MT1G

Summary

MT1G (metallothionein 1G, HGNC:7399) is a protein-coding gene on chromosome 16q13, encoding Metallothionein-1G (P13640). Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids. It is a selective cancer dependency (DepMap: 11.3% of cell lines).

Enables zinc ion binding activity. Involved in several processes, including cellular response to cadmium ion; cellular response to copper ion; and cellular response to zinc ion. Located in cytoplasm and nucleus.

Source: NCBI Gene 4495 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 28 total
• Cancer dependency (DepMap): dependent in 11.3% of screened cell lines
• MANE Select transcript: NM_001301267

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7399
Approved symbol	MT1G
Name	metallothionein 1G
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	MT1K
Ensembl gene	ENSG00000125144
Ensembl biotype	protein_coding
OMIM	156353
Entrez	4495

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000379811, ENST00000444837, ENST00000568675, ENST00000569500, ENST00000929125

RefSeq mRNA: 2 — MANE Select: NM_001301267 NM_001301267, NM_005950

CCDS: CCDS10766, CCDS76873

Canonical transcript exons

ENST00000379811 — 3 exons

Exon	Start	End
ENSE00000000031	56666730	56666970
ENSE00001767099	56667312	56667380
ENSE00003902588	56667966	56668065

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 197.6123 / max 32115.9310, expressed in 1009 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157495	197.6123	1009

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.92	gold quality
right lobe of liver	UBERON:0001114	99.88	gold quality
ileal mucosa	UBERON:0000331	99.78	gold quality
adult mammalian kidney	UBERON:0000082	99.67	gold quality
right lobe of thyroid gland	UBERON:0001119	99.63	gold quality
liver	UBERON:0002107	99.62	gold quality
left lobe of thyroid gland	UBERON:0001120	99.59	gold quality
buccal mucosa cell	CL:0002336	99.52	gold quality
thyroid gland	UBERON:0002046	99.51	gold quality
body of pancreas	UBERON:0001150	99.33	gold quality
nephron tubule	UBERON:0001231	99.33	gold quality
rectum	UBERON:0001052	99.28	gold quality
adult organism	UBERON:0007023	99.19	gold quality
kidney epithelium	UBERON:0004819	99.16	gold quality
tongue squamous epithelium	UBERON:0006919	98.93	gold quality
metanephric glomerulus	UBERON:0004736	98.88	gold quality
renal glomerulus	UBERON:0000074	98.78	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.75	gold quality
colonic mucosa	UBERON:0000317	98.61	gold quality
olfactory bulb	UBERON:0002264	98.56	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.53	gold quality
inferior olivary complex	UBERON:0002127	98.18	gold quality
duodenum	UBERON:0002114	98.12	gold quality
medial globus pallidus	UBERON:0002477	98.10	gold quality
cingulate cortex	UBERON:0003027	98.07	gold quality
tibialis anterior	UBERON:0001385	98.06	gold quality
lateral globus pallidus	UBERON:0002476	98.04	gold quality
anterior cingulate cortex	UBERON:0009835	98.04	gold quality
putamen	UBERON:0001874	98.01	gold quality
cartilage tissue	UBERON:0002418	98.00	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 33.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	63370.06
E-MTAB-8221	yes	45609.29
E-MTAB-7407	yes	34489.32
E-CURD-98	yes	24893.91
E-MTAB-9841	yes	22142.83
E-MTAB-10885	yes	21423.53
E-GEOD-130473	yes	19763.29
E-MTAB-9906	yes	16615.41
E-MTAB-10283	yes	13096.60
E-CURD-122	yes	11786.51
E-HCAD-9	yes	11690.24
E-MTAB-10855	yes	10878.99
E-MTAB-8142	yes	6198.20
E-HCAD-38	yes	5115.16
E-MTAB-8410	yes	4307.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F2, E2F3, E2F4, E2F5, SPI1

miRNA regulators (miRDB)

8 targeting MT1G, 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-513A-5P	100.00	69.77	2465
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-6794-3P	98.76	66.99	894

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 27)

• Loss of metallothionein 1G function due to hypermethylation of its promoter leads to athogenesis of papillary thyroid carcinoma (PMID:12640681)
• Induction of the hMT1G promoter by VEGF and heavy metals occurs through the utilization of different transcription factors. (PMID:15735762)
• Eight MT genes were up-regulated after treatment of T-ALL cells with 0.15 and 1.5 microg/mL of metal ores. Heavy metal binding activity. (PMID:15747776)
• MT1G is hypermethylated in renal cell carcinoma. (PMID:18639284)
• Using a panel of four genes (AHRR, p16INK4a, MT1G, and CLDN3) resulted in sensitivity and specificity of 50% and 68%, respectively and may have utility for early detection of esophageal squamous dysplasia and early ESCC. (PMID:19137073)
• Promoter methylation and differential gene expression of five markers: COL1A2, NPM2, HSPB6, DDIT4L and MT1G were validated by sequencing of bisulfite-modified DNA and real-time reverse transcriptase PCR, respectively. (PMID:19491193)
• p16INK4A, DAPK1, PTEN and MT1G genes were not frequently methylated in the stage I non-small cell lung cancer in China. (PMID:19506903)
• MT1G acts as a tumor suppressor gene in hepatocellular carcinoma (PMID:19639168)
• Results describe MT1G promoter hypermethylation in hepatoblastoma and demonstrate that aberrant methylation is a frequent event in this malignancy. (PMID:20032811)
• Increases in MT gene expression and intracellular zinc levels may contribute directly to maintenance of an immune-activated monocyte by mediating an increased resistance to apoptosis during active HIV-1 viremia. (PMID:20551211)
• MT-1A, -1F, -1G, -1X and -2A isoforms are significantly down-regulated in proliferating keloid fibroblasts. (PMID:20812968)
• GPR56, MT1G, and RASSF1 might be the potential methylation markers associated with acquired multidrug resistance of lung adenocarcinoma. (PMID:23902976)
• Metallothionein 1G functions as a tumor suppressor in thyroid cancer through modulating the PI3K/Akt signaling pathway. (PMID:24098937)
• Metallothionein 1G and zinc sensitize human colorectal cancer cells to chemotherapy. (PMID:24634414)
• MT1G was down-regulated in renal cell carcinogenesis. (PMID:24662736)
• MT1M and MT1G promoter methylation may be used as serum biomarkers for noninvasive detection of hepatocellular carcinoma. (PMID:24782625)
• PU.1 suppressive target gene, metallothionein 1G, inhibits retinoic acid-induced NB4 cell differentiation (PMID:25072246)
• These findings indicate that MT1 constitute a biomarker adapted for exploring the impact of sorafenib on the redox metabolism of cancer cells. (PMID:27184800)
• A new tumor-suppressor activity of MT1G in colorectal cancer cells.MT1G role in cell differentiation. (PMID:28393194)
• In clear cell renal cell carcinoma (RCC) MT1E, MT1G and MT1M expression was higher than that noted in other histological tumor subtypes (all P<0.0500). In addition, some associations were observed between metabolic syndromerelated clinical parameters and promoter methylation or gene expression (PMID:31002354)
• Multivariate analysis indicated that RUNX3 and CDH1 promoter methylation were independent prognostic factors for overall survival (P = 0.03 and 0.04; respectively), while DAPK1, RUNX3 and MT1G PM were independent prognostic factors for disease free survival. (PMID:31093876)
• The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. (PMID:32870474)
• Metallothionein-1G suppresses pancreatic cancer cell stemness by limiting activin A secretion via NF-kappaB inhibition. (PMID:33537082)
• Upregulation of Metallothionein-1G Accelerates G1/S Transition in the Growth Phase of Acute Promyelocytic Leukemia NB4 Cells. (PMID:33653779)
• MT1G Regulates c-MYC/P53 Signal to Inhibit Proliferation, Invasion and Migration and Promote Apoptosis in Colon Cancer Cells. (PMID:36999424)
• Bioinformatics analysis and validation of mesenchymal stem cells related gene MT1G in osteosarcoma. (PMID:38747739)
• MT1G induces lipid droplet accumulation through modulation of H3K14 trimethylation accelerating clear cell renal cell carcinoma progression. (PMID:38906969)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	mt2	ENSDARG00000041623

Paralogs (11): MT3 (ENSG00000087250), MT4 (ENSG00000102891), MT2A (ENSG00000125148), MT1B (ENSG00000169688), MT1E (ENSG00000169715), MT1X (ENSG00000187193), MT1F (ENSG00000198417), MT1H (ENSG00000205358), MT1A (ENSG00000205362), MT1M (ENSG00000205364), MT1HL1 (ENSG00000244020)

Protein

Protein identifiers

Metallothionein-1G — P13640 (reviewed: P13640)

Alternative names: Metallothionein-1K, Metallothionein-IG

All UniProt accessions (2): P13640, H3BSF1

UniProt curated annotations — full annotation on UniProt →

Function. Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.

Subunit / interactions. Monomer.

Domain organisation. Class I metallothioneins contain 2 metal-binding domains: four divalent ions are chelated within cluster A of the alpha domain and are coordinated via cysteinyl thiolate bridges to 11 cysteine ligands. Cluster B, the corresponding region within the beta domain, can ligate three divalent ions to 9 cysteines.

Similarity. Belongs to the metallothionein superfamily. Type 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P13640-1	1	yes
P13640-2	2

RefSeq proteins (2): NP_001288196, NP_005941 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000006	Metalthion_vert	Family
IPR017854	Metalthion_dom_sf	Homologous_superfamily
IPR018064	Metalthion_vert_metal_BS	Binding_site
IPR023587	Metalthion_dom_sf_vert	Homologous_superfamily

Pfam: PF00131

UniProt features (34 total): binding site 28, region of interest 2, modified residue 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13640-F1	78.99	0.00

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 (28): 22; 25; 25; 27; 30; 34; 35; 35; 37; 38; 38; 42 …

Post-translational modifications (2): 1, 59

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5661231	Metallothioneins bind metals
R-HSA-5660526	Response to metal ions
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 186 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_ZINC_ION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_CELLULAR_RESPONSE_TO_CADMIUM_ION, GOBP_GROWTH, MODULE_453, GOBP_RESPONSE_TO_COPPER_ION, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP, GOBP_RESPONSE_TO_METAL_ION, MODULE_66, BROWNE_HCMV_INFECTION_48HR_DN, MUELLER_PLURINET, GOBP_MYELOID_LEUKOCYTE_ACTIVATION, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN

GO Biological Process (9): intracellular zinc ion homeostasis (GO:0006882), detoxification of copper ion (GO:0010273), monocyte differentiation (GO:0030224), cellular response to vascular endothelial growth factor stimulus (GO:0035924), monocyte activation (GO:0042117), negative regulation of growth (GO:0045926), cellular response to cadmium ion (GO:0071276), cellular response to copper ion (GO:0071280), cellular response to zinc ion (GO:0071294)

GO Molecular Function (3): zinc ion binding (GO:0008270), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Response to metal ions	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to metal ion	3
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
detoxification of inorganic compound	1
stress response to copper ion	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
cellular response to growth factor stimulus	1
myeloid leukocyte activation	1
growth	1
regulation of growth	1
negative regulation of biological process	1
response to cadmium ion	1
response to copper ion	1
response to zinc ion	1
transition metal ion binding	1
cation binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

