Details for: MTX3

Gene ID: 345778

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: MTX3

Ensembl ID: ENSG00000177034

Description: metaxin 3

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • ionocyte CL0005006
    CSI 3.62
    rCSI 3.88%
    PRS 98.87
  • ciliated epithelial cell CL0000067
    CSI 3.27
    rCSI 2.88%
    PRS 95.63
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.96
    rCSI 5.22%
    PRS 95.44
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.88
    rCSI 3.44%
    PRS 95.43
  • multi-ciliated epithelial cell CL0005012
    CSI 2.85
    rCSI 2.85%
    PRS 96.61
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.52
    rCSI 5.65%
    PRS 95.49
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.29
    rCSI 2.85%
    PRS 94.83
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.27
    rCSI 2.93%
    PRS 96.04
  • retinal cone cell CL0000573
    CSI 2.25
    rCSI 3.63%
    PRS 95.74
  • cerebral cortex neuron CL0010012
    CSI 2.23
    rCSI 9.11%
    PRS 95.2
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.67
    rCSI 2.81%
    PRS 95.71
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.36
    rCSI 4.88%
    PRS 94.63
  • neural progenitor cell CL0011020
    CSI 1.32
    rCSI 5.81%
    PRS 93.65
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.22
    rCSI 2.96%
    PRS 94.22
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.84
    rCSI 3.16%
    PRS 94.93
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.58
    rCSI 3.39%
    PRS 95.08
  • direct pathway medium spiny neuron CL4023026
    CSI 0.47
    rCSI 11.21%
    PRS 93.54
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.44
    rCSI 10.62%
    PRS 93.18

