MT3 (Metallothionein 3)

A neuronal growth inhibitory factor involved in zinc homeostasis and neurodegeneration

Gene Information Card

Symbol MT3
Full Name Metallothionein 3
Gene Type protein-coding
Chromosomal Location 16q13
NCBI Gene ID 4504 ncbi.nlm.nih.gov/gene/4504
Ensembl ID ENSG00000187134
UniProt ID P25713
OMIM ID 139255
HGNC ID 7433
Aliases GIF, GIFB, ZnMT3

Description

MT3 encodes metallothionein 3, a cysteine-rich protein that binds heavy metals such as zinc and copper. It is primarily expressed in the brain and acts as a growth inhibitory factor (GIF) for neurons. MT3 plays a key role in zinc homeostasis, protection against oxidative stress, and regulation of neuronal survival. Dysregulation of MT3 is implicated in Alzheimer disease and other neurodegenerative disorders.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Alzheimer Disease Reduced MT3 expression leads to impaired zinc buffering and increased amyloid-beta aggregation, contributing to neurotoxicity. PMID: 10428034, 15689449
Amyotrophic Lateral Sclerosis Altered MT3 levels in spinal cord motor neurons may affect zinc homeostasis and oxidative stress response. PMID: 15987639
Brain Neoplasms MT3 expression is downregulated in glioblastoma, potentially affecting tumor growth and invasion. PMID: 19177216

Expression Profile

Tissue Expression
Tissue nTPM level
Brain 12.5 High
Testis 2.1 Low
Kidney 1.8 Low
Liver 0.5 Not detected
Heart 0.3 Not detected
Cell Line Expression
Cell Line nTPM Notes
SH-SY5Y (neuroblastoma) 8.4 Neuronal model; high MT3 expression
U-87 MG (glioblastoma) 1.2 Low expression compared to normal brain
HEK293 (embryonic kidney) 0.6 Very low endogenous expression
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.1A>G (p.Met1Val) missense <0.01% Start codon loss; predicted loss of function
c.205C>T (p.Arg69Cys) missense <0.01% Alters zinc-binding capacity; associated with altered neuronal growth inhibition
Mutation functional classification

Loss of Function (LOF)

Mutations affecting start codon or zinc-binding cysteines reduce MT3's ability to sequester zinc, leading to impaired neuroprotection.

Gain of Function (GOF)

Not described in literature.

Dominant Negative (DN)

Not described in literature.

Pathways

• Metallothionein bind metals (REACT_25056)
• Zinc homeostasis (REACT_25057)

Protein Summary

Metallothionein 3 (MT3) is a 68-amino acid protein with 20 cysteine residues that coordinate 7 zinc ions. It is predominantly expressed in the brain, particularly in astrocytes and neurons. MT3 inhibits neuronal growth and protects against zinc-mediated neurotoxicity. Its expression is reduced in Alzheimer disease brains, contributing to amyloid plaque formation and oxidative damage.

Related Products

Product name Cat.No. Species Gene ID
MT3 Knockout HEK293 Cell Line EDJ-KQ5250 Human 4504 Details Get a Quote
MT3 Knockout HeLa Cell Line EDJ-KQ53915 Human 4504 Details Get a Quote
MT3 Knockout A-549 Cell Line EDJ-KQ62408 Human 4504 Details Get a Quote
MT3 Knockout HCT 116 Cell Line EDJ-KQ70875 Human 4504 Details Get a Quote
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