Details for: MESP2

Gene ID: 145873

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: MESP2

Ensembl ID: ENSG00000188095

Description: mesoderm posterior bHLH transcription factor 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • retinal cone cell CL0000573
    CSI 3.06
    rCSI 4.92%
    PRS 99.75
  • neural progenitor cell CL0011020
    CSI 2.94
    rCSI 12.95%
    PRS 98.74

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

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • 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 [MESP2](/details-gene/145873) (mesoderm posterior bHLH transcription factor 2) is a protein-coding gene located on chromosome 15q26.1. It encodes a basic helix-loop-helix (bHLH) transcription factor essential for embryonic development. Functionally, [MESP2](/details-gene/145873) is a master regulator of somitogenesis, particularly in the formation of the paraxial mesoderm and the specification of the rostral-caudal axis within somites. It operates within the nucleus, binding to DNA to control the transcription of target genes, and is critically involved in the [Notch signaling pathway](https://www.ebi.ac.uk/QuickGO/term/GO:0007219). Clinically, mutations in [MESP2](/details-gene/145873) are known to cause severe congenital vertebral malformations, including spondylocostal dysostosis and spondylothoracic dysostosis ([Link](https://doi.org/10.1086/421053); [Link](https://doi.org/10.1016/j.ajhg.2008.04.014)). While its role in mesodermal development is well-established, expression data also suggests a potential, less-characterized role in specific neural and retinal cell populations. ## Cellular Roles and Expression Landscape The expression profile of [MESP2](/details-gene/145873) underscores its highly specialized function, primarily during embryonic development. **Overall**, the provided data indicates its highest significance in cell types associated with development and differentiation. * **Top Associated Cells:** A significant expression association is observed in '[retinal cone cell](/details-cell/CL0000573)' (CSI: 3.06) and '[neural progenitor cell](/details-cell/CL0011020)' (CSI: 2.94). This suggests a potential role for [MESP2](/details-gene/145873) in the development or maintenance of these specific cell lineages, which extends beyond its canonical function in the mesoderm. The high significance in progenitors is consistent with a role in directing cell fate decisions during development. The presence of [MESP2](/details-gene/145873) in these ectoderm-derived lineages suggests a broader function in developmental patterning than previously understood, or the co-option of this key transcription factor in multiple, distinct developmental programs. ## Pathways and Molecular Function [MESP2](/details-gene/145873) functions as a sequence-specific DNA-binding transcription factor located in the [nucleus](https://www.ebi.ac.uk/QuickGO/term/GO:0005634), where it binds to [chromatin](https://www.ebi.ac.uk/QuickGO/term/GO:0000785) to regulate gene expression. Its molecular activity is central to key events in embryogenesis. * **Biological Processes:** The gene is integral to fundamental developmental processes including '[Developmental biology](https://reactome.org/content/detail/R-HSA-1266738)' and '[Gastrulation](https://reactome.org/content/detail/R-HSA-9758941)'. More specifically, it is a master regulator of '[Somitogenesis](https://reactome.org/content/detail/R-HSA-9824272)', governing '[Mesoderm formation](https://www.ebi.ac.uk/QuickGO/term/GO:0001707)' and '[Somite rostral/caudal axis specification](https://www.ebi.ac.uk/QuickGO/term/GO:0032525)'. Its involvement in the '[Notch signaling pathway](https://www.ebi.ac.uk/QuickGO/term/GO:0007219)' highlights its role in the segmentation clock that patterns the embryonic axis. * **Molecular Function:** As a transcription factor, its functions include '[Dna-binding transcription factor activity, rna polymerase ii-specific](https://www.ebi.ac.uk/QuickGO/term/GO:0000981)' and '[Protein dimerization activity](https://www.ebi.ac.uk/QuickGO/term/GO:0046983)', which is characteristic of bHLH proteins that often function as dimers to bind DNA effectively. The established roles in mesoderm formation provide a clear molecular basis for the skeletal abnormalities observed in patients with [MESP2](/details-gene/145873) mutations. ## Research Directions The functional profile of [MESP2](/details-gene/145873) as a crucial developmental regulator is well-supported, but the expression data suggests avenues for further research, particularly concerning its role outside of the mesoderm. The gene's established link to severe congenital disorders like spondylocostal dysostosis makes understanding its complete functional scope a clinical priority. **Proposed Hypotheses:** 1. Given its high significance score in '[retinal cone cell](/details-cell/CL0000573)', [MESP2](/details-gene/145873) may play a previously uncharacterized role in the specification or terminal differentiation of photoreceptor cells in the developing retina. 2. The high significance in '[neural progenitor cell](/details-cell/CL0011020)', coupled with its known interaction with Notch signaling, suggests that [MESP2](/details-gene/145873) may regulate the balance between self-renewal and differentiation in specific neural stem cell populations during central nervous system development. **Key Experimental Approach:** To test the hypothesis of [MESP2](/details-gene/145873)'s role in retinal development, a compelling experiment would be to use CRISPR-Cas9 to knock out the gene in human induced pluripotent stem cells (iPSCs). These iPSCs would then be differentiated into three-dimensional retinal organoids. The impact of the knockout could be assessed by comparing the cellular composition and structure of knockout versus wild-type organoids, specifically quantifying the population of cone photoreceptors using immunofluorescence for markers like OPN1SW and ARR3. Single-cell RNA-sequencing at different time points during organoid development would further reveal the transcriptomic consequences of [MESP2](/details-gene/145873) loss and identify its downstream targets in the retinal lineage. **Therapeutic Potential:** As a master developmental transcription factor, direct therapeutic targeting of [MESP2](/details-gene/145873) is challenging. Its primary clinical relevance is in the realm of genetic diagnostics for congenital skeletal disorders. However, if a role in retinal cell maintenance or regeneration were to be established, it could theoretically become a target for gene replacement therapies aimed at treating specific forms of retinal dystrophy. Currently, there is no indication for therapeutic inhibition or activation in postnatal contexts.

