Details for: MYCN

Gene ID: 4613

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: MYCN

Ensembl ID: ENSG00000134323

Description: MYCN proto-oncogene, bHLH transcription factor

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • hematopoietic precursor cell CL0008001
    CSI 6.3
    rCSI 6.48%
    PRS 99.12
  • neural crest cell CL0011012
    CSI 3.58
    rCSI 2.83%
    PRS 97.17
  • epithelial cell CL0000066
    CSI 3.15
    rCSI 4.84%
    PRS 92.98
  • extravillous trophoblast CL0008036
    CSI 2.85
    rCSI 3.53%
    PRS 97.7
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.49
    rCSI 2.25%
    PRS 98.27
  • radial glial cell CL0000681
    CSI 2.46
    rCSI 3.42%
    PRS 98.24
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.41
    rCSI 3.1%
    PRS 97.38
  • placental villous trophoblast CL2000060
    CSI 2.33
    rCSI 3.59%
    PRS 97.62
  • syncytiotrophoblast cell CL0000525
    CSI 1.94
    rCSI 5.59%
    PRS 97.25
  • endothelial cell of lymphatic vessel CL0002138
    CSI 1.9
    rCSI 3.77%
    PRS 97.88
  • hematopoietic multipotent progenitor cell CL0000837
    CSI 1.31
    rCSI 3.16%
    PRS 99.38

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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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • 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 [MYCN](/details-gene/4613) is a proto-oncogene that encodes the N-myc protein, a basic helix-loop-helix (bHLH) transcription factor crucial for regulating gene expression. As a nuclear protein, it functions primarily through [Dna-binding transcription factor activity](/details-ontology/GO:0003700) and [Protein dimerization activity](/details-ontology/GO:0046983), modulating both positive and negative transcriptional programs. Expression data indicates its significant role in developmental processes, with the highest significance observed in progenitor and precursor cell populations, including [hematopoietic precursor cell](/details-cell/CL0008001) and [neural crest cell](/details-cell/CL0011012). Its amplification and overexpression are strongly associated with several cancers, most notably neuroblastoma ([164840](https://omim.org/entry/164840)), highlighting its critical role in controlling cell proliferation and differentiation. ## Cellular Roles and Expression Landscape The expression profile of [MYCN](/details-gene/4613) underscores its fundamental role in undifferentiated and rapidly proliferating cell types, consistent with its function as a proto-oncogene. **Overall**, the gene shows the highest significance in developmental precursor populations across multiple lineages. Its most prominent role is observed in the hematopoietic system, where it is a key marker for [hematopoietic precursor cell](/details-cell/CL0008001) (CSI: 6.30), [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 2.49), and [hematopoietic multipotent progenitor cell](/details-cell/CL0000837) (CSI: 1.31). This suggests a critical function in maintaining the proliferative capacity and pluripotency of the hematopoietic stem cell pool. Concurrently, [MYCN](/details-gene/4613) is highly significant in the developing nervous system, with high CSI values in [neural crest cell](/details-cell/CL0011012) (CSI: 3.58), [radial glial cell](/details-cell/CL0000681) (CSI: 2.46), and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) (CSI: 2.41). This pattern is consistent with its established role in neurogenesis and its pathological involvement in neuroblastoma, a tumor thought to arise from the embryonic neural crest. Furthermore, [MYCN](/details-gene/4613) expression is significant in placental tissues, including [extravillous trophoblast](/details-cell/CL0008036) (CSI: 2.85) and [placental villous trophoblast](/details-cell/CL2000060) (CSI: 2.33), as well as in general [epithelial cell](/details-cell/CL0000066) populations (CSI: 3.15), reflecting its broad importance in embryonic development and tissue growth. ## Pathways and Molecular Function Functionally, [MYCN](/details-gene/4613) operates as a transcriptional regulator localized to the [Nucleus](/details-ontology/GO:0005634), particularly within the [Nucleoplasm](/details-ontology/GO:0005654) and [Chromatin](/details-ontology/GO:0000785). Its molecular activity is centered on sequence-specific DNA binding, enabling it to act as a [Dna-binding transcription activator activity, rna polymerase ii-specific](/details-ontology/GO:0001228). This function is critical for its role in biological processes such as [Positive regulation of dna-templated transcription](/details-ontology/GO:0045893) and [Negative regulation of gene expression](/details-ontology/GO:0010629), indicating its capacity to both activate and repress target genes depending on the cellular context and co-factor availability. [MYCN](/details-gene/4613) is implicated in several key signaling cascades, as evidenced by its annotation in Reactome pathways like [Signaling by receptor tyrosine kinases](/details-pathway/R-HSA-9006934) and [Signaling by alk](/details-pathway/R-HSA-201556). These pathways are essential for controlling cell growth, proliferation, and differentiation, placing [MYCN](/details-gene/4613) as a crucial downstream effector of extracellular growth signals. Its ability to engage in [Protein binding](/details-ontology/GO:0005515), including [Kinase binding](/details-ontology/GO:0019900), is central to its regulation and function, with phosphorylation by kinases like casein kinase II known to modulate its activity ([Link](https://doi.org/10.1111/j.1432-1033.1992.tb17367.x)). ## Research Directions The data solidifies the role of [MYCN](/details-gene/4613) as a master regulator in progenitor cells, with its dysregulation being a key event in oncogenesis. Its high significance in both neural and hematopoietic precursors warrants further investigation into its lineage-specific functions and mechanisms of malignant transformation. Based on its expression profile and known functions, several testable hypotheses can be proposed: 1. **Hypothesis:** Overexpression of [MYCN](/details-gene/4613) in [neural crest cell](/details-cell/CL0011012) populations during development is sufficient to induce a pre-malignant, neuroblastoma-like state by blocking terminal differentiation and promoting uncontrolled proliferation. 2. **Hypothesis:** In [hematopoietic precursor cell](/details-cell/CL0008001), [MYCN](/details-gene/4613) dysregulation disrupts normal hematopoiesis by altering the transcriptional landscape downstream of essential signaling pathways like ALK, thereby predisposing these cells to leukemic transformation. To test the first hypothesis regarding neuroblastoma initiation, a key experimental approach would be: * **Experiment:** Utilize a directed differentiation protocol to generate [neural crest cell](/details-cell/CL0011012) populations from human induced pluripotent stem cells (iPSCs). A doxycycline-inducible lentiviral vector could be used to precisely control the timing and level of [MYCN](/details-gene/4613) overexpression. The impact on cellular fate could be assessed using single-cell RNA sequencing to map differentiation trajectories and identify gene regulatory networks driven by [MYCN](/details-gene/4613). Concurrently, the tumorigenic potential of these engineered cells could be evaluated through xenograft assays in immunocompromised mice. **Therapeutic Potential:** [MYCN](/details-gene/4613) is a well-established, high-value therapeutic target, particularly for MYCN-amplified neuroblastoma. The therapeutic strategy would be **inhibition**. However, as a transcription factor lacking a conventional active site, it is considered "undruggable" by traditional small-molecule inhibitors. Current research focuses on indirect inhibition strategies, such as targeting upstream stabilizing kinases like Aurora A ([Link](https://doi.org/10.1073/pnas.1610626113)), inhibiting key downstream transcriptional targets, or developing proteolysis-targeting chimeras (PROTACs) to induce its degradation. These approaches hold promise for treating aggressive cancers driven by this potent oncogene.

