Details for: MYOZ2

Gene ID: 51778

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: MYOZ2

Ensembl ID: ENSG00000172399

Description: myozenin 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • cardiac muscle cell CL0000746
    CSI 61.3
    rCSI 87.97%
    PRS 99.31
  • regular atrial cardiac myocyte CL0002129
    CSI 23.8
    rCSI 76.6%
    PRS 99.6
  • ventricular cardiac muscle cell CL2000046
    CSI 21.81
    rCSI 74.7%
    PRS 99.91
  • ependymal cell CL0000065
    CSI 16.5
    rCSI 33.49%
    PRS 98.39
  • fibroblast of cardiac tissue CL0002548
    CSI 14.44
    rCSI 69.19%
    PRS 99.95
  • cardiac endothelial cell CL0010008
    CSI 13.72
    rCSI 55.35%
    PRS 99.92
  • endocardial cell CL0002350
    CSI 12.73
    rCSI 60.96%
    PRS 99.7
  • regular ventricular cardiac myocyte CL0002131
    CSI 12.52
    rCSI 78.2%
    PRS 99.44
  • fibroblast CL0000057
    CSI 11.57
    rCSI 33.27%
    PRS 99.05
  • pericyte CL0000669
    CSI 8.23
    rCSI 21.92%
    PRS 95.32
  • muscle cell CL0000187
    CSI 7.68
    rCSI 15.76%
    PRS 99.27
  • Schwann cell CL0002573
    CSI 7.27
    rCSI 20.67%
    PRS 99.68
  • mesothelial cell CL0000077
    CSI 6.48
    rCSI 25.35%
    PRS 98.98
  • epicardial adipocyte CL1000309
    CSI 6.43
    rCSI 20.93%
    PRS 99.6
  • adipocyte CL0000136
    CSI 4.5
    rCSI 5.78%
    PRS 99.49
  • cell of skeletal muscle CL0000188
    CSI 3.77
    rCSI 40.97%
    PRS 98.63
  • slow muscle cell CL0000189
    CSI 2.21
    rCSI 29.4%
    PRS 97.83

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.

Comma-separated if multiple.
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)

Loading network (please wait)...

