GSTM4

Summary

GSTM4 (glutathione S-transferase mu 4, HGNC:4636) is a protein-coding gene on chromosome 1p13.3, encoding Glutathione S-transferase Mu 4 (Q03013). 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. 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-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual’s susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. Multiple transcript variants, each encoding a distinct protein isoform, have been identified.

Source: NCBI Gene 2948 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 57 total
• Druggable target: yes
• MANE Select transcript: NM_000850

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4636
Approved symbol	GSTM4
Name	glutathione S-transferase mu 4
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000168765
Ensembl biotype	protein_coding
OMIM	138333
Entrez	2948

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 8 protein_coding_CDS_not_defined

ENST00000326729, ENST00000369833, ENST00000369836, ENST00000461767, ENST00000464733, ENST00000478397, ENST00000479578, ENST00000485640, ENST00000493171, ENST00000493395, ENST00000495742, ENST00000891067, ENST00000891068, ENST00000891069, ENST00000891070, ENST00000939220, ENST00000943027

RefSeq mRNA: 2 — MANE Select: NM_000850 NM_000850, NM_147148

CCDS: CCDS806, CCDS807

Canonical transcript exons

ENST00000369836 — 8 exons

Exon	Start	End
ENSE00001451023	109656099	109656425
ENSE00003522454	109657772	109657872
ENSE00003541580	109659000	109659110
ENSE00003571389	109657215	109657279
ENSE00003618787	109656712	109656787
ENSE00003628080	109657590	109657671
ENSE00003680141	109661165	109661700
ENSE00003686501	109658814	109658909

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 96.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.1556 / max 942.0712, expressed in 1780 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4438	17.2165	1768
4441	7.7099	1467
4440	2.6737	1166
4439	1.1604	604
4437	0.3952	221

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	96.55	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.01	gold quality
mucosa of transverse colon	UBERON:0004991	95.60	gold quality
small intestine	UBERON:0002108	94.87	gold quality
transverse colon	UBERON:0001157	94.72	gold quality
left ovary	UBERON:0002119	94.56	gold quality
apex of heart	UBERON:0002098	94.50	gold quality
right ovary	UBERON:0002118	94.45	gold quality
metanephros cortex	UBERON:0010533	94.29	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.05	gold quality
gastrocnemius	UBERON:0001388	93.85	gold quality
muscle of leg	UBERON:0001383	93.82	gold quality
rectum	UBERON:0001052	93.34	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.10	gold quality
lower esophagus	UBERON:0013473	93.09	gold quality
right lobe of liver	UBERON:0001114	92.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.95	gold quality
right lobe of thyroid gland	UBERON:0001119	92.44	gold quality
duodenum	UBERON:0002114	92.36	gold quality
mucosa of stomach	UBERON:0001199	92.22	gold quality
right adrenal gland	UBERON:0001233	92.08	gold quality
left lobe of thyroid gland	UBERON:0001120	92.00	gold quality
anterior cingulate cortex	UBERON:0009835	91.85	gold quality
left adrenal gland cortex	UBERON:0035825	91.78	gold quality
cingulate cortex	UBERON:0003027	91.72	gold quality
left adrenal gland	UBERON:0001234	91.71	gold quality
right atrium auricular region	UBERON:0006631	91.71	gold quality
stromal cell of endometrium	CL:0002255	91.67	gold quality
right frontal lobe	UBERON:0002810	91.62	gold quality
tibial artery	UBERON:0007610	91.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	22.13
E-GEOD-125970	yes	18.68
E-ANND-3	yes	7.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EWSR1

miRNA regulators (miRDB)

31 targeting GSTM4, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-6824-5P	97.41	68.43	583
HSA-MIR-6835-5P	95.81	64.27	500
HSA-MIR-4772-5P	95.60	68.04	617

Literature-anchored findings (GeneRIF, showing 7)

• A T2517C polymorphism in the GSTM4 gene is associated with risk of developing lung cancer. (PMID:12140136)
• a novel splice variant of GSTM4 that resulted from tandem skipping of exons 4 and 5 is identified. (PMID:16854533)
• GSTM4 (glutathione S-transferase mu 4) haplotype 1101000 may be an important determinant for lung function growth (PMID:19151192)
• GSTM4 contributes to the cancerous behavior of Ewing’s sarcoma. (PMID:19718047)
• We observed suggestive associations between survival and GSTT1 copy number and GSTA5, GSTM4, and ABCC4 single nucleotide polymorphisms (PMID:20200426)
• There were no significant associations between glutathione-S-transferases and p53 expressions and tumor stage, tumor grade and smoking status (p>0.05). (PMID:20529827)
• Our data suggest that the combined treatment with chemotherapy and GST(GSTM1, GSTM4 and GSTT1 ) inhibitors such as EA might be an interesting option for patients with chemoresistant Hodgkin’s lymphoma (PMID:27466493)

