| HGNC Family | Metallothioneins (MT) |
| Name | metallothionein 4 |
| Description | Predicted to enable metal ion binding activity. Predicted to be involved in several processes, including cellular response to zinc ion; detoxification of copper ion; and intracellular zinc ion homeostasis. Predicted to act upstream of or within intracellular monoatomic cation homeostasis. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA family of testis‐specific serine/threonine kinases—which include a conserved kinase composed essentially of the catalytic domain lobes (SSTK/TSSK6) and related members such as TSSK4—has emerged as a critical regulator of postmeiotic chromatin remodeling during spermiogenesis. These kinases are highly expressed in spermatids where they phosphorylate several core histones (H1, H2A, H2AX, and H3) to facilitate the histone‐to‐protamine transition that underpins chromatin condensation. Their activity is tightly regulated by molecular chaperones; for example, HSP90 (and associated proteins HSP70/HSC70) is essential for stabilizing and activating these kinases, while additional proteins such as a novel tetratricopeptide repeat–containing SSTK-interacting protein modulate kinase function. Genetic ablation or pharmacological inhibition of these enzymes in murine models leads to impaired sperm morphology, reduced motility, and ultimately male sterility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a separate line of investigation, polymorphisms in metallothionein genes—specifically variations in the MT4 isoform (MT4-216 A/G)—have been shown to influence the toxicokinetics of heavy metals such as lead. Studies indicate that individuals harboring the mutant G allele exhibit heightened susceptibility to lead toxicity, manifesting as increases in systolic blood pressure and disruptions in renal function parameters when compared with those possessing the wild-type allele. These findings suggest that MT4 plays an important role in modulating the body’s detoxification and handling of metal exposure, with potential implications for occupational health among workers exposed to lead."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nikolay A Spiridonov, Lily Wong, Patricia M Zerfas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of SSTK, a serine/threonine protein kinase essential for male fertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.10.4250-4261.2005"}], "href": "https://doi.org/10.1128/MCB.25.10.4250-4261.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15870294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15870294"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kula N Jha, Swamy K Tripurani, Gibbes R Johnson "}, {"type": "b", "children": [{"type": "t", "text": "TSSK6 is required for γH2AX formation and the histone-to-protamine transition during spermiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.202721"}], "href": "https://doi.org/10.1242/jcs.202721"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28389581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28389581"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kula N Jha, Alyssa R Coleman, Lily Wong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heat shock protein 90 functions to stabilize and activate the testis-specific serine/threonine kinases, a family of kinases essential for male fertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.400978"}], "href": "https://doi.org/10.1074/jbc.M112.400978"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23599433"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23599433"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kula N Jha, Lily Wong, Patricia M Zerfas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a novel HSP70-binding cochaperone critical to HSP90-mediated activation of small serine/threonine kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.134767"}], "href": "https://doi.org/10.1074/jbc.M110.134767"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20829357"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20829357"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Claudia Gundacker, Karl J Wittmann, Martina Kukuckova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic background of lead and mercury metabolism in a group of medical students in Austria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Environ Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.envres.2009.05.003"}], "href": "https://doi.org/10.1016/j.envres.2009.05.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19515364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19515364"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hsin-I Chen, Yu-Wen Chiu, Yu Kuei Hsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The association of metallothionein-4 gene polymorphism and renal function in long-term lead-exposed workers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Trace Elem Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12011-009-8564-x"}], "href": "https://doi.org/10.1007/s12011-009-8564-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19921116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19921116"}]}]}]}
|
| Synonyms | MT-4, MT-IV, MTIV |
| Proteins | MT4_HUMAN |
| NCBI Gene ID | 84560 |
| API | |
| Download Associations | |
| Predicted Functions |
 |
| Co-expressed Genes |
|
| Expression in Tissues and Cell Lines |
|
MT4 has 1,607 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 79 datasets.
Click the + buttons to view associations for MT4 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of MT4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of MT4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of MT4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Cell Line Gene Expression Profiles | cell lines with high or low expression of MT4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of MT4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| BioGPS Mouse Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of MT4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of MT4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| CCLE Cell Line Gene Expression Profiles | cell lines with high or low expression of MT4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of MT4 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of MT4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of MT4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of MT4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with MT4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with MT4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of MT4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with MT4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| CTD Gene-Chemical Interactions | chemicals interacting with MT4 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
| CTD Gene-Disease Associations | diseases associated with MT4 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by MT4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with MT4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with MT4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with MT4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with MT4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with MT4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at MT4 gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of MT4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of MT4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| ESCAPE Omics Signatures of Genes and Proteins for Stem Cells | PubMedIDs of publications reporting gene signatures containing MT4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GAD Gene-Disease Associations | diseases associated with MT4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
| GAD High Level Gene-Disease Associations | diseases associated with MT4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
| GDSC Cell Line Gene Expression Profiles | cell lines with high or low expression of MT4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with MT4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing MT4 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of MT4 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of MT4 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of MT4 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of MT4 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of MT4 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of MT4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving MT4 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving MT4 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving MT4 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing MT4 protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by MT4 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by MT4 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of MT4 gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of MT4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of MT4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with MT4 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of MT4 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HMDB Metabolites of Enzymes | interacting metabolites for MT4 protein from the curated HMDB Metabolites of Enzymes dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with MT4 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for MT4 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of MT4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of MT4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of MT4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of MT4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles | cell lines with MT4 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of MT4 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of MT4 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
| LOCATE Curated Protein Localization Annotations | cellular components containing MT4 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain MT4 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MiRTarBase microRNA Targets | microRNAs targeting MT4 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of MT4 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MSigDB Cancer Gene Co-expression Modules | co-expressed genes for MT4 from the MSigDB Cancer Gene Co-expression Modules dataset. | |
| MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of MT4 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
| NURSA Protein Complexes | protein complexs containing MT4 protein recovered by IP-MS from the NURSA Protein Complexes dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of MT4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving MT4 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving MT4 protein from the Wikipathways PFOCR 2024 dataset. | |
| Reactome Pathways 2024 | pathways involving MT4 protein from the Reactome Pathways 2024 dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at MT4 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of MT4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of MT4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of MT4 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of MT4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with MT4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with MT4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
| WikiPathways Pathways 2024 | pathways involving MT4 protein from the WikiPathways Pathways 2024 dataset. | |
