MT1X

Summary

MT1X (metallothionein 1X, HGNC:7405) is a protein-coding gene on chromosome 16q13, encoding Metallothionein-1X (P80297). Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.

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

Source: NCBI Gene 4501 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_005952

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7405
Approved symbol	MT1X
Name	metallothionein 1X
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	MT-1l
Ensembl gene	ENSG00000187193
Ensembl biotype	protein_coding
OMIM	156359
Entrez	4501

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000394485, ENST00000562939, ENST00000564974, ENST00000568370, ENST00000894237

RefSeq mRNA: 1 — MANE Select: NM_005952 NM_005952

CCDS: CCDS10768

Canonical transcript exons

ENST00000394485 — 3 exons

Exon	Start	End
ENSE00001636692	56683165	56683230
ENSE00003523937	56682470	56682568
ENSE00003650575	56683958	56684196

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 346.0183 / max 14539.9057, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154264	345.9010	1815
154263	0.1173	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	99.87	gold quality
right lobe of liver	UBERON:0001114	99.83	gold quality
gastrocnemius	UBERON:0001388	99.82	gold quality
right lobe of thyroid gland	UBERON:0001119	99.81	gold quality
left lobe of thyroid gland	UBERON:0001120	99.80	gold quality
skin of abdomen	UBERON:0001416	99.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.76	gold quality
thyroid gland	UBERON:0002046	99.75	gold quality
muscle of leg	UBERON:0001383	99.74	gold quality
skin of leg	UBERON:0001511	99.74	gold quality
tibialis anterior	UBERON:0001385	99.72	gold quality
lateral globus pallidus	UBERON:0002476	99.71	gold quality
ileal mucosa	UBERON:0000331	99.70	gold quality
mucosa of stomach	UBERON:0001199	99.70	gold quality
cartilage tissue	UBERON:0002418	99.67	gold quality
calcaneal tendon	UBERON:0003701	99.66	gold quality
synovial joint	UBERON:0002217	99.65	gold quality
mucosa of transverse colon	UBERON:0004991	99.65	gold quality
lower esophagus mucosa	UBERON:0035834	99.65	gold quality
body of pancreas	UBERON:0001150	99.63	gold quality
inferior olivary complex	UBERON:0002127	99.63	gold quality
left uterine tube	UBERON:0001303	99.62	gold quality
nipple	UBERON:0002030	99.61	gold quality
zone of skin	UBERON:0000014	99.59	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.56	gold quality
type B pancreatic cell	CL:0000169	99.55	gold quality
left coronary artery	UBERON:0001626	99.55	gold quality
popliteal artery	UBERON:0002250	99.55	gold quality
tibial artery	UBERON:0007610	99.55	gold quality
layer of synovial tissue	UBERON:0007616	99.55	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 27.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	21714.35
E-MTAB-10855	yes	12777.85
E-MTAB-9435	yes	9483.30
E-MTAB-8142	yes	8535.43
E-HCAD-9	yes	8358.13
E-MTAB-10553	yes	8263.61
E-CURD-126	yes	8169.93
E-CURD-7	yes	6628.21
E-ENAD-21	yes	6396.26
E-CURD-55	yes	4157.04
E-MTAB-6308	yes	4077.71
E-CURD-98	yes	3618.91
E-MTAB-10283	yes	3419.98
E-HCAD-1	yes	2729.62
E-MTAB-8060	yes	1130.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

10 targeting MT1X, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-6823-5P	96.26	65.69	919

Literature-anchored findings (GeneRIF, showing 12)

• It plays a role in the detoxification of heavy metals and reactive oxygen species. (review) (PMID:19881214)
• 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)
• Our results suggest that MT1XT20 represents a sensitive and specific marker for MSI testing and could be included in a complete set of MSI markers for the confident identification of familial or sporadic dMMR patients in colorectal cancers. (PMID:22108904)
• Results show variation in MTX1 is implicated in disordered gambling (PMID:22780124)
• siRNA-mediated knockdown of TCRP1 and MT1X was found to sensitize cells to cisplatin, leading to increased apoptosis and inhibition of cell proliferation (PMID:23251525)
• These findings suggest that functional interactions between FHL3 and MT-1X may provide some clues to the mechanisms of FHL3-regulated cell proliferation. (PMID:24690879)
• Data show that in the MCF-7 breast cancer cell line, only MT1X metallothioneins (MTs) positively correlated with vascular endothelial growth factor C (VEGFC). (PMID:27107086)
• MT1XT20 Single Quasi-Monomorphic Mononucleotide Marker showing Microsatellite Instability is associated with Persian Lynch Syndrome (PMID:27797228)
• we featured the expression patterns of MT1s in tissue obtained from various points along the spectrum of hepatocarcinogenesis. Most MT1 members were down-regulated, and MT1X were associated with HCC prognosis. Additionally, MT1X was shown to play a suppressive role in HCC metastasis. (PMID:29873415)
• Metallothionein Genes are Highly Expressed in Malignant Astrocytomas and Associated with Patient Survival. (PMID:30932010)
• MT1X is an oncogene and indicates prognosis in ccRCC. (PMID:36149322)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mt2	ENSDARG00000041623
mus_musculus	Mt2	ENSMUSG00000031762
rattus_norvegicus	Mt2A	ENSRNOG00000043098
rattus_norvegicus		ENSRNOG00000071250

