GSTA4

Summary

GSTA4 (glutathione S-transferase alpha 4, HGNC:4629) is a protein-coding gene on chromosome 6p12.2, encoding Glutathione S-transferase A4 (O15217). Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.

Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson’s disease, Alzheimer’s disease, cataract formation, and atherosclerosis.

Source: NCBI Gene 2941 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 32 total
• Druggable target: yes
• MANE Select transcript: NM_001512

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4629
Approved symbol	GSTA4
Name	glutathione S-transferase alpha 4
Location	6p12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170899
Ensembl biotype	protein_coding
OMIM	605450
Entrez	2941

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000370959, ENST00000370960, ENST00000370963, ENST00000457564, ENST00000477599, ENST00000486559, ENST00000887782, ENST00000887783, ENST00000887784, ENST00000887785, ENST00000887786, ENST00000956299

RefSeq mRNA: 1 — MANE Select: NM_001512 NM_001512

CCDS: CCDS4948

Canonical transcript exons

ENST00000370963 — 7 exons

Exon	Start	End
ENSE00001454017	52995249	52995284
ENSE00003557491	52994157	52994261
ENSE00003618549	52977953	52978592
ENSE00003622297	52985451	52985583
ENSE00003625160	52987357	52987408
ENSE00003647237	52984464	52984605
ENSE00003789084	52982574	52982705

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.4371 / max 454.8522, expressed in 1531 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73981	24.7927	1529
73980	0.3129	150
73982	0.1674	74
73979	0.1642	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.59	gold quality
right adrenal gland	UBERON:0001233	99.51	gold quality
right adrenal gland cortex	UBERON:0035827	99.51	gold quality
adrenal cortex	UBERON:0001235	99.39	gold quality
left adrenal gland	UBERON:0001234	99.38	gold quality
left adrenal gland cortex	UBERON:0035825	99.35	gold quality
cortical plate	UBERON:0005343	99.02	gold quality
ganglionic eminence	UBERON:0004023	98.99	gold quality
adrenal gland	UBERON:0002369	98.98	gold quality
mammalian vulva	UBERON:0000997	98.83	gold quality
upper leg skin	UBERON:0004262	98.61	gold quality
penis	UBERON:0000989	98.15	gold quality
tongue squamous epithelium	UBERON:0006919	97.98	gold quality
cerebellar hemisphere	UBERON:0002245	97.91	gold quality
cerebellar cortex	UBERON:0002129	97.90	gold quality
esophagus squamous epithelium	UBERON:0006920	97.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.76	gold quality
epithelium of esophagus	UBERON:0001976	97.71	gold quality
paraflocculus	UBERON:0005351	97.70	gold quality
middle temporal gyrus	UBERON:0002771	97.69	gold quality
cerebellum	UBERON:0002037	97.66	gold quality
ventricular zone	UBERON:0003053	97.56	gold quality
skin of abdomen	UBERON:0001416	97.51	gold quality
cerebellar vermis	UBERON:0004720	97.38	gold quality
squamous epithelium	UBERON:0006914	97.19	gold quality
gingiva	UBERON:0001828	97.08	gold quality
zone of skin	UBERON:0000014	97.06	gold quality
pituitary gland	UBERON:0000007	97.04	gold quality
embryo	UBERON:0000922	97.02	gold quality
skin of hip	UBERON:0001554	96.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	399.81
E-CURD-114	yes	53.35
E-GEOD-93593	no	11.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting GSTA4, 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-4713-3P	100.00	65.92	505
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-892B	98.00	67.11	821
HSA-MIR-4305	97.94	68.63	533
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-943	97.81	64.42	694
HSA-MIR-4700-3P	97.74	68.64	1014

Literature-anchored findings (GeneRIF, showing 20)

