MT1F

Summary

MT1F (metallothionein 1F, HGNC:7398) is a protein-coding gene on chromosome 16q13, encoding Metallothionein-1F (P04733). 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 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 4494 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_005949

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7398
Approved symbol	MT1F
Name	metallothionein 1F
Location	16q13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198417
Ensembl biotype	protein_coding
OMIM	156352
Entrez	4494

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000334350, ENST00000564295, ENST00000567672, ENST00000568475, ENST00000858841, ENST00000915665

RefSeq mRNA: 2 — MANE Select: NM_005949 NM_001301272, NM_005949

CCDS: CCDS32456, CCDS76872

Canonical transcript exons

ENST00000334350 — 3 exons

Exon	Start	End
ENSE00001745938	56658675	56658740
ENSE00002576619	56657959	56658086
ENSE00002609936	56659073	56659303

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.8876 / max 3873.8548, expressed in 1429 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154253	26.2163	997
154252	8.4564	1099
154254	6.0022	746
154251	5.8811	1139
154250	0.9878	424
154255	0.3437	123

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nephron tubule	UBERON:0001231	99.55	gold quality
right lobe of thyroid gland	UBERON:0001119	99.45	gold quality
left lobe of thyroid gland	UBERON:0001120	99.43	gold quality
kidney epithelium	UBERON:0004819	99.43	gold quality
mucosa of transverse colon	UBERON:0004991	99.35	gold quality
thyroid gland	UBERON:0002046	99.31	gold quality
renal glomerulus	UBERON:0000074	99.21	gold quality
metanephric glomerulus	UBERON:0004736	99.21	gold quality
adult mammalian kidney	UBERON:0000082	99.16	gold quality
right lobe of liver	UBERON:0001114	99.13	gold quality
ileal mucosa	UBERON:0000331	99.08	gold quality
medial globus pallidus	UBERON:0002477	99.03	gold quality
globus pallidus	UBERON:0001875	98.88	gold quality
lateral globus pallidus	UBERON:0002476	98.72	gold quality
type B pancreatic cell	CL:0000169	98.59	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.48	gold quality
substantia nigra	UBERON:0002038	98.44	gold quality
cartilage tissue	UBERON:0002418	98.39	gold quality
amniotic fluid	UBERON:0000173	98.32	gold quality
midbrain	UBERON:0001891	98.27	gold quality
liver	UBERON:0002107	98.24	gold quality
pericardium	UBERON:0002407	98.20	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.14	gold quality
cranial nerve II	UBERON:0000941	98.11	gold quality
body of pancreas	UBERON:0001150	98.05	gold quality
ventral tegmental area	UBERON:0002691	97.94	gold quality
olfactory bulb	UBERON:0002264	97.85	gold quality
putamen	UBERON:0001874	97.82	gold quality
hypothalamus	UBERON:0001898	97.82	gold quality
adult organism	UBERON:0007023	97.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	4746.23
E-MTAB-9906	yes	2070.00
E-HCAD-38	yes	1993.83
E-CURD-98	yes	1921.04
E-MTAB-7316	yes	1603.41
E-MTAB-10855	yes	545.51
E-MTAB-10018	yes	296.21
E-MTAB-6701	yes	80.17
E-HCAD-10	yes	40.03
E-GEOD-137537	yes	36.66
E-MTAB-10553	yes	31.10
E-GEOD-125970	yes	16.06
E-MTAB-9388	yes	11.85
E-MTAB-7303	no	778.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT1, FOXF2, MYC, NR3C1

miRNA regulators (miRDB)

15 targeting MT1F, 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-4668-3P	100.00	68.74	2635
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-3192-5P	96.98	65.76	1926

Literature-anchored findings (GeneRIF, showing 11)

