MT3
protein-codingmetallothionein 3, the group of Metallothioneins
Gene summary
This gene is a member of the metallothionein family of genes. Proteins encoded by this gene family are low in molecular weight, are cysteine-rich, lack aromatic residues, and bind divalent heavy metal ions. This gene family member displays tissue-specific expression, and contains a threonine insert near its N-terminus and a glutamate-rich hexapeptide insert near its C-terminus relative to the proteins encoded by other gene family members. It plays an important role in zinc and copper homeostasis, and is induced under hypoxic conditions. The encoded protein is a growth inhibitory factor, and reduced levels of the protein are observed in the brains of individuals with some metal-linked neurodegenerative disorders such as Alzheimer's disease. [provided by RefSeq, Sep 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MT3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005954.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 9 | 1 | 10 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 9 | 1 | 1 | 11 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005945.1 | 3 | MANE Select | |
| Ensembl | ENSP00000200691.5 | 3 | MANE Select | |
| Ensembl | ENSP00000455353.1 | 4 | Standard | |
| Ensembl | ENSP00000455980.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Copper homeostasis
- Zinc homeostasis
- Response to metal ions
- Cellular responses to external stimuli
- Metallothioneins bind metals
Biological Process
- obsolete protein import into nucleus, translocation
- response to hypoxia
- positive regulation of protein phosphorylation
- energy reserve metabolic process
- cholesterol catabolic process
Molecular Function
- copper ion binding
- protein binding
- drug binding
- zinc ion binding
- antioxidant activity
Cellular Component
- extracellular space
- nucleus
- cytoplasm
- mitochondrial outer membrane
- rough endoplasmic reticulum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000200691
- Coding exons
- 3
- Length
- 2015
- Individuals with no LoFs
- 125706
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125712
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.661 | 26 | 37.4 | 0.696 | 0.00000176 | 443 |
| Missense (PolyPhen) | 8 | 11.706 | 0.68344 | 148 | ||
| Synonymous | -0.587 | 17 | 14.2 | 1.20 | 7.87e-7 | 106 |
| Loss of Function | 0.869 | 2 | 3.84 | 0.521 | 1.61e-7 | 48 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.0000090 | 0.0000088 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds heavy metals. Contains three zinc and three copper atoms per polypeptide chain and only a negligible amount of cadmium. Inhibits survival and neurite formation of cortical neurons in vitro.;
Recessive Scores
- pRec
- 0.260
Intolerance Scores
- LoFtool
- 0.625
- RVIS EVS
- 0.32
- RVIS percentile EVS
- 72.94
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.307
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |