MT1H

Summary

MT1H (metallothionein 1H, HGNC:7400) is a protein-coding gene on chromosome 16q13, encoding Metallothionein-1H (P80294). 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. Predicted to be active in cytoplasm and nucleus.

Source: NCBI Gene 4496 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_005951

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7400
Approved symbol	MT1H
Name	metallothionein 1H
Location	16q13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205358
Ensembl biotype	protein_coding
OMIM	156354
Entrez	4496

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000332374, ENST00000569155, ENST00000868220

RefSeq mRNA: 1 — MANE Select: NM_005951 NM_005951

CCDS: CCDS10767

Canonical transcript exons

ENST00000332374 — 3 exons

Exon	Start	End
ENSE00001403818	56670898	56671129
ENSE00001699499	56669814	56669912
ENSE00001737703	56670506	56670571

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.66.

FANTOM5 (CAGE): breadth broad, TPM avg 18.7515 / max 3265.7857, expressed in 320 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154259	16.4135	278
154261	1.3479	158
154260	0.8535	147
154258	0.1124	49
154257	0.0241	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.66	gold quality
mucosa of transverse colon	UBERON:0004991	99.61	gold quality
nephron tubule	UBERON:0001231	99.52	gold quality
kidney epithelium	UBERON:0004819	99.51	gold quality
buccal mucosa cell	CL:0002336	99.48	gold quality
lateral globus pallidus	UBERON:0002476	99.46	gold quality
metanephric glomerulus	UBERON:0004736	99.46	gold quality
renal glomerulus	UBERON:0000074	99.36	gold quality
cartilage tissue	UBERON:0002418	99.26	gold quality
pericardium	UBERON:0002407	99.24	gold quality
tongue squamous epithelium	UBERON:0006919	99.18	gold quality
globus pallidus	UBERON:0001875	99.07	gold quality
olfactory bulb	UBERON:0002264	99.02	gold quality
medial globus pallidus	UBERON:0002477	99.02	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.99	gold quality
adult organism	UBERON:0007023	98.92	gold quality
tibialis anterior	UBERON:0001385	98.91	silver quality
cardia of stomach	UBERON:0001162	98.88	gold quality
type B pancreatic cell	CL:0000169	98.85	silver quality
adult mammalian kidney	UBERON:0000082	98.81	gold quality
layer of synovial tissue	UBERON:0007616	98.55	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.49	gold quality
ventral tegmental area	UBERON:0002691	98.45	gold quality
diaphragm	UBERON:0001103	98.40	silver quality
CA1 field of hippocampus	UBERON:0003881	98.39	gold quality
renal medulla	UBERON:0000362	98.33	gold quality
upper arm skin	UBERON:0004263	98.30	silver quality
synovial joint	UBERON:0002217	98.28	gold quality
substantia nigra pars compacta	UBERON:0001965	98.22	gold quality
right lobe of liver	UBERON:0001114	98.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	39789.23
E-CURD-98	yes	15346.58
E-MTAB-8221	yes	14135.06
E-MTAB-9906	yes	11241.21
E-GEOD-130473	yes	5535.79
E-MTAB-10018	yes	3271.99
E-MTAB-10283	yes	3248.18
E-MTAB-6819	yes	1014.79
E-GEOD-109979	yes	110.92
E-HCAD-9	yes	61.38
E-MTAB-10553	yes	30.42
E-MTAB-9388	yes	14.75
E-GEOD-125970	yes	9.55
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KDM5B

miRNA regulators (miRDB)

11 targeting MT1H, 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-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-4526	99.68	67.07	1136
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-3674	97.01	68.86	1171
HSA-MIR-4785	88.53	62.71	63

Literature-anchored findings (GeneRIF, showing 5)

• S-nitrosothiols react preferentially with zinc thiolate clusters through transnitrosation. (PMID:12081484)
• 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)
• 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)
• MT1H was down-regulated in renal cell carcinogenesis. (PMID:24662736)
• Results show that MT1H is downregulated in TCGA dataset and a panel of 12 paired tumor/non-tumor tissues. Ectopic overexpression of MT1H in HepG2 and Hep3B cells inhibited cell proliferation, invasion, and migration through inhibiting Wnt/beta-catenin pathway. (PMID:28241806)

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

Protein

Protein identifiers

Metallothionein-1H — P80294 (reviewed: P80294)

Alternative names: Metallothionein-0, Metallothionein-IH

All UniProt accessions (3): A0A140VJP7, P80294, H3BTC4

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_005942* (*=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-P80294-F1	78.98	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: 158 (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, BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_ZINC_ION, CHUANG_OXIDATIVE_STRESS_RESPONSE_UP, GOBP_CELLULAR_RESPONSE_TO_CADMIUM_ION, GOBP_GROWTH, KYNG_DNA_DAMAGE_DN, KYNG_DNA_DAMAGE_BY_4NQO, GOBP_RESPONSE_TO_COPPER_ION, IIZUKA_LIVER_CANCER_PROGRESSION_L1_G1_UP, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_RESPONSE_TO_METAL_ION, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_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

400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MT1H	APRT	P07741	563
MT1H	NQO1	P15559	541
MT1H	GSR	P00390	520
MT1H	PLA2G2A	P14555	515
MT1H	GPC3	P51654	447
MT1H	PTPN1	P18031	437
MT1H	SLC30A1	Q9Y6M5	434
MT1H	MTF1	Q14872	431
MT1H	CLEC4M	Q9H2X3	424
MT1H	CRHBP	P24387	423
MT1H	H3BSS0	H3BSS0	400
MT1H	ATP7B	P35670	395
MT1H	MT1F	P04733	384
MT1H	MT1X	P80297	373
MT1H	MT1A	P04731	372