Genular Protein ID: 343184804

Symbol: MYCN_HUMAN

Name: N-myc proto-oncogene protein

UniProtKB Accession Codes:

P04198 Q53XS5 Q6LDT9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 EMBL 14 Ensembl 1 ExpressionAtlas 1 GO 18 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 5 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 4 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 2 PIRSF 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 5 SIGNOR 1 SMART 1 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: 2869488

Title: Nucleotide sequence of the human N-myc gene.

PubMed ID: 2869488

DOI: 10.1073/pnas.83.6.1772

PubMed ID: 3510398

Title: Human N-myc is closely related in organization and nucleotide sequence to c-myc.

PubMed ID: 3510398

DOI: 10.1038/319073a0

PubMed ID: 2834684

Title: Sequence of a germ-line N-myc gene and amplification as a mechanism of activation.

PubMed ID: 2834684

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 3437890

Title: Alternative processing of RNA transcribed from NMYC.

PubMed ID: 3437890

DOI: 10.1128/mcb.7.12.4266-4272.1987

PubMed ID: 3008339

Title: Identification and characterization of the protein encoded by the human N-myc oncogene.

PubMed ID: 3008339

DOI: 10.1126/science.3008339

PubMed ID: 2987858

Title: Nucleotide sequence of the 3' exon of the human N-myc gene.

PubMed ID: 2987858

DOI: 10.1093/nar/13.7.2545

PubMed ID: 1425701

Title: Specific phosphorylation of the acidic central region of the N-myc protein by casein kinase II.

PubMed ID: 1425701

DOI: 10.1111/j.1432-1033.1992.tb17367.x

PubMed ID: 17311883

Title: The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth.

PubMed ID: 17311883

DOI: 10.1101/gad.1523007

PubMed ID: 18488021

Title: The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein.