• ability of the two Alpha class subunit interfaces to adopt a functional heterodimeric structure (PMID:11851347)
• expression of hGSTA1/2 and hGSTA4 steady-state mRNAs in second trimester prenatal livers (PMID:12093480)
• null mice had a significantly lower survival time than wild-type controls when chronically treated with relatively low doses of paraquat, a finding consistent with a role of glutathione transferase A4-4 in the defense against oxidative stress (PMID:14761685)
• We now demonstrate that hGSTA4-transfection also causes a profound change in the expression of genes involved in cell adhesion, cell cycle control, proliferation, cell growth, and apoptosis. (PMID:16005854)
• we observed a single nucleotide polymorphism (SNP) G351A leading to the silent mutation Gln117Gln.No significant difference was observed in the distribution of this GSTA4 polymorphism between Parkinson disease individuals and healthy controls (PMID:16054170)
• The effect of over-expression of GSTA4 mRNA on the sensitivity of HepG2 cells to 4-hydroxynonenal injury is reported. (PMID:17553661)
• These results demonstrate that oxidative stress mediated disruption of tight junctions in endothelial cells may be attenuated by hGSTA4-4 expression. (PMID:18080870)
• GSTA4-4 may play an important defensive role against atherogenesis through detoxification of 4-HNE and upregulation of inducible nitric oxide synthase (PMID:18485437)
• genetic polymorphisms in GSTA4 had modification effects on smoking-related lung cancer risk, particularly among patients with squamous cell carcinoma and small-cell-lung-cancer. (PMID:18767114)
• 4-HNE is involved in p53-mediated signaling in in vitro cell cultures as well as in vivo that can be regulated by glutathione transferase (PMID:18930016)
• GSTA4-4 exploits the hydroxyl group of either 4R- or 4S-hydroxynonenal (HNE), while specifically binding HNE and glutathione (GSH) to maintain high catalytic efficiency linked with stereoselective product formation for both enantiomeric substrates. (PMID:20085333)
• Results indicate that downregulation of GSTA4 in adipose tissue leads to increased protein carbonylation, ROS production, and mitochondrial dysfunction and may contribute to the development of insulin resistance and type 2 diabetes. (PMID:20150287)
• analysis of four novel mutations that change the function of leukotriene C(4) synthase and are associated with increased risk of venous thromboembolism and ischemic stroke (PMID:20456754)
• Gsta4/GSTA4 is a novel susceptibility gene for NMSC that affects risk in both mice and humans. (PMID:20966433)
• Data show that mandatory overexpression of hGSTA4 by transient transfection in KYSE30 cells and attenuation of HNE-induced EGFR phosphorylation. (PMID:21751261)
• GSTA4 down-regulation and the concomitant increase in 4-hydroxynonenal adducts in muscle are indicative of susceptibility to infection in individuals with severe thermal injuries. (PMID:22038048)
• 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)
• Data indicate that steroidogenic factor 1 (SF-1) and glutathione S-transferase A (GSTA) family genes (hGSTA1-hGSTA4) are involved in steroidogenesis. (PMID:23650189)
• Decreased gene expression of GSTA4 is associated with drug resistance in cervical cancer. (PMID:24403508)
• These findings demonstrate GSTA4 activation during 4-HNE-induced neoplastic transformation in colorectal carcinogenesis. GSTA4 is a potential surrogate biomarker for CRC screening and should provide novel approaches for chemoprevention. (PMID:27065323)

Cross-species orthologs

41 orthologs

Organism	Symbol	Gene ID
danio_rerio	gstp1.1	ENSDARG00000103019
caenorhabditis_elegans		WBGENE00001749
caenorhabditis_elegans		WBGENE00001750
caenorhabditis_elegans		WBGENE00001751
caenorhabditis_elegans		WBGENE00001752
caenorhabditis_elegans		WBGENE00001753
caenorhabditis_elegans		WBGENE00001754
caenorhabditis_elegans		WBGENE00001755
caenorhabditis_elegans		WBGENE00001756
caenorhabditis_elegans		WBGENE00001757
caenorhabditis_elegans		WBGENE00001758
caenorhabditis_elegans		WBGENE00001759
caenorhabditis_elegans		WBGENE00001760
caenorhabditis_elegans		WBGENE00001761
caenorhabditis_elegans		WBGENE00001762
caenorhabditis_elegans		WBGENE00001764
caenorhabditis_elegans		WBGENE00001765
caenorhabditis_elegans		WBGENE00001766
caenorhabditis_elegans		WBGENE00001767
caenorhabditis_elegans		WBGENE00001769
caenorhabditis_elegans		WBGENE00001770
caenorhabditis_elegans		WBGENE00001771
caenorhabditis_elegans		WBGENE00001772
caenorhabditis_elegans	gst-25	WBGENE00001773
caenorhabditis_elegans		WBGENE00001774
caenorhabditis_elegans		WBGENE00001775
caenorhabditis_elegans		WBGENE00001776
caenorhabditis_elegans		WBGENE00001777
caenorhabditis_elegans		WBGENE00001779
caenorhabditis_elegans		WBGENE00001780
caenorhabditis_elegans		WBGENE00001781
caenorhabditis_elegans		WBGENE00001782
caenorhabditis_elegans		WBGENE00001783
caenorhabditis_elegans		WBGENE00001785
caenorhabditis_elegans		WBGENE00001786
caenorhabditis_elegans		WBGENE00001787
caenorhabditis_elegans		WBGENE00001789
caenorhabditis_elegans		WBGENE00018911
caenorhabditis_elegans		WBGENE00018912
caenorhabditis_elegans	W10C8.4	WBGENE00021127
caenorhabditis_elegans		WBGENE00021566

Paralogs (11): GSTP1 (ENSG00000084207), GSTM1 (ENSG00000134184), GSTM5 (ENSG00000134201), GSTM3 (ENSG00000134202), HPGDS (ENSG00000163106), GSTM4 (ENSG00000168765), GSTA3 (ENSG00000174156), GSTA5 (ENSG00000182793), GSTM2 (ENSG00000213366), GSTA1 (ENSG00000243955), GSTA2 (ENSG00000244067)

Protein

Protein identifiers

Glutathione S-transferase A4 — O15217 (reviewed: O15217)

Alternative names: GST class-alpha member 4, Glutathione S-transferase A4-4

All UniProt accessions (2): O15217, Q5JW88

UniProt curated annotations — full annotation on UniProt →

Function. Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4-hydroxynonenal (4-HNE).

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed at a high level in brain, placenta, and skeletal muscle and much lower in lung and liver.

Similarity. Belongs to the GST superfamily. Alpha family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15217-1	1	yes
O15217-2	2

RefSeq proteins (1): NP_001503* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003080	GST_alpha	Family
IPR004045	Glutathione_S-Trfase_N	Domain
IPR004046	GST_C	Domain
IPR010987	Glutathione-S-Trfase_C-like	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR036282	Glutathione-S-Trfase_C_sf	Homologous_superfamily
IPR040079	Glutathione_S-Trfase	Family
IPR050213	GST_superfamily	Family

Pfam: PF02798, PF14497

Enzyme classification (BRENDA):

• EC 2.5.1.18 — glutathione transferase (BRENDA: 178 organisms, 548 substrates, 680 inhibitors, 878 Km, 525 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
1-CHLORO-2,4-DINITROBENZENE	0.0003–223.6	289
GLUTATHIONE	0.0002–532.43	253
GSH	0.0003–37.4	62
REDUCED GLUTATHIONE	0.017–11.4	24
ETHACRYNIC ACID	0.0001–2.43	19
CUMENE HYDROPEROXIDE	0.038–14.3	10
(+)-2-BROMO-3-(4-NITROPHENYL)PROPANOIC ACID	0.023–0.417	8
MONOCHLOROBIMANE	0.004–0.25	8
4-CHLORO-7-NITROBENZO-2-OXA-1,3-DIAZOLE	0.324–3.866	7
1-IODOHEXANE	0.009–0.059	6
ALACHLOR	0.042–7.23	6
PHENETHYL ISOTHIOCYANATE	0.0065–0.14	6
STYRENE 7,8-OXIDE	0.064–0.365	6
1,2-DICHLORO-4-NITROBENZENE	0.27–1.4	5
1-CHLORO-2,3-DINITROBENZOATE	0.21–20.7	5

