MT1E

Summary

MT1E (metallothionein 1E, HGNC:7397) is a protein-coding gene on chromosome 16q13, encoding Metallothionein-1E (P04732). 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: 46.2% of cell lines).

Predicted to enable zinc ion binding activity. Involved in cellular response to cadmium ion and cellular response to zinc ion. Located in cytoplasm and nucleus.

Source: NCBI Gene 4493 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 7 total
• Cancer dependency (DepMap): dependent in 46.2% of screened cell lines
• MANE Select transcript: NM_001363555

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7397
Approved symbol	MT1E
Name	metallothionein 1E
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	MTD
Ensembl gene	ENSG00000169715
Ensembl biotype	protein_coding
OMIM	156351
Entrez	4493

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000306061, ENST00000330439, ENST00000568293

RefSeq mRNA: 2 — MANE Select: NM_001363555 NM_001363555, NM_175617

CCDS: CCDS10764, CCDS86530

Canonical transcript exons

ENST00000330439 — 2 exons

Exon	Start	End
ENSE00001306182	56626466	56627112
ENSE00002604640	56625781	56625879

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 680.7614 / max 15076.2614, expressed in 1569 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154238	680.3022	1569
154239	0.4592	276

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.66	gold quality
ileal mucosa	UBERON:0000331	99.61	gold quality
lateral globus pallidus	UBERON:0002476	99.60	gold quality
pericardium	UBERON:0002407	99.59	gold quality
right lobe of liver	UBERON:0001114	99.51	gold quality
synovial joint	UBERON:0002217	99.46	gold quality
globus pallidus	UBERON:0001875	99.36	gold quality
medial globus pallidus	UBERON:0002477	99.32	gold quality
nephron tubule	UBERON:0001231	99.30	gold quality
left uterine tube	UBERON:0001303	99.27	gold quality
liver	UBERON:0002107	99.27	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.23	gold quality
right lobe of thyroid gland	UBERON:0001119	99.21	gold quality
olfactory bulb	UBERON:0002264	99.20	gold quality
kidney epithelium	UBERON:0004819	99.17	gold quality
skin of hip	UBERON:0001554	99.14	gold quality
colonic mucosa	UBERON:0000317	99.10	gold quality
type B pancreatic cell	CL:0000169	99.08	gold quality
left lobe of thyroid gland	UBERON:0001120	99.07	gold quality
substantia nigra	UBERON:0002038	99.04	gold quality
layer of synovial tissue	UBERON:0007616	99.04	gold quality
thyroid gland	UBERON:0002046	99.03	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.01	gold quality
tongue squamous epithelium	UBERON:0006919	99.00	gold quality
cardia of stomach	UBERON:0001162	98.97	gold quality
metanephric glomerulus	UBERON:0004736	98.97	gold quality
renal glomerulus	UBERON:0000074	98.96	gold quality
midbrain	UBERON:0001891	98.96	gold quality
cartilage tissue	UBERON:0002418	98.93	gold quality
ventral tegmental area	UBERON:0002691	98.90	gold quality

Single-cell (SCXA)

Detected in 33 experiment(s), a significant marker in 30.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	17772.39
E-GEOD-124472	yes	9932.86
E-MTAB-10855	yes	9775.13
E-CURD-98	yes	6311.88
E-MTAB-7407	yes	5849.07
E-GEOD-130148	yes	5429.85
E-ANND-2	yes	4374.80
E-MTAB-9906	yes	4158.89
E-MTAB-6308	yes	3586.36
E-MTAB-10283	yes	3548.00
E-CURD-122	yes	3323.29
E-HCAD-9	yes	2848.02
E-MTAB-7249	yes	2248.67
E-CURD-55	yes	1416.66
E-MTAB-10018	yes	815.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOS, FOXF2

miRNA regulators (miRDB)

6 targeting MT1E, 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-4668-3P	100.00	68.74	2635
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-3192-5P	96.98	65.76	1926

