GSTK1

Summary

GSTK1 (glutathione S-transferase kappa 1, HGNC:16906) is a protein-coding gene on chromosome 7q34, encoding Glutathione S-transferase kappa 1 (Q9Y2Q3). Glutathione S-transferase that catalyzes the conjugation of glutathione to exogenous and endogenous compounds.

This gene encodes a member of the kappa class of the glutathione transferase superfamily of enzymes that function in cellular detoxification. The encoded protein is localized to the peroxisome and catalyzes the conjugation of glutathione to a wide range of hydrophobic substates facilitating the removal of these compounds from cells. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 373156 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 55 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015917

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16906
Approved symbol	GSTK1
Name	glutathione S-transferase kappa 1
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	GST13
Ensembl gene	ENSG00000197448
Ensembl biotype	protein_coding
OMIM	602321
Entrez	373156

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000358406, ENST00000409500, ENST00000436038, ENST00000442394, ENST00000443571, ENST00000473649, ENST00000479303, ENST00000489654, ENST00000494735, ENST00000881233, ENST00000881234, ENST00000881235, ENST00000881236, ENST00000881237, ENST00000881238, ENST00000881239, ENST00000881240, ENST00000881241, ENST00000881242, ENST00000911357, ENST00000968445, ENST00000968446, ENST00000968447

RefSeq mRNA: 4 — MANE Select: NM_015917 NM_001143679, NM_001143680, NM_001143681, NM_015917

CCDS: CCDS47730, CCDS47731, CCDS47732, CCDS5877

Canonical transcript exons

ENST00000358406 — 8 exons

Exon	Start	End
ENSE00001917147	143268788	143269115
ENSE00002030797	143263441	143263585
ENSE00002119390	143264548	143264676
ENSE00003469052	143265261	143265296
ENSE00003511358	143267617	143267733
ENSE00003553250	143268091	143268184
ENSE00003564325	143264086	143264167
ENSE00003789526	143264992	143265092

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 112.2274 / max 962.3726, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81758	80.7832	1824
81757	31.4191	1821
81759	0.0251	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.38	gold quality
apex of heart	UBERON:0002098	99.30	gold quality
mucosa of transverse colon	UBERON:0004991	99.19	gold quality
right lobe of liver	UBERON:0001114	99.08	gold quality
rectum	UBERON:0001052	99.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.00	gold quality
monocyte	CL:0000576	98.98	gold quality
metanephros cortex	UBERON:0010533	98.98	gold quality
leukocyte	CL:0000738	98.91	gold quality
mononuclear cell	CL:0000842	98.90	gold quality
right adrenal gland cortex	UBERON:0035827	98.89	gold quality
transverse colon	UBERON:0001157	98.86	gold quality
right adrenal gland	UBERON:0001233	98.85	gold quality
right uterine tube	UBERON:0001302	98.80	gold quality
right lobe of thyroid gland	UBERON:0001119	98.78	gold quality
left lobe of thyroid gland	UBERON:0001120	98.78	gold quality
gall bladder	UBERON:0002110	98.77	gold quality
small intestine	UBERON:0002108	98.70	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.70	gold quality
minor salivary gland	UBERON:0001830	98.68	gold quality
spleen	UBERON:0002106	98.68	gold quality
right atrium auricular region	UBERON:0006631	98.66	gold quality
left adrenal gland	UBERON:0001234	98.64	gold quality
left adrenal gland cortex	UBERON:0035825	98.60	gold quality
thyroid gland	UBERON:0002046	98.56	gold quality
body of stomach	UBERON:0001161	98.42	gold quality
adrenal cortex	UBERON:0001235	98.42	gold quality
tibial nerve	UBERON:0001323	98.42	gold quality
heart left ventricle	UBERON:0002084	98.42	gold quality
lymph node	UBERON:0000029	98.41	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	88.61
E-CURD-122	yes	59.64
E-GEOD-125970	yes	7.80
E-MTAB-10042	yes	7.78
E-MTAB-7606	no	3449.21
E-CURD-97	no	1157.88
E-MTAB-8911	no	994.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CUX1, ESR1, FOS, HNF1A, IRF6, JUN, JUNB, JUND, MAF, NFE2L2, NR1H4, SP1, SP3, STAT1, TP53

miRNA regulators (miRDB)

23 targeting GSTK1, 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-4283	100.00	66.42	2097
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-515-3P	97.92	67.98	506
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-4642	97.52	67.60	916
HSA-MIR-505-5P	97.01	65.54	778
HSA-MIR-656-5P	96.82	67.67	372
HSA-MIR-875-5P	96.74	66.48	579
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-8071	95.69	64.93	484
HSA-LET-7D-3P	89.01	66.89	93

Literature-anchored findings (GeneRIF, showing 28)

• structure and function characterization of a GST from human breast (PMID:14709161)
• Gene and protein characterization; its subcellular localization in peroxisomes, suggesting a new function for this family of enzymes [glutathione S-transferase kappa (hGSTK1)] (PMID:14742434)
• Presence of hGSTK1 in both peroxisomes and mitochondria. The C-terminus of hGSTK1 is essential for localization of the protein to peroxisomes, and the C-terminal sequence Ala-Arg-Leu represents a peroxisome targeting signal 1 (PTS1). (PMID:14742434)
• crystal structure of hGSTK1 has been determined by the multiple-isomorphous replacement method and refined to 1.93 A resolution (PMID:16081649)
• Our results suggest that genetic polymorphisms of xenobiotic-metabolizing enzymes could play an important role in infertility. (PMID:18774560)
• SNP-1308G/T (rs1917760) genotypes of DsbA-L gene might participate in insulin secretion and body fat distribution. It is possible that polymorphisms of DsbA-L gene associated with metabolic diseases[DsbA-L] (PMID:19225211)
• The objective of this study was to investigate the molecular mechanisms underlying Group B Streptococcus-human umbilical vein endothelial cells interaction, focusing specifically on the responsiveness of host protein tyrosine kinase (PTK). (PMID:19639233)
• This study does not give evidence of interaction between the GST polymorphisms and smoking may although this study provided sufficient statistical power to detect modest interaction. (PMID:20472488)
• drug resistance in three strains of tumor cells is associated with significant increase in hGSTP1 and hGSTA4 gene expression, whereas increased hGSTK1 gene expression was detected only in resistant erythroleukemia and mammary adenocarcinoma cells. (PMID:23330092)
• we have optimized the GST-Nck1-SH2 pull-down procedure to obtain tyrosine-phosphorylated proteins in tumor tissues (PMID:23426619)
• DsbA-L is localized in both the mitochondria and the endoplasmic reticulum (ER) in adipocytes; its ER localization plays a critical role in suppressing ER stress and promoting adiponectin biosynthesis and secretion. (PMID:25739441)
• GSTK1 T/T genotype may be a novel risk factor for the prediction of overweight status in SCZ male patients. (PMID:27010189)
• we confirmed several existing chemoinformatic filters and more importantly extended them as well as added novel filters that specify compounds with anti-GST/GSH activity. Selected compounds were also tested using different antibody-based GST detection technologies and exhibited no interference clearly demonstrating specificity toward their GST/GSH interaction. (PMID:27044684)
• High glutathione-S-transferase is associated with type 2 diabetes mellitus. (PMID:27377684)
• Our findings indicate that the medical staff exposed to low IR levels were under risk of significant oxidative stress that was enhanced by their glutathione S-transferase (GST) polymorphisms. (PMID:28287017)
• Several biological properties of the GST-hNdCTR1 fusion protein were assessed. It was demonstrated that in cells, the protein was prone to oligomerization, formed inclusion bodies and displayed no toxicity. Treatment of E. coli cells with copper and silver ions reduced cell viability in a dose- and time-dependent manner (PMID:29099786)
• The population prediction model of BMI indicated that the DsbA-L T/T genotype was significantly associated with a high BMI. The BMI-based NAFLD prediction model showed that the DsbA-L T/T genotype did not have any direct impact on the risk of NAFLD, whereas the structural equation model suggested that this genotype might be indirectly or partially associated with NAFLD risk through a high BMI and low adiponectin. (PMID:29569850)
• No convincing evidence that the GST genotypes studied are related to asthma outcomes. (PMID:29785881)
• It is a key molecule in multimerization and activation of adiponectin. (PMID:30606929)
• DsbA-L plays a critical protective role in renal ectopic fat deposition and lipid-related kidney injury in mice with diabetic nephropathy (DN) and patients with DN. The mechanisms might involve the inhibition of cholesterol synthesis through the inactivation of HMGCR and the promotion of lipolysis through the activation of ATGL and the subsequent reduction of lipid droplets accumulation in the kidney. (PMID:30791996)
• Plasma mtDNA copy numbers are associated with GSTK1 expression and inflammation in type 2 diabetes. (PMID:31502701)
• DsbA-L modifies mtROS/JNK/MFF-related mitochondrial fission, linking alterations in mitochondrial dynamics during tubular injury in the pathogenesis of diabetic kidney disease. (PMID:32167139)
• The DsbA-L gene is associated with respiratory function of the elderly via its adiponectin multimeric or antioxidant properties. (PMID:32249844)
• DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice. (PMID:32948751)
• T cell metabolism in obesity and beyond: comments on ‘DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-gamma production’. (PMID:33538302)
• Silencing of DsbA-L gene impairs the PPARgamma agonist function of improving insulin resistance in a high-glucose cell model. (PMID:33843164)
• [Multifaceted Clinical Research on Obesity-related Disease Prevention Focusing on the DsbA-L Gene]. (PMID:36328447)
• New insights of DsbA-L in the pathogenesis of metabolic diseases. (PMID:38430301)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	gstk2	ENSDARG00000019585
danio_rerio	gstk1	ENSDARG00000056510
danio_rerio	gstk4	ENSDARG00000092052
danio_rerio	si:dkey-40m6.14	ENSDARG00000093119
danio_rerio		ENSDARG00000110055
mus_musculus	Gstk1	ENSMUSG00000029864
rattus_norvegicus	Gstk1	ENSRNOG00000016484
caenorhabditis_elegans		WBGENE00014251
caenorhabditis_elegans		WBGENE00017054