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (32 total): helix 11, strand 6, binding site 4, domain 2, sequence variant 2, mutagenesis site 2, turn 2, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3IK7	X-RAY DIFFRACTION	1.97
1GUL	X-RAY DIFFRACTION	2.7
1GUM	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15217-F1	97.10	0.97

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): 9; 54–55; 67–68; 212

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (2):

Position	Phenotype
9	reduces catalytic activity 70-fold.
212	strongly reduced activity towards 4-hydroxynon-2-enal and 1-chloro-2,4-dinitrobenzene.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-156590	Glutathione conjugation

MSigDB gene sets: 203 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, CHANDRAN_METASTASIS_DN, LEE_LIVER_CANCER_CIPROFIBRATE_DN, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, WEINMANN_ADAPTATION_TO_HYPOXIA_UP, PATIL_LIVER_CANCER, MODULE_66, MAHAJAN_RESPONSE_TO_IL1A_DN, KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_UP, chr6p12, GOBP_AMIDE_METABOLIC_PROCESS, ONDER_CDH1_TARGETS_2_UP, WANG_CISPLATIN_RESPONSE_AND_XPC_DN

GO Biological Process (2): glutathione metabolic process (GO:0006749), xenobiotic metabolic process (GO:0006805)

GO Molecular Function (5): glutathione transferase activity (GO:0004364), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
modified amino acid metabolic process	1
sulfur compound metabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSTA4	SLCO6A1	Q86UG4	790
GSTA4	GSTM1	P09488	675
GSTA4	GSTM2	P28161	672
GSTA4	GSTM3	P21266	659
GSTA4	GSTT2B	P0CG30	652
GSTA4	GSTO1	P78417	637
GSTA4	HSPA4	P34932	616
GSTA4	GCLC	P48506	612
GSTA4	GSTM4	Q03013	611
GSTA4	GCLM	P48507	550
GSTA4	GSTK1	Q9Y2Q3	531
GSTA4	ACVR1	Q04771	529
GSTA4	GPX3	P22352	523
GSTA4	NQO1	P15559	513
GSTA4	CILK1	Q9UPZ9	499

IntAct

54 interactions, top by confidence:

A	B	Type	Score
GSTA2	GSTA4	psi-mi:“MI:0915”(physical association)	0.920
GSTA2	GSTA4	psi-mi:“MI:0914”(association)	0.920
GSTA4	GSTA2	psi-mi:“MI:0915”(physical association)	0.920
GSTA4	GSTA4	psi-mi:“MI:0915”(physical association)	0.740
GSTA4	CIMIP5	psi-mi:“MI:0915”(physical association)	0.720
CIMIP5	GSTA4	psi-mi:“MI:0915”(physical association)	0.720
DAL2	GSTA4	psi-mi:“MI:0915”(physical association)	0.560
GCD7	GSTA4	psi-mi:“MI:0915”(physical association)	0.560
GSTA4	TAE1	psi-mi:“MI:0915”(physical association)	0.560
TAE1	GSTA4	psi-mi:“MI:0915”(physical association)	0.560
GSTA4	GAS8	psi-mi:“MI:0915”(physical association)	0.560
LSM1	GSTA4	psi-mi:“MI:0915”(physical association)	0.560
GSTA4	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (26): GSTA4 (Two-hybrid), GSTA4 (Two-hybrid), C2orf50 (Two-hybrid), GSTA4 (Affinity Capture-MS), GSTA4 (Affinity Capture-MS), GSTA4 (Two-hybrid), GSTA4 (Co-fractionation), GSTA4 (Two-hybrid), GSTA4 (Affinity Capture-MS), GSTA4 (Affinity Capture-MS), GSTA4 (Affinity Capture-MS), GSTA4 (Two-hybrid), GSTA4 (Two-hybrid), GSTA4 (Two-hybrid), GSTA4 (Two-hybrid)