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 46.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• 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 ion transporter activity. (PMID:15747776)
• analysis identified genes known to be associated with cell invasion such as versican, and novel ones, including metallothionein 1E (MT1E) and nicotinamide N-methyltransferase (NNMT) (PMID:18724390)
• High frequency of hypermethylation of MT-1E was found in endometrial carcinomas. (PMID:19420986)
• 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)
• MT1E is a potential tumour suppressor gene, whose loss may promote resistance to apoptosis-inducing therapies. (PMID:20848733)
• Our results reveal that menopause influences the adipose tissue expression of many genes, especially of neurexin 3, metallothionein 1E, and keratyn 7, which are associated with the alteration of several key biological processes. (PMID:21358552)
• MT1E can enhance the migration and invasion of human glioma cells by inducing MMP-9 inactivation via the upregulation of NF-kappaB p50. (PMID:22843066)
• Forced MT1E expression rescues both hypersensitivity of CDKAL1 mutant cells to glycolipotoxicity and pancreatic beta-cell dysfunction in vitro and in vivo. (PMID:28538172)
• Metallothionein Genes are Highly Expressed in Malignant Astrocytomas and Associated with Patient Survival. (PMID:30932010)
• 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)
• Identification of MT1E as a novel tumor suppressor in hepatocellular carcinoma. (PMID:32956919)
• Rare Variant in Metallothionein 1E Increases the Risk of Type 2 Diabetes in a Chinese Population. (PMID:37878528)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	mt2	ENSDARG00000041623

Paralogs (11): MT3 (ENSG00000087250), MT4 (ENSG00000102891), MT1G (ENSG00000125144), MT2A (ENSG00000125148), MT1B (ENSG00000169688), MT1X (ENSG00000187193), MT1F (ENSG00000198417), MT1H (ENSG00000205358), MT1A (ENSG00000205362), MT1M (ENSG00000205364), MT1HL1 (ENSG00000244020)

Protein

Protein identifiers

Metallothionein-1E — P04732 (reviewed: P04732)

Alternative names: Metallothionein-IE

All UniProt accessions (2): P04732, H3BU80

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?
P04732-1	1	yes
P04732-2	2

RefSeq proteins (2): NP_001350484, NP_783316 (=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 (33 total): binding site 28, region of interest 2, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04732-F1	81.07	0.02

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): 21; 24; 24; 26; 29; 33; 34; 34; 36; 37; 37; 41 …

Post-translational modifications (1): 1

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: 303 (showing top): GOBP_RESPONSE_TO_ZINC_ION, GCANCTGNY_MYOD_Q6, GOBP_CELLULAR_RESPONSE_TO_CADMIUM_ION, GOBP_GROWTH, GOBP_RESPONSE_TO_COPPER_ION, IIZUKA_LIVER_CANCER_PROGRESSION_L1_G1_UP, CAGCTG_AP4_Q5, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_RESPONSE_TO_METAL_ION, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, WATANABE_COLON_CANCER_MSI_VS_MSS_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, BROWNE_HCMV_INFECTION_14HR_DN, DELYS_THYROID_CANCER_DN, GOBP_DETOXIFICATION

GO Biological Process (6): intracellular zinc ion homeostasis (GO:0006882), detoxification of copper ion (GO:0010273), 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
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

0 interactions, top by confidence (×1000):

IntAct

8 interactions, top by confidence:

A	B	Type	Score
MT1E	CCDC57	psi-mi:“MI:0915”(physical association)	0.560
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
MT1M	PGP	psi-mi:“MI:0914”(association)	0.350
MT1E	CCDC57	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): MT1E (Affinity Capture-MS), CCDC57 (Two-hybrid), MT1E (Proximity Label-MS), MT1E (Affinity Capture-MS), MT1E (Two-hybrid), MT1E (Affinity Capture-MS), MT1E (Affinity Capture-MS), MT1E (Affinity Capture-RNA)

ESM2 similar proteins: O18842, O19000, P02795, P02797, P02798, P02800, P02801, P02802, P02803, P02804, P04355, P04731, P04732, P04733, P07438, P09577, P09578, P0DM35, P11957, P13640, P14425, P17808, P18055, P49068, P55942, P55943, P58280, P67981, P67982, P67983, P68041, P68301, P68302, P68303, P68304, P79376, P79377, P79378, P79379, P79380

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

331 predictions. Top by Δscore:

Variant	Effect	Δscore
16:56626461:TGTAG:T	acceptor_loss	1.0000
16:56626462:GTAGG:G	acceptor_loss	1.0000
16:56626527:GAAGA:G	donor_gain	1.0000
16:56626529:AGA:A	donor_gain	1.0000
16:56626530:GA:G	donor_gain	1.0000
16:56626530:GAG:G	donor_gain	1.0000
16:56626532:G:GG	donor_gain	1.0000
16:56625597:G:T	donor_gain	0.9900
16:56625598:G:T	donor_gain	0.9900
16:56626464:A:AG	acceptor_gain	0.9900
16:56626464:AG:A	acceptor_gain	0.9900
16:56626464:AGGT:A	acceptor_gain	0.9900
16:56626464:AGGTG:A	acceptor_gain	0.9900
16:56626465:G:GC	acceptor_gain	0.9900
16:56626465:GG:G	acceptor_gain	0.9900
16:56626465:GGT:G	acceptor_gain	0.9900
16:56626465:GGTG:G	acceptor_gain	0.9900
16:56626465:GGTGG:G	acceptor_gain	0.9900
16:56626527:G:GT	donor_gain	0.9900
16:56626528:AAGA:A	donor_gain	0.9900
16:56626531:AG:A	donor_loss	0.9900
16:56626532:GTG:G	donor_loss	0.9900
16:56626535:A:AG	donor_gain	0.9900
16:56626535:AGTG:A	donor_loss	0.9900
16:56626536:G:GG	donor_gain	0.9900
16:56625598:G:GT	donor_gain	0.9800
16:56625876:ACTGG:A	donor_loss	0.9800
16:56625878:TGG:T	donor_loss	0.9800
16:56625879:GGTAA:G	donor_loss	0.9800
16:56625880:GT:G	donor_loss	0.9800

AlphaMissense

818 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:56626480:T:C	C15R	0.806
16:56626513:T:C	C26R	0.803
16:56626474:T:C	C13R	0.789
16:56626492:T:C	C19R	0.778
16:56626482:C:G	C15W	0.756
16:56625866:C:G	C5W	0.742
16:56626480:T:A	C15S	0.738
16:56626481:G:C	C15S	0.738
16:56626492:T:A	C19S	0.729
16:56626493:G:C	C19S	0.729
16:56626507:T:C	C24R	0.729
16:56626494:C:G	C19W	0.727
16:56626515:C:G	C26W	0.722
16:56626498:T:C	C21R	0.719
16:56626513:T:A	C26S	0.712
16:56626514:G:C	C26S	0.712
16:56625864:T:C	C5R	0.711
16:56626476:C:G	C13W	0.691
16:56625872:C:G	C7W	0.688
16:56626509:C:G	C24W	0.680
16:56626522:T:C	C29R	0.679
16:56625855:G:C	D2H	0.673
16:56626507:T:A	C24S	0.672
16:56626508:G:C	C24S	0.672
16:56626500:C:G	C21W	0.658
16:56625870:T:C	C7R	0.648
16:56626531:A:C	S32R	0.648
16:56626498:T:A	C21S	0.644
16:56626499:G:C	C21S	0.644
16:56626474:T:A	C13S	0.639

dbSNP variants (sampled 300 via entrez): RS1000698207 (16:56627539 C>T), RS1001299403 (16:56624385 G>A), RS1001392547 (16:56624689 C>A,G), RS1004747675 (16:56627106 A>T), RS1005200567 (16:56624077 T>G), RS1006965817 (16:56625454 G>A), RS1008591627 (16:56626526 A>G), RS1012010617 (16:56627368 T>C), RS1014300243 (16:56627137 T>C), RS1016995154 (16:56624083 G>A), RS1017509507 (16:56626272 G>A), RS1018269496 (16:56625133 A>G), RS1018506974 (16:56624937 G>A,C), RS1023441611 (16:56627150 G>A,C,T), RS1024178711 (16:56624097 G>A)

Disease associations

OMIM: gene MIM:156351 | 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: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium	increases abundance, increases expression, decreases response to substance	14
sodium arsenite	decreases expression, increases expression, affects cotreatment, affects expression	13
Cadmium Chloride	increases abundance, increases expression, affects expression, decreases expression	11
Arsenic Trioxide	affects expression, decreases expression, increases expression	7
Valproic Acid	affects cotreatment, increases expression	6
Benzo(a)pyrene	affects methylation, affects expression, decreases expression, decreases methylation, decreases reaction (+2 more)	5
Zinc	increases expression	4
methylmercuric chloride	decreases expression, increases expression	3
cadmium sulfate	increases expression	3
Silver	increases expression	3
Zinc Sulfate	increases expression, increases reaction	3
Copper Sulfate	decreases expression, increases expression	3
Particulate Matter	increases abundance, increases expression	3
bisphenol A	decreases expression, affects expression	2
lead acetate	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression	2
motexafin gadolinium	increases expression, affects cotreatment	2
Air Pollutants	increases abundance, increases expression	2
Cannabidiol	increases expression, affects cotreatment	2
Copper	affects binding, increases expression	2
Dexamethasone	increases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Estradiol	affects expression, decreases expression, affects cotreatment	2
Lipopolysaccharides	affects expression, affects reaction, affects response to substance, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Rotenone	increases expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Aflatoxin B1	increases expression	2

Clinical trials (associated diseases)

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