MT1M

Summary

MT1M (metallothionein 1M, HGNC:14296) is a protein-coding gene on chromosome 16q13, encoding Metallothionein-1M (Q8N339). Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.

This gene encodes a member of the metallothionein superfamily, type 1 family. Metallothioneins have a high content of cysteine residues that bind various heavy metals. These genes are transcriptionally regulated by both heavy metals and glucocorticoids.

Source: NCBI Gene 4499 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_176870

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14296
Approved symbol	MT1M
Name	metallothionein 1M
Location	16q13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205364
Ensembl biotype	protein_coding
OMIM	156357
Entrez	4499

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000379818, ENST00000570233, ENST00000858452

RefSeq mRNA: 1 — MANE Select: NM_176870 NM_176870

CCDS: CCDS42166

Canonical transcript exons

ENST00000379818 — 3 exons

Exon	Start	End
ENSE00001680657	56633340	56633405
ENSE00002593635	56632659	56632759
ENSE00002606059	56633751	56633981

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 99.35.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0250 / max 4.8449, expressed in 6 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154245	33.0270	799
154243	1.3278	494
154242	0.8397	341
154244	0.7859	361
154241	0.3307	192
154240	0.2086	68
154236	0.0250	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.35	gold quality
left uterine tube	UBERON:0001303	99.27	gold quality
pericardium	UBERON:0002407	99.15	gold quality
right lobe of liver	UBERON:0001114	98.61	gold quality
omental fat pad	UBERON:0010414	98.60	gold quality
peritoneum	UBERON:0002358	98.56	gold quality
lateral globus pallidus	UBERON:0002476	98.40	gold quality
mucosa of stomach	UBERON:0001199	98.31	gold quality
synovial joint	UBERON:0002217	98.13	gold quality
left coronary artery	UBERON:0001626	98.00	gold quality
amygdala	UBERON:0001876	97.92	gold quality
coronary artery	UBERON:0001621	97.76	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.70	gold quality
popliteal artery	UBERON:0002250	97.64	gold quality
tibial artery	UBERON:0007610	97.64	gold quality
substantia nigra	UBERON:0002038	97.53	gold quality
tibial nerve	UBERON:0001323	97.41	gold quality
globus pallidus	UBERON:0001875	97.40	gold quality
rectum	UBERON:0001052	97.37	gold quality
right lobe of thyroid gland	UBERON:0001119	97.30	gold quality
medial globus pallidus	UBERON:0002477	97.25	gold quality
body of stomach	UBERON:0001161	97.19	gold quality
anterior cingulate cortex	UBERON:0009835	97.17	gold quality
aorta	UBERON:0000947	97.16	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.15	gold quality
nucleus accumbens	UBERON:0001882	97.14	gold quality
putamen	UBERON:0001874	97.12	gold quality
cingulate cortex	UBERON:0003027	97.10	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.07	gold quality
upper lobe of left lung	UBERON:0008952	96.92	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-6308	yes	4350.54
E-CURD-126	yes	3071.42
E-ANND-2	yes	2269.91
E-MTAB-8559	yes	1138.82
E-MTAB-8530	yes	758.78
E-CURD-98	yes	714.73
E-MTAB-10018	yes	226.13
E-GEOD-137537	yes	31.96
E-MTAB-7316	yes	26.41
E-MTAB-8410	yes	21.72
E-HCAD-1	yes	18.94
E-GEOD-125970	yes	6.79
E-HCAD-25	yes	5.79
E-MTAB-6058	no	23.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting MT1M, 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-302C-5P	99.97	72.56	3642
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-668-3P	96.18	65.80	673

Literature-anchored findings (GeneRIF, showing 10)

• Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas. (PMID:22971577)
• MT1M and MT1G promoter methylation may be used as serum biomarkers for noninvasive detection of hepatocellular carcinoma. (PMID:24782625)
• miR-24-3p plays an important role in the initiation and progression of hepatocellular carcinoma by targeting metallothionein 1M. (PMID:27650047)
• Low MT1M expression is associated with poor hepatocellular carcinoma prognosis following curative resection. (PMID:27808371)
• Results found that MT1M is downregulated in hepatocellular carcinoma (HCC) tumors, and it suppressed HCC tumorigenesis possibly by inducing cell cycle arrest, enhancing apoptosis and inhibiting cell migration and invasion. These findings provide evidence that MT1M might be a tumor suppressor in HCC tumorigenesis. (PMID:28380433)
• MT1M can suppress hepatocellular carcinoma cell proliferation and induce apoptosis through downregulating Bcl-2, upregulating Bax, and enhancing Caspase-3 activity. (PMID:29461597)
• MiR-545-3p, which served as a tumor promoter, post-transcriptionally regulate MT1M in HCC through binding to its untranslated region (3’UTR). (PMID:30227328)
• 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)
• Metallothionein MT1M Suppresses Carcinogenesis of Esophageal Carcinoma Cells through Inhibition of the Epithelial-Mesenchymal Transition and the SOD1/PI3K Axis. (PMID:33820882)
• MT1M regulates gastric cancer progression and stemness by modulating the Hedgehog pathway protein GLI1. (PMID:37276792)

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), MT1E (ENSG00000169715), MT1X (ENSG00000187193), MT1F (ENSG00000198417), MT1H (ENSG00000205358), MT1A (ENSG00000205362), MT1HL1 (ENSG00000244020)

Protein

Protein identifiers

Metallothionein-1M — Q8N339 (reviewed: Q8N339)

Alternative names: Metallothionein-IM

All UniProt accessions (2): Q8N339, H3BUC6

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.

RefSeq proteins (1): NP_789846* (*=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 (32 total): binding site 28, region of interest 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N339-F1	77.90	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): 21; 24; 24; 26; 29; 33; 34; 34; 36; 37; 37; 41 …

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: 115 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_ZINC_ION, JAEGER_METASTASIS_DN, GOBP_CELLULAR_RESPONSE_TO_CADMIUM_ION, GOBP_GROWTH, GOBP_RESPONSE_TO_COPPER_ION, GOBP_RESPONSE_TO_METAL_ION, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, CAIRO_HEPATOBLASTOMA_DN, GOBP_DETOXIFICATION, GOBP_CELLULAR_RESPONSE_TO_ZINC_ION, GOBP_MONOATOMIC_ION_HOMEOSTASIS, SABATES_COLORECTAL_ADENOMA_DN

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

412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MT1M	OR8D4	Q8NGM9	391
MT1M	MT1A	P04731	376
MT1M	MT1F	P04733	374
MT1M	SLC30A1	Q9Y6M5	371
MT1M	MTF1	Q14872	364
MT1M	ZNF697	Q5TEC3	353
MT1M	CPOX	P36551	327
MT1M	ZNF33A	P17013	315
MT1M	E7EVR1	E7EVR1	311
MT1M	MT1B	P07438	308
MT1M	MAP1S	Q66K74	298
MT1M	ZNF500	O60304	290
MT1M	ZNF710	Q8N1W2	286
MT1M	GLRX	P35754	284
MT1M	Q6IQ01	Q6IQ01	271

IntAct

21 interactions, top by confidence:

A	B	Type	Score
KRTAP5-1	MT1M	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	MT1M	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	MT1M	psi-mi:“MI:0915”(physical association)	0.560
MT1M	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
SMCP	MT1M	psi-mi:“MI:0915”(physical association)	0.560
MT1M	KRTAP17-1	psi-mi:“MI:0915”(physical association)	0.560
RELB	MT1M	psi-mi:“MI:0915”(physical association)	0.370
MT1M	PGP	psi-mi:“MI:0914”(association)	0.350
MT1M	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000
MT1M	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
MT1M	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.000
MT1M	DDIT4L	psi-mi:“MI:0915”(physical association)	0.000
MT1M	SMCP	psi-mi:“MI:0915”(physical association)	0.000
MT1M	KRTAP17-1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): MT1M (Two-hybrid), MT1M (Two-hybrid), MT1M (Two-hybrid), MT1M (Two-hybrid), KRTAP5-1 (Two-hybrid), KRTAP5-9 (Two-hybrid), MT1M (Two-hybrid), MT1M (Reconstituted Complex), MT1M (Biochemical Activity), NEFH (Affinity Capture-MS), UBA52 (Affinity Capture-MS), TPPP2 (Affinity Capture-MS), PGP (Affinity Capture-MS), MT1E (Affinity Capture-MS), MT1G (Affinity Capture-MS)