Protein

Protein identifiers

Glutathione S-transferase kappa 1 — Q9Y2Q3 (reviewed: Q9Y2Q3)

Alternative names: GST 13-13, GST class-kappa, GSTK1-1, Glutathione S-transferase subunit 13

All UniProt accessions (4): C9JNT3, E9PFN5, Q9Y2Q3, Q6FII1

UniProt curated annotations — full annotation on UniProt →

Function. Glutathione S-transferase that catalyzes the conjugation of glutathione to exogenous and endogenous compounds. Significant glutathione conjugating activity is found only with the model substrate, 1-chloro-2,4-dinitrobenzene (CDNB).

Subunit / interactions. Homodimer.

Subcellular location. Peroxisome.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the GST superfamily. Kappa family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9Y2Q3-1	1	yes
Q9Y2Q3-2	2
Q9Y2Q3-3	3
Q9Y2Q3-4	4

RefSeq proteins (4): NP_001137151, NP_001137152, NP_001137153, NP_057001* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001853	DSBA-like_thioredoxin_dom	Domain
IPR014440	HCCAis_GSTk	Family
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR044088	GSTK	Family
IPR051924	GST_Kappa/NadH	Family

Pfam: PF01323

Catalyzed reactions (Rhea), 1 shown:

• RX + glutathione = an S-substituted glutathione + a halide anion + H(+) (RHEA:16437)

UniProt features (42 total): helix 11, modified residue 10, strand 6, sequence conflict 5, binding site 4, splice variant 3, turn 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3RPP	X-RAY DIFFRACTION	1.8
3RPN	X-RAY DIFFRACTION	1.9
1YZX	X-RAY DIFFRACTION	1.93

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2Q3-F1	95.57	0.92

Functional residue map

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

Ligand- & substrate-binding residues (4): 16–18; 53; 183; 200–201

Post-translational modifications (10): 144, 158, 158, 165, 169, 49, 71, 85, 116, 116

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-156590	Glutathione conjugation
R-HSA-9033241	Peroxisomal protein import

MSigDB gene sets: 204 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_BIOLOGICAL_OXIDATIONS, SAENZ_DETOX_PATHWAY_AND_CARCINOGENESIS_DN, HEIDENBLAD_AMPLICON_8Q24_DN, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, KESHELAVA_MULTIPLE_DRUG_RESISTANCE, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_DETOXIFICATION, SANSOM_APC_TARGETS_DN, REACTOME_GLUTATHIONE_CONJUGATION, GUO_HEX_TARGETS_DN, GOBP_GLUTATHIONE_METABOLIC_PROCESS

GO Biological Process (3): glutathione metabolic process (GO:0006749), epithelial cell differentiation (GO:0030855), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (5): glutathione transferase activity (GO:0004364), glutathione peroxidase activity (GO:0004602), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), transferase activity (GO:0016740)

GO Cellular Component (8): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), membrane (GO:0016020), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
catalytic activity	2
cytoplasm	2
modified amino acid metabolic process	1
sulfur compound metabolic process	1
cell differentiation	1
epithelium development	1
cellular detoxification	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
peroxidase activity	1
binding	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
microbody	1
peroxisome	1
microbody lumen	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1706 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSTK1	HPGDS	O60760	948
GSTK1	GSTO2	Q9H4Y5	752
GSTK1	GSTP1	P09211	749
GSTK1	GSTT2B	P0CG30	747
GSTK1	GSTO1	P78417	699
GSTK1	GSTZ1	O43708	645
GSTK1	GSTM1	P09488	564
GSTK1	MGST1	P10620	564
GSTK1	CYP1B1	Q16678	544
GSTK1	GSTM2	P28161	540
GSTK1	GSTM3	P21266	540
GSTK1	GSTM4	Q03013	538
GSTK1	GSTA4	O15217	531
GSTK1	MGST2	Q99735	515
GSTK1	CYP1A1	P04798	511

IntAct

173 interactions, top by confidence:

A	B	Type	Score
PPP2R2D	YEATS4	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GSTK1	FAM9B	psi-mi:“MI:0915”(physical association)	0.670
FAM9B	GSTK1	psi-mi:“MI:0915”(physical association)	0.670
ASPH	STXBP3	psi-mi:“MI:0914”(association)	0.640
OSER1	LACC1	psi-mi:“MI:0914”(association)	0.620
Adipoq	GSTK1	psi-mi:“MI:0407”(direct interaction)	0.570
CCNDBP1	GSTK1	psi-mi:“MI:0915”(physical association)	0.560
GSTK1	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.560
GSTK1	TK2	psi-mi:“MI:0914”(association)	0.560
TK2	GSTK1	psi-mi:“MI:0915”(physical association)	0.560
HIRA	CSPG5	psi-mi:“MI:0914”(association)	0.530
DCAF11	COPS2	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
PIP4K2A	GSTK1	psi-mi:“MI:0915”(physical association)	0.370
PRPF19	GSTK1	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
COQ9	ACOT7	psi-mi:“MI:0914”(association)	0.350
PEX5	AGPS	psi-mi:“MI:0914”(association)	0.350
CENPM	DNM1L	psi-mi:“MI:0914”(association)	0.350

