemia-induced Pancreatitis
NCT03501680	PHASE4	UNKNOWN	Intensive Insulin for Severe/Moderate Hypertriglyceridemia Pancreatitis.
NCT05487833	PHASE4	UNKNOWN	Insulin and Standard Management in Hypertriglyceridemic Acute Pancreatitis
NCT06129526	PHASE4	UNKNOWN	Study of the Efficacy and Safety of EPA in Patients With Type-2 Diabetes
NCT00092560	PHASE3	COMPLETED	Two Investigational Drugs in Patients With Mixed Hyperlipidemia (0653-036)
NCT00092573	PHASE3	COMPLETED	Study of Ezetimibe and Fenofibrate in Patients With Mixed Hyperlipidemia (0653-036)(COMPLETED)
NCT00093899	PHASE3	COMPLETED	A Study to Evaluate an Investigational Drug in Patients With Mixed Hyperlipidemia (0653A-071)(COMPLETED)
NCT00134498	PHASE3	COMPLETED	A Study Comparing The Efficacy & Safety Of Torcetrapib/Atorvastatin And Atorvastatin In Subjects With High Triglycerides
NCT00231621	PHASE3	TERMINATED	A Study on Efficacy and Safety of Topiramate in Treatment of Obese Subjects With Dyslipidemia
NCT00246701	PHASE3	COMPLETED	Evaluation of Efficacy and Safety of Combined Omacor (Omega-3-acid Ethyl Esters) and Simvastatin Therapy in Hypertriglyceridemic Subjects
NCT00435045	PHASE3	COMPLETED	Evaluation of Efficacy and Safety of Omacor, Co-Administered With Atorvastatin, in Subjects With Hypertriglyceridemia
NCT00560430	PHASE3	COMPLETED	Regulation of Inflammatory Parameters by Telmisartan in Hypertensive Patients
NCT00887653	PHASE3	COMPLETED	Changes in Lipids and Safety of Raltegravir in HIV+ Patients With Hyperlipidemia While on Current Standard Therapy
NCT00903409	PHASE3	COMPLETED	Open-Label Extension of a Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Lovaza® and Simvastatin Therapy in Hypertriglyceridemic Subjects
NCT00973271	PHASE3	WITHDRAWN	Diazoxide Choline Controlled-Release Tablet (DCCR) for Very High Triglycerides
NCT01047501	PHASE3	COMPLETED	Effect of AMR101 (Ethyl Icosapentate) on Triglyceride (Tg) Levels in Patients on Statins With High Tg Levels (≥ 200 and < 500 mg/dL)