Genular Protein ID: 776485596

Symbol: MESP2_HUMAN

Name: Mesoderm posterior protein 2

UniProtKB Accession Codes:

Q0VG99 Q7RTU2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 11 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 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 14516699

Title: Exhaustive identification of human class II basic helix-loop-helix proteins by virtual library screening.

PubMed ID: 14516699

DOI: 10.1016/s0925-4773(03)00130-8

PubMed ID: 15122512

Title: Mutated MESP2 causes spondylocostal dysostosis in humans.

PubMed ID: 15122512

DOI: 10.1086/421053

PubMed ID: 18485326

Title: Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome.

PubMed ID: 18485326

DOI: 10.1016/j.ajhg.2008.04.014

Sequence Information:

  • Length: 397
  • Mass: 41760
  • Checksum: 6CC8A423D23BF88B
  • Sequence:
    • MAQSPPPQSL LGHDHWIFAQ GWGWAGHWDS TSPASSSDSS GSCPCDGARG LPQPQPPSCS 
SRAAEAAATT PRRARTGPAG GQRQSASERE KLRMRTLARA LHELRRFLPP SLAPAGQSLT 
KIETLRLAIR YIGHLSAVLG LSEESLQCRR RQRGDAGSPW GCPLCPDRGP AEAQTQAEGQ 
GQGQGQGQGQ GQGQGQGQGQ GQGQGRRPGL VSAVLAEASW GSPSACPGAQ AAPERLGRGV 
HDTDPWATPP YCPKIQSPPY SSQGTTSDAS LWTPPQGCPW TQSSPEPRNP PVPWTAAPAT 
LELAAVYQGL SVSPEPCLSL GAPSLLPHPS CQRLQPQTPG RCWSHSAEVV PNSEDQGPGA 
AFQLSEASPP QSSGLRFSGC PELWQEDLEG ARLGIFY