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

153 predictions. Top by Δscore:

Variant	Effect	Δscore
16:56633335:TGCA:T	acceptor_loss	1.0000
16:56633336:GCAG:G	acceptor_loss	1.0000
16:56633337:CAG:C	acceptor_loss	1.0000
16:56633338:A:AG	acceptor_gain	1.0000
16:56633338:A:T	acceptor_loss	1.0000
16:56633338:AG:A	acceptor_gain	1.0000
16:56633339:G:GC	acceptor_gain	1.0000
16:56633339:GG:G	acceptor_gain	1.0000
16:56633339:GGT:G	acceptor_gain	1.0000
16:56633401:GAAGA:G	donor_gain	1.0000
16:56633402:AAGA:A	donor_gain	1.0000
16:56633403:AGA:A	donor_gain	1.0000
16:56633403:AGAG:A	donor_loss	1.0000
16:56633404:GA:G	donor_gain	1.0000
16:56633404:GAG:G	donor_gain	1.0000
16:56633404:GAGTG:G	donor_loss	1.0000
16:56633405:AG:A	donor_loss	1.0000
16:56633406:G:GG	donor_gain	1.0000
16:56633408:GAGT:G	donor_loss	1.0000
16:56633410:G:GG	donor_gain	1.0000
16:56632759:GGTAA:G	donor_loss	0.9900
16:56632760:G:GG	donor_gain	0.9900
16:56632760:G:T	donor_loss	0.9900
16:56632761:T:A	donor_loss	0.9900
16:56633335:T:TA	acceptor_gain	0.9900
16:56633338:AGGT:A	acceptor_gain	0.9900
16:56633339:GGTG:G	acceptor_gain	0.9900
16:56633339:GGTGT:G	acceptor_gain	0.9900
16:56633401:G:GT	donor_gain	0.9900
16:56633407:T:A	donor_loss	0.9900

AlphaMissense

400 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1002637043 (16:56631668 G>A), RS1002996632 (16:56631402 C>A,G), RS1007089339 (16:56630797 A>C,G), RS1007552775 (16:56631163 G>A), RS1012856472 (16:56631474 A>G), RS1018401840 (16:56631169 T>G), RS1021294541 (16:56631736 T>C), RS1025325648 (16:56631187 C>G), RS1031512569 (16:56631795 G>A,C), RS1035368135 (16:56631415 A>G), RS1035760953 (16:56631201 C>G), RS1039662343 (16:56631605 A>G), RS1039906111 (16:56631349 C>T), RS1045618190 (16:56630694 C>A,T), RS1051144063 (16:56631300 G>A)

Disease associations

OMIM: gene MIM:156357 | 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

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

Chemical	Actions (top 5)	PubMed papers
Cadmium	increases abundance, increases expression	10
Cadmium Chloride	increases abundance, increases expression	6
sodium arsenite	affects cotreatment, increases abundance, increases expression	5
Zinc	affects reaction, increases abundance, increases expression, affects cotreatment	5
Valproic Acid	increases methylation, decreases expression, increases expression	4
Particulate Matter	increases abundance, increases expression, decreases expression, affects cotreatment	4
Air Pollutants	increases expression, decreases expression, increases abundance	3
Arsenic	affects cotreatment, affects methylation, increases abundance, increases expression	3
Estradiol	increases expression, affects cotreatment	3
Progesterone	increases expression, affects cotreatment	3
Decitabine	increases expression	2
Copper	affects binding, increases expression	2
Mercury	affects response to substance, affects cotreatment, affects abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silver	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	increases expression	2
Copper Sulfate	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
ML385	decreases reaction, increases expression	1
alexidine	increases expression, affects reaction	1
bisphenol A	affects expression	1
lead acetate	increases expression	1
sodium arsenate	increases abundance, increases expression	1
thallium sulfate	affects reaction, increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
zinc chloride	increases expression	1
isoconazole	increases expression, decreases reaction	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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