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [MTX3](/details-gene/345778) (metaxin 3) is a protein-coding gene located on chromosome 5q14.1. Functional annotations strongly link [MTX3](/details-gene/345778) to mitochondrial biology, specifically in processes such as '[Inner mitochondrial membrane organization](/details-ontology/GO:0007007)' and '[Protein transport](/details-ontology/GO:0015031)'. It is a known component of the mitochondrial intermembrane space bridging (MIB) complex and the sorting and assembly machinery (SAM) complex, which are critical for mitochondrial structure and protein import ([Link](https://doi.org/10.1016/j.bbamcr.2015.10.009)). **Overall**, expression data reveals that [MTX3](/details-gene/345778) shows the highest significance in metabolically demanding cell types, including specialized epithelial cells like [ionocytes](/details-cell/CL0005006) and [ciliated epithelial cells](/details-cell/CL0000067), as well as a wide array of neurons within the cerebral cortex. This suggests a crucial role in maintaining mitochondrial health and function in cells with high energy and protein turnover requirements. ## Cellular Roles and Expression Landscape The expression profile of [MTX3](/details-gene/345778) highlights its importance in distinct, high-energy-demand cellular contexts. **Overall**, the gene's most significant expression is observed in specialized epithelial cells and neurons. It is a top marker for [ionocytes](/details-cell/CL0005006) (CSI: 3.62) and [ciliated epithelial cells](/details-cell/CL0000067) (CSI: 3.27), cell types that rely heavily on mitochondrial ATP production for active ion transport and ciliary motility, respectively. Beyond epithelial tissues, [MTX3](/details-gene/345778) demonstrates a broad and significant role across the central nervous system. It is highly expressed in numerous subtypes of cortical neurons, including various GABAergic interneurons such as [caudal ganglionic eminence derived cortical interneurons](/details-cell/CL4023064) (CSI: 2.96), [VIP GABAergic cortical interneurons](/details-cell/CL4023016) (CSI: 2.88), and [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) (CSI: 2.29). Its significance is also noted in glutamatergic neurons, such as [L5 extratelencephalic projecting glutamatergic cortical neurons](/details-cell/CL4023041) (CSI: 1.36). This widespread expression across diverse neuronal populations suggests a fundamental role in supporting the high metabolic demands of neuronal signaling, synaptic transmission, and cellular homeostasis within the brain. The consistent presence in both excitatory and inhibitory neurons indicates its function is likely a core component of general neuronal mitochondrial health rather than being specific to a particular neurotransmitter system. ## Pathways and Molecular Function The functions of [MTX3](/details-gene/345778) are tightly coupled to mitochondrial architecture and logistics. Gene Ontology annotations place it centrally in '[Mitochondrion organization](/details-ontology/GO:0007005)' and specifically in '[Inner mitochondrial membrane organization](/details-ontology/GO:0007007)'. This is consistent with its role as a component of the '[Mib complex](/details-ontology/GO:0140275)' and the '[Sam complex](/details-ontology/GO:0001401)', which are essential for maintaining the structure of mitochondrial cristae and for the import and assembly of beta-barrel proteins into the outer mitochondrial membrane ([Link](https://doi.org/10.1016/j.bbamcr.2015.10.009)). The gene's involvement in '[Protein transport](/details-ontology/GO:0015031)' is a key aspect of its molecular function, ensuring that newly synthesized proteins destined for the mitochondria are correctly imported and integrated. This function is vital for the cells where [MTX3](/details-gene/345778) is most highly expressed, such as neurons and ciliated cells, which require constant renewal of mitochondrial proteins to sustain their high metabolic activity. Its cellular location is primarily documented as the '[Mitochondrion](/details-ontology/GO:0005739)' and the '[Cytoplasm](/details-ontology/GO:0005737)', reflecting the journey of the protein itself from synthesis to its final destination in the mitochondrial machinery. ## Research Directions The specific expression pattern and established molecular function of [MTX3](/details-gene/345778) suggest several avenues for future research, particularly concerning its role in cellular homeostasis and disease. **Proposed Hypotheses:** 1. **Neuronal Vulnerability:** Given its high expression across multiple cortical neuron types, it is hypothesized that dysfunction or downregulation of [MTX3](/details-gene/345778) could be a contributing factor to neurodegenerative disorders characterized by mitochondrial deficits. Loss of [MTX3](/details-gene/345778) may impair mitochondrial protein import, leading to compromised energy production, oxidative stress, and ultimately neuronal death, particularly in highly active neurons. 2. **Ciliopathy and Epithelial Dysfunction:** The prominent expression in [ciliated epithelial cells](/details-cell/CL0000067) suggests a role in ciliopathies. It is hypothesized that [MTX3](/details-gene/345778) is essential for providing the localized ATP required for dynein motor activity and ciliary beating. Mutations in [MTX3](/details-gene/345778) could therefore lead to defects in mucociliary clearance or other cilia-dependent physiological processes. **Experimental Approach:** To test the hypothesis regarding neuronal vulnerability, a compelling experiment would be to generate a conditional knockout of [MTX3](/details-gene/345778) in mouse cortical neurons. Using a Cre-Lox system with a neuron-specific promoter (e.g., CamKIIa-Cre), one could delete [MTX3](/details-gene/345778) post-developmentally. The resulting phenotype could be assessed using a combination of techniques: transmission electron microscopy to analyze mitochondrial ultrastructure and cristae morphology, in vivo two-photon imaging to monitor mitochondrial dynamics and health (e.g., using reporters like Mito-RFP), and electrophysiology to measure synaptic function and neuronal firing properties. This would directly link [MTX3](/details-gene/345778) function to mitochondrial integrity and neuronal health in a physiological context. **Therapeutic Potential:** As a fundamental component of mitochondrial machinery, [MTX3](/details-gene/345778) is unlikely to be a conventional therapeutic target for inhibition, as this would likely cause significant toxicity in healthy, high-energy tissues like the brain and heart. However, if loss-of-function mutations in [MTX3](/details-gene/345778) are identified as the cause of a specific mitochondrial disease or neuropathy, it could become a target for activation or gene replacement therapies. The development of small molecules that stabilize the MIB/SAM complexes or enhance their function could offer a therapeutic strategy for diseases stemming from impaired mitochondrial protein import.

Genular Protein ID: 1256296964

Symbol: MTX3_HUMAN

Name: Metaxin-3

UniProtKB Accession Codes:

Q5HYI7 B4DL65 E9PB57 Q7Z380 Q8NB92

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 3 GO 6 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 RefSeq 3 SFLD 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 26477565

Title: Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex.

PubMed ID: 26477565

DOI: 10.1016/j.bbamcr.2015.10.009

Sequence Information:

  • Length: 312
  • Mass: 35093
  • Checksum: 3B9BAB7CF64FF8EF
  • Sequence:
    • MAAPLELSCW GGGWGLPSVH SESLVVMAYA KFSGAPLKVN VIDNTWRGSR GDVPILTTED 
DMVSQPAKIL NFLRKQKYNA DYELSAKQGA DTLAYIALLE EKLLPAVLHT FWVESDNYFT 
VTKPWFASQI PFPLSLILPG RMSKGALNRI LLTRGQPPLY HLREVEAQIY RDAKECLNLL 
SNRLGTSQFF FGDTPSTLDA YVFGFLAPLY KVRFPKVQLQ EHLKQLSNLC RFCDDILSSY 
FRLSLGGISP AGQETVDANL QKLTQLVNKE SNLIEKMDDN LRQSPQLPPR KLPTLKLTPA 
EEENNSFQRL SP