Cross-species orthologs

39 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gstm4	ENSMUSG00000027890
rattus_norvegicus	Gstm4	ENSRNOG00000019221
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		WBGENE00001772
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), GSTA4 (ENSG00000170899), GSTA3 (ENSG00000174156), GSTA5 (ENSG00000182793), GSTM2 (ENSG00000213366), GSTA1 (ENSG00000243955), GSTA2 (ENSG00000244067)

Protein

Protein identifiers

Glutathione S-transferase Mu 4 — Q03013 (reviewed: Q03013)

Alternative names: GST class-mu 4, GST-Mu2, GSTM4-4, Leukotriene C4 synthase GSTM4

All UniProt accessions (3): Q03013, A0A140VKE3, A6NNT0

UniProt curated annotations — full annotation on UniProt →

Function. Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes the conjugation of leukotriene A4 with reduced glutathione (GSH) to form leukotriene C4. Can also catalyze the transfer of a glutathionyl group from glutathione (GSH) to 13(S),14(S)-epoxy-docosahexaenoic acid to form maresin conjugate in tissue regeneration 1 (MCTR1), a bioactive lipid mediator that possess potent anti-inflammatory and proresolving actions.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in a wide variety of tissues.

Similarity. Belongs to the GST superfamily. Mu family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q03013-1	1	yes
Q03013-2	2
Q03013-3	3

RefSeq proteins (2): NP_000841, NP_671489 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003081	GST_mu	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: PF00043, PF02798

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), 4 shown:

• RX + glutathione = an S-substituted glutathione + a halide anion + H(+) (RHEA:16437)
• leukotriene C4 = leukotriene A4 + glutathione (RHEA:17617)
• 1-chloro-2,4-dinitrobenzene + glutathione = 2,4-dinitrophenyl-S-glutathione + chloride + H(+) (RHEA:51220)
• (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + glutathione = (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate (RHEA:53508)

UniProt features (36 total): helix 9, sequence variant 6, strand 5, binding site 5, splice variant 3, sequence conflict 3, domain 2, turn 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4GTU	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03013-F1	98.26	1.00

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 (5): 7–8; 46–50; 59–60; 72–73; 116

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-156590	Glutathione conjugation
R-HSA-9026762	Biosynthesis of maresin conjugates in tissue regeneration (MCTR)

MSigDB gene sets: 163 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_FATTY_ACID_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_BENZENE_CONTAINING_COMPOUND_METABOLIC_PROCESS, REACTOME_GLUTATHIONE_CONJUGATION

GO Biological Process (5): glutathione metabolic process (GO:0006749), nitrobenzene metabolic process (GO:0018916), xenobiotic catabolic process (GO:0042178), long-chain fatty acid biosynthetic process (GO:0042759), lipid metabolic process (GO:0006629)

GO Molecular Function (9): glutathione transferase activity (GO:0004364), leukotriene-C4 synthase activity (GO:0004464), enzyme binding (GO:0019899), protein homodimerization activity (GO:0042803), glutathione binding (GO:0043295), protein binding (GO:0005515), transferase activity (GO:0016740), lyase activity (GO:0016829), identical protein binding (GO:0042802)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Biosynthesis of DHA-derived sulfido conjugates	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
catalytic activity	2
cellular anatomical structure	2
modified amino acid metabolic process	1
sulfur compound metabolic process	1
benzene-containing compound metabolic process	1
xenobiotic metabolic process	1
catabolic process	1
long-chain fatty acid metabolic process	1
fatty acid biosynthetic process	1
primary metabolic process	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
carbon-sulfur lyase activity	1
identical protein binding	1
protein dimerization activity	1
anion binding	1
modified amino acid binding	1
oligopeptide binding	1
sulfur compound binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSTM4	GSTZ1	O43708	840
GSTM4	AP5M1	Q9H0R1	759
GSTM4	SLCO6A1	Q86UG4	747
GSTM4	GSTT2B	P0CG30	643
GSTM4	MGST3	O14880	619
GSTM4	GSTA4	O15217	611
GSTM4	GSTK1	Q9Y2Q3	538
GSTM4	GSTO1	P78417	514
GSTM4	GCLC	P48506	505
GSTM4	GSTO2	Q9H4Y5	464
GSTM4	CYP2B6	P20813	457
GSTM4	FLII	Q13045	449
GSTM4	MGST1	P10620	449
GSTM4	PHYH	O14832	446
GSTM4	MGST2	Q99735	446