PubMed ID: 18488021

DOI: 10.1038/ncb1727

PubMed ID: 24391509

Title: NCYM, a Cis-antisense gene of MYCN, encodes a de novo evolved protein that inhibits GSK3beta resulting in the stabilization of MYCN in human neuroblastomas.

PubMed ID: 24391509

DOI: 10.1371/journal.pgen.1003996

PubMed ID: 34342803

Title: The 9aaTAD Activation Domains in the Yamanaka Transcription Factors Oct4, Sox2, Myc, and Klf4.

PubMed ID: 34342803

DOI: 10.1007/s12015-021-10225-8

PubMed ID: 27837025

Title: Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors.

PubMed ID: 27837025

DOI: 10.1073/pnas.1610626113

PubMed ID: 15821734

Title: MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome.

PubMed ID: 15821734

DOI: 10.1038/ng1546

PubMed ID: 16906565

Title: Expanding the clinical spectrum of MYCN-related Feingold syndrome.

PubMed ID: 16906565

DOI: 10.1002/ajmg.a.31407

PubMed ID: 30573562

Title: MYCN de novo gain-of-function mutation in a patient with a novel megalencephaly syndrome.

PubMed ID: 30573562

DOI: 10.1136/jmedgenet-2018-105487

PubMed ID: 37710961

Title: Gain-of-function MYCN causes a megalencephaly-polydactyly syndrome manifesting mirror phenotypes of Feingold syndrome.

PubMed ID: 37710961

DOI: 10.1016/j.xhgg.2023.100238

Sequence Information:

  • Length: 464
  • Mass: 49561
  • Checksum: 560E885602E30DAD
  • Sequence:
    • MPSCSTSTMP GMICKNPDLE FDSLQPCFYP DEDDFYFGGP DSTPPGEDIW KKFELLPTPP 
LSPSRGFAEH SSEPPSWVTE MLLENELWGS PAEEDAFGLG GLGGLTPNPV ILQDCMWSGF 
SAREKLERAV SEKLQHGRGP PTAGSTAQSP GAGAASPAGR GHGGAAGAGR AGAALPAELA 
HPAAECVDPA VVFPFPVNKR EPAPVPAAPA SAPAAGPAVA SGAGIAAPAG APGVAPPRPG 
GRQTSGGDHK ALSTSGEDTL SDSDDEDDEE EDEEEEIDVV TVEKRRSSSN TKAVTTFTIT 
VRPKNAALGP GRAQSSELIL KRCLPIHQQH NYAAPSPYVE SEDAPPQKKI KSEASPRPLK 
SVIPPKAKSL SPRNSDSEDS ERRRNHNILE RQRRNDLRSS FLTLRDHVPE LVKNEKAAKV 
VILKKATEYV HSLQAEEHQL LLEKEKLQAR QQQLLKKIEH ARTC

Genular Protein ID: 4144315324

Symbol: A0A1W2PPD9_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A1W2PPD9

Database IDs:

ARBA 2 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 5 Gene3D 1 GeneTree 1 HGNC 1 InterPro 5 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 2 PeptideAtlas 2 Pfam 2 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 2 SMART 1 SMR 1 SUPFAM 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

Sequence Information:

  • Length: 253
  • Mass: 28360
  • Checksum: E3CCB8E31F8F0F06
  • Sequence:
    • MRGAPGNCVG AEQALARRKR AQTVAIRGHP RPPGPPGDTR AESPPDPLQS AGDDEDDEEE 
DEEEEIDVVT VEKRRSSSNT KAVTTFTITV RPKNAALGPG RAQSSELILK RCLPIHQQHN 
YAAPSPYVES EDAPPQKKIK SEASPRPLKS VIPPKAKSLS PRNSDSEDSE RRRNHNILER 
QRRNDLRSSF LTLRDHVPEL VKNEKAAKVV ILKKATEYVH SLQAEEHQLL LEKEKLQARQ 
QQLLKKIEHA RTC

Genular Protein ID: 2544588667

Symbol: Q9H224_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q9H224

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 NCBI Taxonomy 1 OrthoDB 1 RefSeq 1 SAM 1

Sequence Information:

  • Length: 112
  • Mass: 11765
  • Checksum: 215B85EC5C04BD63
  • Sequence:
    • MRGAPGNCVG AEQALARRKR AQTVAIRGHP RPPGPPGDTR AESPPDPLQS AGVLEVGAGP 
RLPRPPREGS TPGIKTNGAE RSPQSPAGRR ADAELLHVHH AGHDLQEPRP RV