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 [MYOZ2](/details-gene/51778) (myozenin 2) is a protein-coding gene located on chromosome 4q26 that plays a critical role in muscle-cell architecture and signaling. It functions primarily as a structural component of the sarcomere's Z-disc, where it anchors actin filaments and interacts with other Z-disc proteins to maintain sarcomeric integrity. This is consistent with initial characterizations of the gene, then named C4orf5, which identified its specific expression in cardiac and skeletal muscle ([Link](https://doi.org/10.1006/geno.2000.6399)). Beyond its structural role, [MYOZ2](/details-gene/51778) is also a key negative regulator of the calcineurin-NFAT signaling cascade, a pathway central to cardiac hypertrophy. Expression data confirms its profound significance in [cardiac muscle cell](/details-cell/CL0000746)s. Clinically, mutations in [MYOZ2](/details-gene/51778) have been identified as a cause of hypertrophic cardiomyopathy, highlighting its essential function in normal heart physiology ([Link](https://doi.org/10.1161/01.res.0000263008.66799.aa)). ## Cellular Roles and Expression Landscape The expression profile of [MYOZ2](/details-gene/51778) underscores its specialized function within muscle tissues, particularly the heart. **Overall**, the gene exhibits its highest significance in [cardiac muscle cell](/details-cell/CL0000746) (CSI: 61.30), with exceptionally strong signals in specific subtypes such as [regular atrial cardiac myocyte](/details-cell/CL0002129) and [ventricular cardiac muscle cell](/details-cell/CL2000046). This robust and specific expression pattern establishes [MYOZ2](/details-gene/51778) as a defining marker and a crucial functional component of cardiomyocytes. Its high significance extends to other cells within the cardiac microenvironment, including [fibroblast of cardiac tissue](/details-cell/CL0002548), [cardiac endothelial cell](/details-cell/CL0010008), and [pericyte](/details-cell/CL0000669), suggesting a broader role in maintaining cardiac tissue structure and homeostasis beyond the myocyte itself. The presence in generalized [muscle cell](/details-cell/CL0000187)s is consistent with its known role in skeletal muscle as well. The data strongly indicate that [MYOZ2](/details-gene/51778) is a cornerstone protein for the structural and functional integrity of the heart. ## Pathways and Molecular Function Functional annotation reveals the dual structural and regulatory roles of [MYOZ2](/details-gene/51778). As a structural protein, its localization is firmly established within the [Sarcomere](/details-cell/GO:0030017) and specifically at the [Z disc](/details-cell/GO:0030018). Its molecular functions, including [Actin binding](/details-cell/GO:0003779), support its role in the biological process of [Sarcomere organization](/details-cell/GO:0045214). It interacts with a network of other Z-disc proteins, as evidenced by its binding capabilities with telethonin ([Telethonin binding](/details-cell/GO:0031433)) and FATZ ([Fatz binding](/details-cell/GO:0051373)), which is critical for tethering the contractile apparatus ([Link](https://doi.org/10.1242/jcs.02484), [Link](https://doi.org/10.1074/jbc.m200712200)). From a regulatory standpoint, [MYOZ2](/details-gene/51778) is involved in the [Negative regulation of calcineurin-nfat signaling cascade](/details-cell/GO:0070885). This is mediated through its direct interaction with calcineurin ([Protein phosphatase 2b binding](/details-cell/GO:0030346)), a key enzyme in the signaling pathway that drives pathological cardiac growth ([Link](https://doi.org/10.1073/pnas.260501097)). This function links the mechanical state of the sarcomere directly to intracellular growth signaling pathways, positioning [MYOZ2](/details-gene/51778) as a critical mechanosensor and signaling hub. ## Research Directions The established link between [MYOZ2](/details-gene/51778), sarcomere function, and hypertrophic cardiomyopathy provides a clear path for further investigation. **Proposed Hypotheses:** 1. Pathogenic mutations in [MYOZ2](/details-gene/51778) linked to hypertrophic cardiomyopathy primarily disrupt its inhibitory interaction with calcineurin, leading to disinhibition of the NFAT signaling pathway and subsequent pathological cardiomyocyte growth, rather than causing a primary structural failure of the Z-disc. 2. In cardiac fibroblasts, [MYOZ2](/details-gene/51778) expression is dynamically regulated in response to cardiac stress or injury, and its downregulation may contribute to adverse cardiac remodeling by altering fibroblast mechanosensing and activation. **Experimental Approach:** To test the first hypothesis, one could utilize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Pathogenic [MYOZ2](/details-gene/51778) mutations identified in patients with hypertrophic cardiomyopathy would be introduced into hiPSC-CMs using CRISPR-Cas9 gene editing. These edited cells, along with isogenic controls, would be subjected to mechanical or neurohormonal stress. The primary readouts would be the quantification of NFAT nuclear translocation via immunofluorescence and the measurement of hypertrophic marker genes (e.g., *NPPA*, *NPPB*) by qRT-PCR. Co-immunoprecipitation assays in these cell models could directly assess whether the mutations impair the physical binding between MYOZ2 and calcineurin. **Therapeutic Potential:** As an intracellular structural protein essential for normal cardiac function, [MYOZ2](/details-gene/51778) is not a suitable target for conventional pharmacological inhibition or activation, as this would likely lead to severe cardiotoxicity. The therapeutic potential for diseases caused by [MYOZ2](/details-gene/51778) mutations lies in the realm of gene therapy. A strategy involving adeno-associated virus (AAV)-mediated delivery of a correct copy of the [MYOZ2](/details-gene/51778) gene to cardiomyocytes could potentially restore normal protein function and halt or reverse disease progression in patients with inherited cardiomyopathy. This approach would aim to correct the underlying genetic defect rather than modulating the protein's activity.

Genular Protein ID: 2364269974

Symbol: MYOZ2_HUMAN

Name: Myozenin-2

UniProtKB Accession Codes:

Q9NPC6 O43415 Q9HB92

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 11 Ensembl 1 GO 12 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11161785

Title: Identification and characterization of a novel gene (C4orf5) located on human chromosome 4q with specific expression in cardiac and skeletal muscle.

PubMed ID: 11161785

DOI: 10.1006/geno.2000.6399

PubMed ID: 11114196

Title: Calsarcins, a novel family of sarcomeric calcineurin-binding proteins.

PubMed ID: 11114196

DOI: 10.1073/pnas.260501097

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11842093

Title: Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin family, interacts with multiple Z-disc proteins.

PubMed ID: 11842093

DOI: 10.1074/jbc.m200712200

PubMed ID: 16076904

Title: The Z-disc proteins myotilin and FATZ-1 interact with each other and are connected to the sarcolemma via muscle-specific filamins.

PubMed ID: 16076904

DOI: 10.1242/jcs.02484

PubMed ID: 17347475

Title: Myozenin 2 is a novel gene for human hypertrophic cardiomyopathy.

PubMed ID: 17347475

DOI: 10.1161/01.res.0000263008.66799.aa

Sequence Information:

  • Length: 264
  • Mass: 29898
  • Checksum: 8636AEF79A6F8916
  • Sequence:
    • MLSHNTMMKQ RKQQATAIMK EVHGNDVDGM DLGKKVSIPR DIMLEELSHL SNRGARLFKM 
RQRRSDKYTF ENFQYQSRAQ INHSIAMQNG KVDGSNLEGG SQQAPLTPPN TPDPRSPPNP 
DNIAPGYSGP LKEIPPEKFN TTAVPKYYQS PWEQAISNDP ELLEALYPKL FKPEGKAELP 
DYRSFNRVAT PFGGFEKASR MVKFKVPDFE LLLLTDPRFM SFVNPLSGRR SFNRTPKGWI 
SENIPIVITT EPTDDTTVPE SEDL