IntAct

32 interactions, top by confidence:

A	B	Type	Score
GSTM5	GSTM3	psi-mi:“MI:0914”(association)	0.830
GSTM4	GSTM3	psi-mi:“MI:0915”(physical association)	0.740
GSTM3	GSTM4	psi-mi:“MI:0915”(physical association)	0.740
GSTM5	GSTM4	psi-mi:“MI:0915”(physical association)	0.670
GSTM3	GSTM4	psi-mi:“MI:0915”(physical association)	0.560
GSTM4	GSTM3	psi-mi:“MI:0915”(physical association)	0.560
APP	GSTM4	psi-mi:“MI:0915”(physical association)	0.560
GSTM2	GSTM3	psi-mi:“MI:0914”(association)	0.530
GSTM3	ECT2L	psi-mi:“MI:0914”(association)	0.530
GSTM3	GSTM2	psi-mi:“MI:0914”(association)	0.530
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
GSTM3	IKBKB	psi-mi:“MI:0914”(association)	0.350
GSTM5	GSTM1	psi-mi:“MI:0914”(association)	0.350
GSTM2	GSTM1	psi-mi:“MI:0914”(association)	0.350
GSTM5	GSTM4	psi-mi:“MI:0915”(physical association)	0.000
GSTM3	GSTM4	psi-mi:“MI:0915”(physical association)	0.000
GSTM4	RIF1	psi-mi:“MI:0915”(physical association)	0.000
GSTM4	TLE1	psi-mi:“MI:0915”(physical association)	0.000
GSTM4	TP53	psi-mi:“MI:0915”(physical association)	0.000
GSTM4	UNC119	psi-mi:“MI:0915”(physical association)	0.000
GSTM4	APLP1	psi-mi:“MI:0915”(physical association)	0.000
GSTM4	MED31	psi-mi:“MI:0915”(physical association)	0.000
GSTM4	IGSF21	psi-mi:“MI:0915”(physical association)	0.000
GSTM4	ZBTB16	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): GSTM4 (Two-hybrid), GSTM4 (Affinity Capture-MS), GSTM4 (Affinity Capture-MS), GSTM4 (Affinity Capture-MS), GSTM4 (Affinity Capture-MS), GSTM4 (Affinity Capture-MS), GSTM4 (Affinity Capture-MS), GSTM4 (Affinity Capture-MS), GSTM4 (Proximity Label-MS), APLP1 (Two-hybrid), MED31 (Two-hybrid), IGSF21 (Two-hybrid), ZBTB16 (Two-hybrid), GSTM4 (Two-hybrid), LRIF1 (Two-hybrid)

ESM2 similar proteins: A0A1W2PR19, A6QQZ0, O09131, O65857, O76483, O88741, P09488, P0CG29, P0CG30, P21266, P28161, P28342, P30109, P30568, P30713, P42760, P46409, P46430, P46439, P46440, P48774, P57108, P78417, Q01579, Q03013, Q03425, Q03662, Q4V8E6, Q5BK56, Q5R8E8, Q61133, Q64471, Q84TK0, Q8R5I6, Q8TB36, Q9BEA9, Q9BEB0, Q9C6C8, Q9D4P7, Q9FE46

Diamond homologs: M1RIR6, O35543, O35660, P00502, P04905, P08009, P08010, P08515, P09488, P10649, P15626, P15964, P16413, P19639, P20136, P21266, P28161, P30112, P30116, P31670, P31671, P35661, P46409, P46419, P46427, P46436, P46439, P48774, P51781, P56598, P86214, Q00285, Q03013, Q5BK56, Q5R8E8, Q80W21, Q8JFZ2, Q8R5I6, Q9BEA9, Q9BEB0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1322 predictions. Top by Δscore:

Variant	Effect	Δscore
1:109656424:GG:G	donor_gain	1.0000
1:109656425:GG:G	donor_gain	1.0000
1:109656710:AGCT:A	acceptor_gain	1.0000
1:109656711:GCTG:G	acceptor_gain	1.0000
1:109656768:G:GT	donor_gain	1.0000
1:109656826:C:G	donor_gain	1.0000
1:109657280:G:GG	donor_gain	1.0000
1:109657493:G:GG	donor_gain	1.0000
1:109657584:A:AG	acceptor_gain	1.0000
1:109657588:A:AG	acceptor_gain	1.0000
1:109657589:G:GG	acceptor_gain	1.0000
1:109657667:CCTGT:C	donor_gain	1.0000
1:109657668:CTGT:C	donor_gain	1.0000
1:109657669:TGTG:T	donor_loss	1.0000
1:109657670:GT:G	donor_gain	1.0000
1:109657671:TG:T	donor_loss	1.0000
1:109657672:G:GG	donor_gain	1.0000
1:109657673:T:G	donor_loss	1.0000
1:109657674:G:GG	donor_loss	1.0000
1:109657763:G:A	acceptor_gain	1.0000
1:109657767:GGCAG:G	acceptor_loss	1.0000
1:109657768:GCAGG:G	acceptor_loss	1.0000
1:109657769:CAG:C	acceptor_loss	1.0000
1:109657770:AGG:A	acceptor_loss	1.0000
1:109657771:GGT:G	acceptor_gain	1.0000
1:109657868:ACTTT:A	donor_gain	1.0000
1:109657869:CTTT:C	donor_gain	1.0000
1:109657870:TTT:T	donor_gain	1.0000
1:109657871:TT:T	donor_gain	1.0000
1:109657873:G:GG	donor_gain	1.0000

AlphaMissense

1456 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:109657238:T:A	W46R	0.978
1:109657238:T:C	W46R	0.978
1:109656411:T:A	W8R	0.975
1:109656411:T:C	W8R	0.975
1:109656413:G:C	W8C	0.971
1:109656413:G:T	W8C	0.971
1:109659015:T:C	F158L	0.970
1:109659017:C:A	F158L	0.970
1:109659017:C:G	F158L	0.970
1:109656408:T:C	Y7H	0.968
1:109657271:T:C	F57L	0.962
1:109657273:T:A	F57L	0.962
1:109657273:T:G	F57L	0.962
1:109656423:G:A	G12R	0.959
1:109656423:G:C	G12R	0.959
1:109657654:C:A	A81D	0.958
1:109656420:C:A	R11S	0.957
1:109661204:T:C	F203L	0.955
1:109661206:C:A	F203L	0.955
1:109661206:C:G	F203L	0.955
1:109657855:T:C	C115R	0.954
1:109659012:G:C	D157H	0.953
1:109661235:C:A	A213D	0.953
1:109657657:G:C	R82P	0.951
1:109657240:G:C	W46C	0.950
1:109657240:G:T	W46C	0.950
1:109656424:G:A	G12E	0.949
1:109656405:G:T	G6W	0.948
1:109658874:T:C	F141L	0.948
1:109658876:C:A	F141L	0.948

dbSNP variants (sampled 300 via entrez): RS1000176947 (1:109665711 T>C), RS1000192318 (1:109664851 G>A), RS1000412925 (1:109664877 T>A,C), RS1000484939 (1:109665256 T>C), RS1000659236 (1:109658629 A>G), RS1001104773 (1:109655062 A>G), RS1001357816 (1:109654813 C>A), RS1002056775 (1:109656004 C>G), RS1002110414 (1:109656074 G>A), RS1002144305 (1:109666159 C>T), RS1002486044 (1:109668224 G>T), RS1002601165 (1:109662191 A>G), RS1003061271 (1:109656937 G>C), RS1003261617 (1:109662776 T>C), RS1004228636 (1:109660217 A>T)

Disease associations

OMIM: gene MIM:138333 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007102_4	Seasonality and depression	3.000000e-06
GCST011955_7	Alcohol dependence	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006876	seasonality measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2100 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs560018	GSTM4		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, affects cotreatment	6
Air Pollutants	decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
bisphenol A	affects expression, increases expression	2
Dinitrochlorobenzene	affects metabolic processing, affects cotreatment	2
Glutathione	affects metabolic processing, increases metabolic processing, affects cotreatment	2
Gold	increases expression, affects binding, decreases expression	2
Nickel	decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Aflatoxin B1	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
GSK-J4	decreases expression	1
bufotalin	decreases expression	1
apocarotenal	decreases expression	1
lasiocarpine	decreases expression	1
chlortoluron	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects acetylation, affects methylation	1
ochratoxin A	decreases expression	1
periodate-oxidized adenosine	affects expression	1
desethylamodiaquine	affects cotreatment, increases metabolic processing	1
nefazodone	affects cotreatment, decreases expression	1
amodiaquine quinoneimine	affects cotreatment, increases metabolic processing	1
monomethylarsonous acid	affects acetylation, affects methylation	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Bortezomib	decreases expression	1
Atazanavir Sulfate	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743230	ADMET	Substrates for human cytosolic glutathione transferase GSTM4	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1TA	Abcam HeLa GSTM4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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