Paralogs (11): MT3 (ENSG00000087250), MT4 (ENSG00000102891), MT1G (ENSG00000125144), MT2A (ENSG00000125148), MT1B (ENSG00000169688), MT1E (ENSG00000169715), MT1F (ENSG00000198417), MT1H (ENSG00000205358), MT1A (ENSG00000205362), MT1M (ENSG00000205364), MT1HL1 (ENSG00000244020)

Protein

Protein identifiers

Metallothionein-1X — P80297 (reviewed: P80297)

Alternative names: Metallothionein-IX

All UniProt accessions (3): A0A140VJP8, P80297, U3KQD7

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. May be involved in FAM168A anti-apoptotic signaling.

Subunit / interactions. Monomer. Interacts with FAM168A.

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_005943* (*=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, modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P80297-F1	79.83	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 …

Post-translational modifications (2): 1, 58

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: 300 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RESPONSE_TO_ZINC_ION, GRUETZMANN_PANCREATIC_CANCER_DN, MCLACHLAN_DENTAL_CARIES_UP, GOBP_RESPONSE_TO_PEPTIDE, CHUANG_OXIDATIVE_STRESS_RESPONSE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_CELLULAR_RESPONSE_TO_CADMIUM_ION, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GOBP_GROWTH, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, KYNG_DNA_DAMAGE_DN

GO Biological Process (8): intracellular zinc ion homeostasis (GO:0006882), response to metal ion (GO:0010038), detoxification of copper ion (GO:0010273), cellular response to erythropoietin (GO:0036018), 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
response to chemical	1
detoxification of inorganic compound	1
stress response to copper ion	1
response to erythropoietin	1
cellular response to cytokine stimulus	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

644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MT1X	NQO1	P15559	685
MT1X	SLC30A1	Q9Y6M5	610
MT1X	APRT	P07741	563
MT1X	FAM168A	Q92567	544
MT1X	GSR	P00390	526
MT1X	PLA2G2A	P14555	520
MT1X	AKT1	P31749	488
MT1X	MTF1	Q14872	454
MT1X	OLFM1	Q99784	431
MT1X	PTPN1	P18031	426
MT1X	ATP7B	P35670	422
MT1X	HMOX1	P09601	420
MT1X	ZWINT	O95229	410
MT1X	MT2A	P02795	404
MT1X	SLC30A2	Q9BRI3	382

IntAct

8 interactions, top by confidence:

A	B	Type	Score
MT1X	SIX6OS1	psi-mi:“MI:0915”(physical association)	0.560
MT1X	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
TERF1	MT1X	psi-mi:“MI:0915”(physical association)	0.370
MT1X	POT1	psi-mi:“MI:0915”(physical association)	0.370
MT1X	TERF2IP	psi-mi:“MI:0915”(physical association)	0.000
MT1X	SIX6OS1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): MT1X (Affinity Capture-MS), MT1X (Two-hybrid), MT1X (Affinity Capture-MS), MT1X (Affinity Capture-MS), MT1X (Co-fractionation), MT1X (Co-fractionation), MT1X (Co-fractionation), MT1X (Co-fractionation), MT1X (Co-fractionation), MT1X (Co-fractionation), MT1X (Co-fractionation), CRYZ (Co-fractionation), SELENBP1 (Co-fractionation), TST (Co-fractionation), MT1X (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

500 predictions. Top by Δscore:

Variant	Effect	Δscore
16:56682564:GCCTG:G	donor_gain	1.0000
16:56682565:CCTGG:C	donor_loss	1.0000
16:56682566:CTGGT:C	donor_loss	1.0000
16:56682569:G:GA	donor_loss	1.0000
16:56682569:G:GG	donor_gain	1.0000
16:56682570:T:A	donor_loss	1.0000
16:56683163:A:AG	acceptor_gain	1.0000
16:56683163:AGTT:A	acceptor_gain	1.0000
16:56683163:AGTTG:A	acceptor_gain	1.0000
16:56683164:G:GA	acceptor_gain	1.0000
16:56683164:GT:G	acceptor_gain	1.0000
16:56683164:GTT:G	acceptor_gain	1.0000
16:56683164:GTTG:G	acceptor_gain	1.0000
16:56683164:GTTGG:G	acceptor_gain	1.0000
16:56683226:GAAGA:G	donor_gain	1.0000
16:56683227:AAGAG:A	donor_loss	1.0000
16:56683228:AGA:A	donor_gain	1.0000
16:56683228:AGAG:A	donor_loss	1.0000
16:56683229:GA:G	donor_gain	1.0000
16:56683229:GAG:G	donor_gain	1.0000
16:56683230:AGTG:A	donor_loss	1.0000
16:56683231:G:GG	donor_gain	1.0000
16:56684072:GAT:G	donor_gain	1.0000
16:56683160:TGCA:T	acceptor_loss	0.9900
16:56683161:GCA:G	acceptor_loss	0.9900
16:56683162:CAGTT:C	acceptor_loss	0.9900
16:56683164:G:A	acceptor_loss	0.9900
16:56683227:AAGA:A	donor_gain	0.9900
16:56683515:G:A	acceptor_gain	0.9900
16:56683160:T:TA	acceptor_gain	0.9800