ESM2 similar proteins: A0A1U8QXK4, A0A1U9YI21, A4GYZ0, A8XT16, B5BP46, B8NM79, C8VQ63, F4IA73, M1W426, O15217, O74830, P21161, P30113, P30114, P30347, P34277, P34345, P42936, P43387, P46417, P46421, P46429, P50471, Q00717, Q2UPB2, Q54UR0, Q54VI4, Q55FF3, Q5E9G0, Q6AXY0, Q6NMS0, Q6Q882, Q86AU1, Q8SSU2, Q9C8M3, Q9CA57, Q9CAS6, Q9FG59, Q9FUS6, Q9FUS9

Diamond homologs: O15217, O18879, O73888, P00502, P04903, P04904, P04906, P08263, P09210, P09211, P10648, P13745, P14942, P19157, P24472, P26624, P26697, P30115, P35661, P46088, P46418, P46424, P46425, P47954, P51781, P80031, P80894, P81706, P81942, Q08392, Q08393, Q08862, Q08863, Q16772, Q28035, Q28514, Q54YN2, Q556G3, Q5E9G0, Q5R8R5

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PKC	“up-regulates activity”	GSTA4	phosphorylation
PKA	“up-regulates activity”	GSTA4	phosphorylation
ROS	up-regulates	GSTA4
HSPA1A	“up-regulates activity”	GSTA4	relocalization
HSPA1B	“up-regulates activity”	GSTA4	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1024 predictions. Top by Δscore:

Variant	Effect	Δscore
6:52984519:T:TA	donor_gain	1.0000
6:52984520:C:A	donor_gain	1.0000
6:52985449:A:AC	donor_gain	1.0000
6:52985450:C:CC	donor_gain	1.0000
6:52987405:CAAA:C	acceptor_gain	1.0000
6:52987409:C:CC	acceptor_gain	1.0000
6:52978590:TTCC:T	acceptor_loss	0.9900
6:52978591:TCC:T	acceptor_loss	0.9900
6:52978592:CCT:C	acceptor_loss	0.9900
6:52978593:C:CA	acceptor_loss	0.9900
6:52978594:T:G	acceptor_loss	0.9900
6:52984492:ATAG:A	donor_gain	0.9900
6:52984605:CCT:C	acceptor_gain	0.9900
6:52984607:T:C	acceptor_gain	0.9900
6:52985442:C:CT	donor_gain	0.9900
6:52985460:T:TA	donor_gain	0.9900
6:52985461:C:CA	donor_gain	0.9900
6:52978593:C:CC	acceptor_gain	0.9800
6:52978595:G:C	acceptor_loss	0.9800
6:52984457:CACCT:C	donor_loss	0.9800
6:52984458:ACCTA:A	donor_loss	0.9800
6:52984459:CCTA:C	donor_loss	0.9800
6:52984460:CT:C	donor_loss	0.9800
6:52984461:TAC:T	donor_loss	0.9800
6:52984462:A:AG	donor_loss	0.9800
6:52984463:CCTTT:C	donor_loss	0.9800
6:52984604:TCCT:T	acceptor_loss	0.9800
6:52984605:CCTTA:C	acceptor_loss	0.9800
6:52984606:CTTAA:C	acceptor_loss	0.9800
6:52984607:T:G	acceptor_loss	0.9800