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SPINK7	MT1H	psi-mi:“MI:0915”(physical association)	0.550
MT1H	SPINK7	psi-mi:“MI:0915”(physical association)	0.550
DNAJC1	MT1H	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (5): MT1H (Two-hybrid), MT1H (Two-hybrid), MT1H (Two-hybrid), MT1H (Affinity Capture-MS), MT1H (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

398 predictions. Top by Δscore:

Variant	Effect	Δscore
16:56670567:GAAGA:G	donor_gain	1.0000
16:56670569:AGA:A	donor_gain	1.0000
16:56670570:GA:G	donor_gain	1.0000
16:56670570:GAG:G	donor_gain	1.0000
16:56670572:G:GG	donor_gain	1.0000
16:56669908:GGCTG:G	donor_gain	0.9900
16:56669909:GCTG:G	donor_gain	0.9900
16:56669909:GCTGG:G	donor_gain	0.9900
16:56669910:CTGGT:C	donor_loss	0.9900
16:56669911:TGGTA:T	donor_loss	0.9900
16:56669913:G:C	donor_loss	0.9900
16:56669913:G:GG	donor_gain	0.9900
16:56669914:T:A	donor_loss	0.9900
16:56669919:A:T	donor_gain	0.9900
16:56670501:TGCAG:T	acceptor_loss	0.9900
16:56670502:GCAGG:G	acceptor_loss	0.9900
16:56670503:CA:C	acceptor_loss	0.9900
16:56670504:A:AG	acceptor_gain	0.9900
16:56670504:A:C	acceptor_loss	0.9900
16:56670504:AG:A	acceptor_gain	0.9900
16:56670504:AGGT:A	acceptor_gain	0.9900
16:56670505:G:A	acceptor_loss	0.9900
16:56670505:G:GG	acceptor_gain	0.9900
16:56670505:GG:G	acceptor_gain	0.9900
16:56670505:GGT:G	acceptor_gain	0.9900
16:56670505:GGTG:G	acceptor_gain	0.9900
16:56670568:AAGA:A	donor_gain	0.9900
16:56670570:GAGTG:G	donor_loss	0.9900
16:56670571:AG:A	donor_loss	0.9900
16:56670572:GTGA:G	donor_loss	0.9900

AlphaMissense

398 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:56670914:C:G	C37W	0.775
16:56670905:C:G	C34W	0.758
16:56670935:T:G	C44W	0.740
16:56670911:T:G	C36W	0.734
16:56670912:T:C	C37R	0.732
16:56670909:T:C	C36R	0.727
16:56670520:T:C	C15R	0.717
16:56670553:T:C	C26R	0.716
16:56670933:T:A	C44S	0.716
16:56670934:G:C	C44S	0.716
16:56669899:C:G	C5W	0.715
16:56670926:T:G	C41W	0.715
16:56670514:T:C	C13R	0.714
16:56670902:C:G	C33W	0.712
16:56670903:T:C	C34R	0.707
16:56670974:C:G	C57W	0.705
16:56670555:C:G	C26W	0.700
16:56670912:T:A	C37S	0.698
16:56670913:G:C	C37S	0.698
16:56670945:T:C	C48R	0.698
16:56670532:T:C	C19R	0.684
16:56670953:C:G	C50W	0.683
16:56670947:C:G	C48W	0.680
16:56670980:C:G	C59W	0.679
16:56670945:T:A	C48S	0.675
16:56670946:G:C	C48S	0.675
16:56670983:T:G	C60W	0.675
16:56670933:T:C	C44R	0.673
16:56670516:C:G	C13W	0.665
16:56670522:C:G	C15W	0.665

dbSNP variants (sampled 300 via entrez): RS1000231292 (16:56669234 G>A), RS1000260807 (16:56669429 T>C), RS1001901098 (16:56670227 G>A), RS1004767919 (16:56668896 T>C), RS1005246617 (16:56669162 C>A), RS1006499248 (16:56670124 G>A), 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), RS1019207626 (16:56669295 G>A)

Disease associations

OMIM: gene MIM:156354 | 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

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

Chemical	Actions (top 5)	PubMed papers
Cadmium	increases abundance, increases expression	10
Valproic Acid	affects cotreatment, increases expression	7
sodium arsenite	increases expression	5
Silver	increases expression	5
Arsenic Trioxide	affects binding, decreases reaction, increases expression	4
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	4
Zinc	affects cotreatment, increases expression	4
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	3
Aflatoxin B1	decreases methylation, increases expression	3
Cadmium Chloride	increases abundance, increases expression	3
Zinc Sulfate	increases expression	3
Copper Sulfate	decreases expression, increases expression	3
zinc chloride	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
motexafin gadolinium	increases reaction, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Cisplatin	affects expression, decreases expression, increases response to substance	2
Copper	increases expression, affects binding	2
Parathion	increases methylation, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	increases expression	2
Silver Nitrate	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Vitamin K 3	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
GSK-J4	increases expression	1
ML385	decreases reaction, increases expression	1
methylmercuric chloride	increases expression	1
lead acetate	increases expression	1

Clinical trials (associated diseases)

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