AlphaMissense

398 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:56683974:C:G	C37W	0.808
16:56683972:T:C	C37R	0.783
16:56683971:C:G	C36W	0.774
16:56683969:T:C	C36R	0.759
16:56683972:T:A	C37S	0.750
16:56683973:G:C	C37S	0.750
16:56683965:C:G	C34W	0.747
16:56683986:T:G	C41W	0.735
16:56683995:T:G	C44W	0.725
16:56683993:T:A	C44S	0.723
16:56683994:G:C	C44S	0.723
16:56683963:T:C	C34R	0.716
16:56682555:C:G	C5W	0.714
16:56684013:C:G	C50W	0.714
16:56684034:C:G	C57W	0.714
16:56684005:T:A	C48S	0.709
16:56684005:T:C	C48R	0.709
16:56684006:G:C	C48S	0.709
16:56683179:T:C	C15R	0.708
16:56683962:C:G	C33W	0.708
16:56684007:C:G	C48W	0.707
16:56684011:T:A	C50S	0.703
16:56684012:G:C	C50S	0.703
16:56683984:T:C	C41R	0.701
16:56683181:T:G	C15W	0.695
16:56684040:C:G	C59W	0.692
16:56683212:T:C	C26R	0.688
16:56683993:T:C	C44R	0.681
16:56682561:C:G	C7W	0.678
16:56684032:T:C	C57R	0.675

dbSNP variants (sampled 300 via entrez): RS1001996969 (16:56681022 T>A,C), RS1002671080 (16:56683370 A>G), RS1003676316 (16:56682425 G>A), RS1006277601 (16:56680701 T>A), RS1006773366 (16:56682836 A>G), RS1008450352 (16:56684059 A>G,T), RS1009379697 (16:56681743 C>T), RS1011028585 (16:56682442 T>C), RS1011618149 (16:56681068 G>A), RS1012063622 (16:56681459 T>C), RS1012272632 (16:56683445 A>G), RS1013457891 (16:56680778 T>C), RS1013652182 (16:56682091 A>C,G), RS1013907488 (16:56680996 G>A,T), RS1015311622 (16:56684484 T>C)

Disease associations

OMIM: gene MIM:156359 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001601_1	Gambling	3.000000e-06
GCST006225_5	Anti-chlamydia trachomatis IgG seropositivity	9.000000e-07
GCST010241_115	Apolipoprotein A1 levels	8.000000e-36

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004699	gambling behaviour
EFO:0009330	Chlamydia trachomatis seropositivity
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases reaction, increases expression, increases abundance, affects cotreatment	17
Cadmium	increases abundance, decreases reaction, increases expression	17
Cadmium Chloride	affects expression, increases abundance, affects cotreatment, decreases reaction, increases expression	13
Arsenic Trioxide	affects binding, decreases reaction, decreases expression, increases expression	9
Zinc	decreases expression, decreases reaction, affects cotreatment, increases expression	9
Estradiol	increases expression, affects cotreatment, decreases expression	8
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Copper	decreases expression, affects binding, decreases reaction, increases expression	7
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	6
Cisplatin	decreases response to substance, decreases reaction, decreases expression, increases response to substance, affects cotreatment (+1 more)	6
Tobacco Smoke Pollution	decreases expression	6
Particulate Matter	increases expression, affects cotreatment, decreases expression, increases abundance	6
Silver	increases expression	5
cupric chloride	decreases expression, increases expression, increases reaction	4
Aflatoxin B1	affects expression, decreases expression, increases expression	4
Zinc Sulfate	increases expression, increases reaction	4
zinc chloride	decreases reaction, increases expression	3
Acetylcysteine	decreases reaction, increases expression, affects cotreatment	3
Air Pollutants	decreases expression, increases abundance, increases expression	3
Disulfiram	increases expression, increases reaction, affects binding, decreases expression	3
Oxygen	decreases expression, increases expression	3
Progesterone	affects cotreatment, increases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
lead acetate	increases expression, affects cotreatment	2
cobaltous chloride	increases expression	2
nickel chloride	increases expression	2
cupric oxide	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases reaction, increases expression, decreases expression	2

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1XQ	Abcam HeLa MT1X KO	Cancer cell line	Female

Clinical trials (associated diseases)

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