BioGRID (137): GSTK1 (Two-hybrid), GSTK1 (Two-hybrid), GSTK1 (Two-hybrid), GSTK1 (Affinity Capture-MS), GSTK1 (Affinity Capture-MS), GSTK1 (Affinity Capture-MS), CYCS (Co-fractionation), GSTK1 (Co-fractionation), GSTK1 (Co-fractionation), GSTK1 (Co-fractionation), GSTK1 (Proximity Label-MS), GSTK1 (Affinity Capture-MS), GSTK1 (Affinity Capture-MS), TK2 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS)

ESM2 similar proteins: A4FUF0, A5HK05, B0K012, O43324, O43929, O75431, O94955, O95453, P20135, P42694, P47802, P69341, P70102, P78417, Q2L969, Q3U2J5, Q3UFS0, Q49A26, Q4R8V9, Q562D5, Q5R6Z7, Q5R7T2, Q5RC51, Q5RDU9, Q5RKH0, Q5ZIA0, Q5ZLS2, Q5ZLS7, Q6AXV9, Q6DC64, Q6DFV5, Q6GR37, Q6NYU2, Q7SXV1, Q7Z624, Q8IX04, Q8K2D3, Q8K2Q2, Q8R5L3, Q8VE33

Diamond homologs: P24473, Q09652, Q9DCM2, Q9Y2Q3, Q18973, Q51948, Q52462, Q9X9Q7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 179 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 3’-end processing	6	9.4×	6e-03
mRNA Polyadenylation	10	7.0×	6e-04
Processing of Capped Intron-Containing Pre-mRNA	9	5.9×	4e-03
mRNA Splicing - Major Pathway	12	5.2×	8e-04
Dengue Virus-Host Interactions	14	5.1×	5e-04
Metabolism of RNA	12	4.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1196 predictions. Top by Δscore:

Variant	Effect	Δscore
7:143264165:GTG:G	donor_gain	1.0000
7:143264991:GGAA:G	acceptor_gain	1.0000
7:143265090:AGG:A	donor_gain	1.0000
7:143265091:GG:G	donor_gain	1.0000
7:143265091:GGG:G	donor_gain	1.0000
7:143265091:GGGTG:G	donor_loss	1.0000
7:143265092:GG:G	donor_gain	1.0000
7:143265092:GGTG:G	donor_loss	1.0000
7:143265093:G:GA	donor_loss	1.0000
7:143265093:G:GG	donor_gain	1.0000
7:143265094:T:G	donor_loss	1.0000
7:143265297:G:GG	donor_gain	1.0000
7:143267727:A:G	donor_gain	1.0000
7:143267734:G:GG	donor_gain	1.0000
7:143267794:C:G	donor_gain	1.0000
7:143268071:A:AG	acceptor_gain	1.0000
7:143268071:ATT:A	acceptor_gain	1.0000
7:143268072:T:G	acceptor_gain	1.0000
7:143263550:G:GT	donor_gain	0.9900
7:143263581:TCGAG:T	donor_loss	0.9900
7:143263582:CGAGG:C	donor_loss	0.9900
7:143263583:GAGGT:G	donor_loss	0.9900
7:143263584:AGGTG:A	donor_loss	0.9900
7:143263585:GGTGA:G	donor_loss	0.9900
7:143263586:G:GA	donor_loss	0.9900
7:143263587:T:A	donor_loss	0.9900
7:143263621:G:GT	donor_gain	0.9900
7:143263621:G:T	donor_gain	0.9900
7:143264150:G:GT	donor_gain	0.9900
7:143264151:G:T	donor_gain	0.9900