• In the liver cancer tissue, MT1F shows down-regulated expression that supports the inhibited function of MT1F in cancer growth (PMID:15369632)
• Knockdown of MT1F gene increased particular matter(2.5)-induced H2O2 release in alveolar macrophages. (PMID:19251948)
• MT-1A, -1F, -1G, -1X and -2A isoforms are significantly down-regulated in proliferating keloid fibroblasts. (PMID:20812968)
• MT-1 rs8052394 A allele is associated with oral squamous cell carcinoma. (PMID:21128001)
• Studies provide the mechanistic properties of metal binding for metallothionein metallation. (PMID:21409206)
• This study identifies for the first time the relevant metallothionein isoforms for colorectal cancer progression. (PMID:21820154)
• MT1F is a putative tumor suppressor gene in colon carcinogenesis that is downregulated mainly by loss of heterozygosity in colon cancer tissue (PMID:22426038)
• findings show 5 MT isoforms were overexpressed in non-small cell lung cancer and overexpression of MT-1F and MT-2A predicted poor outcome; both isoforms may be involved in progression of this cancer type; upregulated MT-1F expression associated with larger primary tumor size and higher grade of malignanacy (PMID:23064051)
• Metallothionein may have a role in the control of apoptosis in pleomorphic adenoma. (PMID:23332881)
• Aortic protection in diabetes by zinc supplementation is associated with upregulation of both metallothionein and Nrf2 expression. (PMID:23536959)
• we found that metallothionein expression induced by Cd occurred much later, with the expression seen at least 12h or more after the Nrf2-dependent immediate responses were almost completed. (PMID:24440467)

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), MT1H (ENSG00000205358), MT1A (ENSG00000205362), MT1M (ENSG00000205364), MT1HL1 (ENSG00000244020)

Protein

Protein identifiers

Metallothionein-1F — P04733 (reviewed: P04733)

Alternative names: Metallothionein-IF

All UniProt accessions (2): P04733, H3BRY8

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 (2): NP_001288201, NP_005940* (*=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-P04733-F1	79.50	0.01

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: 225 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_RESPONSE_TO_ZINC_ION, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_CELLULAR_RESPONSE_TO_CADMIUM_ION, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_GROWTH, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_RESPONSE_TO_COPPER_ION, IIZUKA_LIVER_CANCER_PROGRESSION_L1_G1_UP, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP

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
MT1F	NQO1	P15559	691
MT1F	PLA2G2A	P14555	641
MT1F	APRT	P07741	561
MT1F	GSR	P00390	533
MT1F	SLC30A1	Q9Y6M5	524
MT1F	HMOX1	P09601	469
MT1F	PTPN1	P18031	424
MT1F	ATP7B	P35670	390
MT1F	MT1H	P80294	384
MT1F	MT1G	P13640	381
MT1F	MTF1	Q14872	379
MT1F	MT1M	Q8N339	374
MT1F	EPCAM	P16422	352
MT1F	MAP1S	Q66K74	349
MT1F	LEFTY2	O00292	348

IntAct

11 interactions, top by confidence:

A	B	Type	Score
NOP2	MT1F	psi-mi:“MI:0915”(physical association)	0.560
MT1F	NOP2	psi-mi:“MI:0915”(physical association)	0.560
MT1F	E6	psi-mi:“MI:0915”(physical association)	0.370
MT1F	E7	psi-mi:“MI:0915”(physical association)	0.370
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
MT1F	ERI3	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): NOP2 (Two-hybrid), PLCG1 (Affinity Capture-MS), RPRD1A (Affinity Capture-MS), ERI3 (Affinity Capture-MS), WDR45B (Affinity Capture-MS), GNB1L (Affinity Capture-MS), KLHL42 (Affinity Capture-MS), MT1F (Proximity Label-MS), MT1F (Affinity Capture-MS), MT1F (Two-hybrid), MT1F (Two-hybrid), MT1F (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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

827 predictions. Top by Δscore:

Variant	Effect	Δscore
16:56658671:GCAGG:G	acceptor_loss	1.0000
16:56658672:CAG:C	acceptor_loss	1.0000
16:56658673:A:AG	acceptor_gain	1.0000
16:56658673:AGG:A	acceptor_loss	1.0000
16:56658674:G:GA	acceptor_gain	1.0000
16:56658674:GGT:G	acceptor_gain	1.0000
16:56658736:GAAGA:G	donor_gain	1.0000
16:56658738:AGA:A	donor_gain	1.0000
16:56658739:GA:G	donor_gain	1.0000
16:56658739:GAG:G	donor_gain	1.0000
16:56658741:G:GG	donor_gain	1.0000
16:56658745:GT:G	donor_gain	1.0000
16:56659187:GAT:G	donor_gain	1.0000
16:56658083:GCTG:G	donor_gain	0.9900
16:56658087:G:GG	donor_gain	0.9900
16:56658670:C:A	acceptor_gain	0.9900
16:56658673:AG:A	acceptor_gain	0.9900
16:56658673:AGGT:A	acceptor_gain	0.9900
16:56658674:GG:G	acceptor_gain	0.9900
16:56658674:GGTG:G	acceptor_gain	0.9900
16:56658674:GGTGT:G	acceptor_gain	0.9900
16:56658736:G:GT	donor_gain	0.9900
16:56658737:AAGA:A	donor_gain	0.9900
16:56658033:A:T	donor_gain	0.9800
16:56658084:CTGGT:C	donor_loss	0.9800
16:56658086:GGT:G	donor_loss	0.9800
16:56658087:G:T	donor_loss	0.9800
16:56658088:T:A	donor_loss	0.9800
16:56658093:A:T	donor_gain	0.9800
16:56658672:CA:C	acceptor_loss	0.9800

AlphaMissense

401 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:56659089:C:G	C37W	0.867
16:56659087:T:C	C37R	0.825
16:56659087:T:A	C37S	0.820
16:56659088:G:C	C37S	0.820
16:56659086:C:G	C36W	0.818
16:56659084:T:C	C36R	0.810
16:56658722:T:C	C26R	0.809
16:56659080:C:G	C34W	0.807
16:56659158:C:G	C60W	0.806
16:56659108:T:A	C44S	0.805
16:56659109:G:C	C44S	0.805
16:56658689:T:C	C15R	0.802
16:56659101:T:G	C41W	0.802
16:56659120:T:A	C48S	0.799
16:56659121:G:C	C48S	0.799
16:56659110:T:G	C44W	0.795
16:56659128:C:G	C50W	0.782
16:56658683:T:C	C13R	0.780
16:56659120:T:C	C48R	0.780
16:56658724:C:G	C26W	0.774
16:56658073:C:G	C5W	0.773
16:56659122:T:G	C48W	0.773
16:56659155:C:G	C59W	0.771
16:56658691:C:G	C15W	0.770
16:56659126:T:A	C50S	0.770
16:56659127:G:C	C50S	0.770
16:56659149:C:G	C57W	0.767
16:56659126:T:C	C50R	0.766
16:56658701:T:C	C19R	0.759
16:56659077:C:G	C33W	0.757

dbSNP variants (sampled 300 via entrez): RS1000517726 (16:56658714 A>C,G), RS1002132174 (16:56656037 A>T), RS1003404004 (16:56657442 G>T), RS1005044839 (16:56658353 T>C), RS1007635601 (16:56656646 T>G), RS1008889945 (16:56658006 C>T), RS1011336382 (16:56656071 C>G,T), RS1013015211 (16:56657471 T>C), RS1015032613 (16:56659668 C>T), RS1015415581 (16:56659360 G>A,C), RS1016095877 (16:56656360 C>A,G,T), RS1016164453 (16:56656647 G>A), RS1019949434 (16:56659019 G>A,C), RS1020004245 (16:56656076 C>A,T), RS1021649836 (16:56657239 C>T)

Disease associations

OMIM: gene MIM:156352 | 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
GCST000175_9	Height	7.000000e-07
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

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

Chemical	Actions (top 5)	PubMed papers
Cadmium	decreases reaction, increases expression, increases abundance, affects cotreatment	14
Cadmium Chloride	increases abundance, increases reaction, affects cotreatment, decreases reaction, increases expression (+2 more)	13
sodium arsenite	affects cotreatment, decreases reaction, increases expression, affects binding, increases abundance	9
Valproic Acid	affects cotreatment, increases expression, affects expression	9
Arsenic Trioxide	decreases expression, increases expression	8
Particulate Matter	decreases expression, decreases reaction, increases abundance, increases expression, affects cotreatment	6
Copper	affects binding, decreases expression, increases expression	5
Estradiol	increases expression, affects cotreatment, decreases expression	5
Silver	increases expression	5
Zinc	affects cotreatment, increases expression	5
Benzo(a)pyrene	decreases expression	4
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	4
Arsenic	increases abundance, increases expression, affects cotreatment	3
Cisplatin	affects expression, affects cotreatment, increases expression, affects response to substance	3
Cyclosporine	increases expression	3
Zinc Sulfate	increases expression	3
bisphenol A	affects expression, decreases expression	2
lead acetate	decreases expression, increases expression	2
zinc chloride	increases reaction, increases expression	2
cupric chloride	decreases expression, increases expression, increases reaction	2
nickel sulfate	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
motexafin gadolinium	affects reaction, increases expression	2
Temozolomide	affects response to substance, decreases expression	2
Acetylcysteine	affects cotreatment, decreases reaction, increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Amiodarone	increases expression	2
Cannabidiol	increases expression, affects cotreatment	2
Disulfiram	increases expression, increases reaction, affects binding, decreases expression	2
Nickel	increases expression	2

Clinical trials (associated diseases)

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