667 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MT1G	CISD1	Q9NZ45	507
MT1G	GPX4	P36969	466
MT1G	ACSL4	O60488	446
MT1G	SLC30A1	Q9Y6M5	427
MT1G	NCOA4	Q13772	419
MT1G	EMC2	Q15006	407
MT1G	ATP5MC3	P48201	399
MT1G	MTF1	Q14872	398
MT1G	CARS1	P49589	391
MT1G	FTH1	P02794	389
MT1G	MT1A	P04731	387
MT1G	MT1F	P04733	381
MT1G	LOX	P28300	379
MT1G	SLC7A11	Q9UPY5	373
MT1G	LPCAT3	Q6P1A2	371

IntAct

6 interactions, top by confidence:

A	B	Type	Score
MT1G	SPINK7	psi-mi:“MI:0915”(physical association)	0.550
SPINK7	MT1G	psi-mi:“MI:0915”(physical association)	0.550
MT1M	PGP	psi-mi:“MI:0914”(association)	0.350
MT1G	epd	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): MT1G (Two-hybrid), MT1G (Two-hybrid), MT1G (Affinity Capture-MS), MT1G (Affinity Capture-MS), TP53 (Affinity Capture-Western), MT1G (Affinity Capture-MS), MT1G (Proximity Label-MS), MT1G (Proximity Label-MS), MT1G (Affinity Capture-RNA), MT1G (Two-hybrid)

ESM2 similar proteins: A1L3X4, O18842, O42152, P02797, P02798, P02800, P02801, P02802, P02803, P02804, P04355, P04731, P04733, P07438, P09577, P09578, P0DM35, P11957, P13640, P14425, P15786, P17808, P18055, P25713, P27087, P37360, P55942, P55943, P55944, P58280, P67981, P67982, P67983, P68041, P68301, P68302, P68303, P68304, P79376, P79377

Diamond homologs: O18842, O19000, P02795, P02797, P02798, P02800, P02801, P02802, P02803, P02804, P04355, P04731, P04732, P04733, P07438, P09577, P09578, P0DM35, P11957, P13640, P14425, P17808, P18055, P47944, P47945, P49068, P55942, P55943, P58280, P67981, P67982, P67983, P68041, P68301, P68302, P68303, P68304, P79376, P79377, P79378

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
E2F1	“up-regulates quantity by expression”	MT1G	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	MT1G	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

451 predictions. Top by Δscore:

Variant	Effect	Δscore
16:56667310:A:AC	donor_gain	1.0000
16:56667311:C:CC	donor_gain	1.0000
16:56667311:CT:C	donor_gain	1.0000
16:56667311:CTCTT:C	donor_gain	1.0000
16:56667378:CTG:C	acceptor_gain	1.0000
16:56666967:CAGC:C	acceptor_gain	0.9900
16:56666971:C:CA	acceptor_loss	0.9900
16:56666971:C:CC	acceptor_gain	0.9900
16:56666972:T:A	acceptor_loss	0.9900
16:56667288:T:TA	donor_gain	0.9900
16:56667305:CACT:C	donor_loss	0.9900
16:56667307:CTCA:C	donor_gain	0.9900
16:56667309:CACTC:C	donor_loss	0.9900
16:56667310:ACT:A	donor_gain	0.9900
16:56667311:CTC:C	donor_gain	0.9900
16:56667376:ACCTG:A	acceptor_gain	0.9900
16:56667377:CCTGC:C	acceptor_gain	0.9900
16:56667379:TG:T	acceptor_gain	0.9900
16:56667381:C:CC	acceptor_gain	0.9900
16:56667965:CCAG:C	donor_gain	0.9900
16:56666966:GCAGC:G	acceptor_gain	0.9800
16:56666967:CAGCC:C	acceptor_gain	0.9800
16:56666968:AGC:A	acceptor_gain	0.9800
16:56666969:GC:G	acceptor_gain	0.9800
16:56666970:CC:C	acceptor_gain	0.9800
16:56667306:A:AC	donor_gain	0.9800
16:56667306:ACTC:A	donor_loss	0.9800
16:56667307:C:CC	donor_gain	0.9800
16:56667311:CTCT:C	donor_gain	0.9800
16:56667315:T:TA	donor_gain	0.9800

AlphaMissense

407 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:56666954:G:C	C38W	0.898
16:56666956:A:G	C38R	0.889
16:56666959:A:G	C37R	0.875
16:56666923:A:G	C49R	0.862
16:56666957:G:C	C37W	0.860
16:56666922:C:G	C49S	0.854
16:56666923:A:T	C49S	0.854
16:56666933:A:C	C45W	0.848
16:56666963:G:C	C35W	0.848
16:56667363:A:G	C16R	0.847
16:56666934:C:G	C45S	0.846
16:56666935:A:T	C45S	0.846
16:56666955:C:G	C38S	0.842
16:56666956:A:T	C38S	0.842
16:56666965:A:G	C35R	0.841
16:56666916:C:G	C51S	0.840
16:56666917:A:T	C51S	0.840
16:56666894:G:C	C58W	0.833
16:56667361:G:C	C16W	0.831
16:56666915:G:C	C51W	0.830
16:56666917:A:G	C51R	0.830
16:56667330:A:G	C27R	0.830
16:56666921:G:C	C49W	0.828
16:56666942:A:C	C42W	0.826
16:56667369:A:G	C14R	0.822
16:56666888:G:C	C60W	0.820
16:56666966:G:C	C34W	0.819
16:56667351:A:G	C20R	0.811
16:56666896:A:G	C58R	0.810
16:56666944:A:G	C42R	0.810

dbSNP variants (sampled 300 via entrez): RS1000057034 (16:56666979 G>A,C), RS1000231292 (16:56669234 G>A), RS1000260807 (16:56669429 T>C), RS1001898498 (16:56666669 A>G), RS1004767919 (16:56668896 T>C), RS1005246617 (16:56669162 C>A), RS1006904373 (16:56667036 G>A,T), RS1008615050 (16:56668398 C>T), RS1009000255 (16:56668151 T>A), RS1010256784 (16:56669462 G>C,T), RS1010702399 (16:56669639 C>T), RS1012046332 (16:56669216 T>C), RS1014776285 (16:56668949 A>G), RS1015474649 (16:56669709 C>A,T), RS1017722935 (16:56668409 C>A)

Disease associations

OMIM: gene MIM:156353 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001601_1	Gambling	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004699	gambling behaviour

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium	increases expression, increases abundance, affects cotreatment, decreases reaction	17
Cadmium Chloride	increases abundance, affects cotreatment, decreases reaction, increases expression, decreases expression	11
sodium arsenite	affects cotreatment, decreases reaction, increases expression, increases abundance	10
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Zinc	affects cotreatment, increases expression	7
Arsenic Trioxide	affects binding, decreases reaction, increases expression	6
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression, increases expression	5
Copper	increases expression, affects binding, decreases expression	5
Zinc Sulfate	increases expression, increases reaction	5
Estradiol	decreases expression, increases expression, affects cotreatment	4
Tobacco Smoke Pollution	increases expression, affects expression	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation, increases expression	4
Nickel	increases expression	3
Rotenone	decreases expression, increases expression	3
Silver	increases expression	3
Cyclosporine	decreases expression, increases expression	3
Copper Sulfate	decreases expression, increases expression	3
methylmercuric chloride	increases expression	2
zinc chloride	increases expression	2
cupric chloride	increases expression, increases reaction	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression	2
motexafin gadolinium	increases expression, increases reaction	2
(+)-JQ1 compound	affects cotreatment, affects expression, decreases expression	2
Acetaminophen	increases expression	2
Acetylcysteine	affects cotreatment, decreases reaction, increases expression	2
Air Pollutants	increases abundance, increases expression	2
Amiodarone	increases expression	2
Arsenic	affects cotreatment, increases abundance, increases expression	2
Disulfiram	increases expression, increases reaction, affects binding, decreases expression	2

Clinical trials (associated diseases)

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