AlphaMissense

1471 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:52987406:A:C	F30L	0.993
6:52987406:A:T	F30L	0.993
6:52987408:A:G	F30L	0.993
6:52994183:A:G	W21R	0.990
6:52994183:A:T	W21R	0.990
6:52985567:G:C	F52L	0.988
6:52985567:G:T	F52L	0.988
6:52985569:A:G	F52L	0.988
6:52984586:C:A	G98W	0.987
6:52978548:G:C	F197L	0.985
6:52978548:G:T	F197L	0.985
6:52978550:A:G	F197L	0.985
6:52985496:G:T	A76E	0.985
6:52985497:C:G	A76P	0.984
6:52985513:G:C	S70R	0.983
6:52985513:G:T	S70R	0.983
6:52985515:T:G	S70R	0.983
6:52985550:A:T	V58D	0.983
6:52994184:T:A	R20S	0.981
6:52994184:T:G	R20S	0.981
6:52982658:G:C	S154R	0.979
6:52982658:G:T	S154R	0.979
6:52982660:T:G	S154R	0.979
6:52984586:C:G	G98R	0.977
6:52984586:C:T	G98R	0.977
6:52985556:G:T	P56H	0.977
6:52994195:C:T	E17K	0.977
6:52982650:T:A	D157V	0.976
6:52985569:A:T	F52I	0.976
6:52994185:C:G	R20T	0.976

dbSNP variants (sampled 300 via entrez): RS1000210850 (6:52994666 A>C,T), RS1000360756 (6:52995937 G>A,T), RS1000576131 (6:52979320 A>T), RS1000600490 (6:52984005 C>G,T), RS1000728494 (6:52977506 C>T), RS1000885244 (6:52996159 T>G), RS1001076659 (6:52984401 T>C,G), RS1001152672 (6:52992710 T>C), RS1001172400 (6:52993837 C>T), RS1001199390 (6:52979638 T>C), RS1001297767 (6:52987271 C>A), RS1001452121 (6:52980492 TGG>T), RS1001635428 (6:52987622 G>T), RS1001916339 (6:52980727 G>C), RS1002126456 (6:52994698 T>A)

Disease associations

OMIM: gene MIM:605450 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002141_5	Epilepsy (remission after treatment)	2.000000e-07
GCST003181_5	Staphylococcus aureus nasal carriage (intermittent)	9.000000e-06
GCST003999_19	Nose size	2.000000e-07
GCST008403_23	Arterial stiffness index	9.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007758	intermittent Staphylococcus aureus carrier status
EFO:0004517	arterial stiffness measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4933 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
4-hydroxy-2-nonenal	affects binding, affects metabolic processing	9
Tobacco Smoke Pollution	affects expression, decreases expression, decreases methylation, increases expression	5
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	3
Cyclosporine	decreases expression	3
arsenite	affects expression, increases methylation	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
8-isoprostaglandin A2	affects metabolic processing, decreases activity	2
Acetaminophen	decreases expression, affects cotreatment	2
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Butyrates	increases expression	2
Cisplatin	increases expression, affects expression, affects cotreatment	2
Doxorubicin	affects response to substance, decreases expression	2
Glutathione	affects cotreatment, increases metabolic processing, affects metabolic processing	2
Valproic Acid	affects expression, decreases expression	2
tert-Butylhydroperoxide	decreases expression	2
abemaciclib	increases expression	1
dicrotophos	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
methylmercuric chloride	decreases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, increases expression	1
bisphenol A	affects expression	1
senecionine	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
2-chloroethyl ethyl sulfide	decreases expression	1
4-hydroxy-2-decenal	affects metabolic processing	1
epigallocatechin gallate	affects cotreatment, decreases expression	1

ChEMBL screening assays

10 unique, capped per target: 9 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743225	ADMET	Substrates for human cytosolic glutathione transferase GSTA4	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition
CHEMBL5551052	Binding	Substrate activity at N-terminal His6 tagged human GSTA4-4 expressed in Escherichia coli BL21(DE3) assessed as catalytic constant at pH 6.5 at 30 degreeC by Michaelis-Menten analysis	Human mitochondrial glutathione transferases: Kinetic parameters and accommodation of a mitochondria-targeting group in substrates. — Bioorg Med Chem

Clinical trials (associated diseases)

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