AlphaMissense

1474 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:143268094:T:C	F181L	0.992
7:143268096:T:A	F181L	0.992
7:143268096:T:G	F181L	0.992
7:143268145:T:C	F198L	0.990
7:143268147:T:A	F198L	0.990
7:143268147:T:G	F198L	0.990
7:143264137:A:C	S42R	0.981
7:143264139:C:A	S42R	0.981
7:143264139:C:G	S42R	0.981
7:143263551:A:T	D13V	0.980
7:143263580:T:C	F23L	0.980
7:143263582:C:A	F23L	0.980
7:143263582:C:G	F23L	0.980
7:143268158:G:C	R202P	0.980
7:143264579:A:C	K62N	0.979
7:143264579:A:T	K62N	0.979
7:143265084:T:A	W126R	0.979
7:143265084:T:C	W126R	0.979
7:143264994:A:C	S96R	0.977
7:143264996:T:A	S96R	0.977
7:143264996:T:G	S96R	0.977
7:143265072:T:A	W122R	0.976
7:143265072:T:C	W122R	0.976
7:143263544:T:C	F11L	0.975
7:143263546:C:A	F11L	0.975
7:143263546:C:G	F11L	0.975
7:143265013:T:C	F102S	0.971
7:143265061:C:T	S118F	0.970
7:143265064:G:C	R119P	0.970
7:143263569:C:T	S19F	0.969

dbSNP variants (sampled 300 via entrez): RS1000713105 (7:143266900 A>C,G), RS1000774384 (7:143268427 A>G), RS1000965458 (7:143263847 A>T), RS1001227212 (7:143266725 G>A,T), RS1001243115 (7:143262857 G>A), RS1001695757 (7:143262580 T>C), RS1001724369 (7:143263171 C>T), RS1001763310 (7:143269148 C>T), RS1002063017 (7:143264444 GAA>G,GA,GAAA,GAAAA), RS1002198839 (7:143264874 C>G,T), RS1002535810 (7:143266606 C>T), RS1002716850 (7:143263843 G>A), RS1004512742 (7:143264379 G>A), RS1004690753 (7:143269275 C>T), RS1005115162 (7:143263768 C>A,T)

Disease associations

OMIM: gene MIM:602321 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4491 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 300,503 (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
CHEMBL1543	GLUTATHIONE	3	300,503

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.70	IC50	20	nM	GLUTATHIONE
5.28	IC50	5200	nM	CHEMBL75497
5.16	Kd	6958	nM	CHEMBL3752910
5.16	ED50	6958	nM	CHEMBL3752910
5.00	IC50	1.01e+04	nM	CHEMBL73552

PubChem BioAssay actives

3 with measured affinity, of 81 total; 3 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
Glutathione	75134: Affinity towards recombinant Glutathione S-transferase (GST) Enzyme.	ic50	0.0200	uM
5-(sulfanylmethyl)undecanedioic acid	75134: Affinity towards recombinant Glutathione S-transferase (GST) Enzyme.	ic50	5.2000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149864: Binding affinity to human GSTK1 incubated for 45 mins by Kinobead based pull down assay	kd	6.9584	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects cotreatment, decreases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	affects expression, decreases expression, increases abundance	3
cobaltous chloride	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
GSK-J4	decreases expression	1
4-((alpha-L-rhamnosyloxy)benzyl)isothiocyanate	decreases expression, decreases reaction	1
bismuth tripotassium dicitrate	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
apocarotenal	decreases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
beta-lapachone	increases expression, decreases expression	1
bleomycetin	decreases expression	1
dinophysistoxin 1	decreases expression	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Bilirubin	decreases expression	1
Chenodeoxycholic Acid	affects cotreatment, decreases expression	1

ChEMBL screening assays

27 unique, capped per target: 13 binding, 12 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743226	ADMET	Substrates for human mitochondrial glutathione transferase GSTK1	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition
CHEMBL4118629	Binding	Binding affinity to GSTK1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem
CHEMBL683576	Functional	Induction of increased cytosolic glutathione S-transferase activity in bladder of A/J mice treated with 3 doses of 0.04 mM compound (dissolved in 0.3 mL of cottonseed oil) for 2 days	Phenylalkyl isothiocyanate-cysteine conjugates as glutathione S-transferase stimulating agents. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2YC	Abcam HEK293T GSTK1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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