Details for: MAB21L2

Gene ID: 10586

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: MAB21L2

Ensembl ID: ENSG00000181541

Description: mab-21 like 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • enteric smooth muscle cell CL0002504
    CSI 27.14
    rCSI 38.73%
    PRS 97.58
  • mesodermal cell CL0000222
    CSI 26.11
    rCSI 31.34%
    PRS 97.47
  • interstitial cell of Cajal CL0002088
    CSI 16.07
    rCSI 20.46%
    PRS 98.54
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 12.87
    rCSI 16.52%
    PRS 95.27
  • myofibroblast cell CL0000186
    CSI 11.19
    rCSI 15.5%
    PRS 95.61
  • retina horizontal cell CL0000745
    CSI 6.25
    rCSI 9.53%
    PRS 95.4
  • stromal cell CL0000499
    CSI 6.19
    rCSI 17.42%
    PRS 95.61
  • chondrocyte CL0000138
    CSI 4.58
    rCSI 7.28%
    PRS 94.89
  • cytotoxic T cell CL0000910
    CSI 3.97
    rCSI 22.76%
    PRS 94.19
  • mesenchymal cell CL0008019
    CSI 3.93
    rCSI 9.97%
    PRS 95.69
  • radial glial cell CL0000681
    CSI 3.77
    rCSI 5.23%
    PRS 96.67
  • helper T cell CL0000912
    CSI 3.55
    rCSI 5.02%
    PRS 92.62
  • innate lymphoid cell CL0001065
    CSI 3.37
    rCSI 6.96%
    PRS 91.99
  • basal cell of epidermis CL0002187
    CSI 3.31
    rCSI 5.87%
    PRS 77.07
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 2.23
    rCSI 2.7%
    PRS 83.01
  • smooth muscle cell CL0000192
    CSI 1.98
    rCSI 4.72%
    PRS 94.67
  • melanocyte of skin CL1000458
    CSI 1.52
    rCSI 2.07%
    PRS 77.9
  • suprabasal keratinocyte CL4033013
    CSI 0.98
    rCSI 1.59%
    PRS 78.17

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)

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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 [MAB21L2](/details-gene/10586) (mab-21 like 2) is a protein-coding gene located on chromosome 4q31.3. It is a human homolog of the *C. elegans* cell fate determination gene *mab-21* [[Link](https://pubmed.ncbi.nlm.nih.gov/10556287/)]. Functionally, [MAB21L2](/details-gene/10586) is critically involved in embryonic development, particularly in the formation of the eye and nervous system. Consistent with this, mutations in the gene are known to cause a range of major eye malformations, including ocular coloboma, microcornea, and cataracts [[Link](https://doi.org/10.1016/j.ajhg.2014.05.005), [Link](https://doi.org/10.1371/journal.pgen.1005002)]. Expression data from an **Overall** context reveals its highest significance in cell types of mesenchymal and neural origin, such as [enteric smooth muscle cell](/details-cell/CL0002504), [mesodermal cell](/details-cell/CL0000222), and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031), underscoring its fundamental role in morphogenesis and cell differentiation. ## Cellular Roles and Expression Landscape The expression profile of [MAB21L2](/details-gene/10586) highlights its specialized role in developmental and mesenchymal cell lineages. **Overall**, the gene shows the highest significance in [enteric smooth muscle cell](/details-cell/CL0002504) (CSI: 27.14) and [mesodermal cell](/details-cell/CL0000222) (CSI: 26.11), suggesting a primary function in the development and maintenance of mesoderm-derived tissues, particularly within the gastrointestinal system. Its high significance in [interstitial cell of Cajal](/details-cell/CL0002088) and [myofibroblast cell](/details-cell/CL0000186) further reinforces its importance in gut motility and stromal architecture. A secondary but crucial role in neural and ocular development is also evident. [MAB21L2](/details-gene/10586) is a significant marker in [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) and [retina horizontal cell](/details-cell/CL0000745), which aligns directly with its established clinical link to eye malformations. The gene's activity in other developmental cell types, including [chondrocyte](/details-cell/CL0000138) and [stromal cell](/details-cell/CL0000499), points towards a broader function in organogenesis and tissue scaffolding. While also expressed in some mature immune populations like [cytotoxic T cell](/details-cell/CL0000910) and [helper T cell](/details-cell/CL0000912), its significance is considerably lower, suggesting its primary impact is outside the hematopoietic system. ## Pathways and Molecular Function The functional annotations for [MAB21L2](/details-gene/10586) are highly consistent with its expression pattern and clinical relevance. It is a key participant in fundamental developmental processes, most notably '[Camera-type eye development](/details-go/GO:0043010)' and '[Nervous system development](/details-go/GO:0007399)'. Its involvement in broader morphogenetic events is captured by annotations for '[Embryonic body morphogenesis](/details-go/GO:0010172)'. At the cellular level, [MAB21L2](/details-gene/10586) is associated with '[Cell population proliferation](/details-go/GO:0008283)' and its positive regulation, a critical function for tissue growth during development. The protein product is known to be localized to both the '[Cytoplasm](/details-go/GO:0005737)' and the '[Nucleus](/details-go/GO:0005634)' and possesses '[Protein binding](/details-go/GO:0005515)' capabilities. This suggests it may function as an adaptor or scaffold protein, potentially as part of a larger complex that regulates gene expression or signaling pathways essential for cell fate decisions during embryogenesis. ## Research Directions The established role of [MAB21L2](/details-gene/10586) in eye development is well-documented, but its high significance in cell types of the enteric system presents a compelling avenue for new research. Based on the available data, several testable hypotheses can be proposed: 1. Given its high significance in [enteric smooth muscle cell](/details-cell/CL0002504) and [interstitial cell of Cajal](/details-cell/CL0002088), dysregulation or mutation of [MAB21L2](/details-gene/10586) may contribute to congenital gastrointestinal motility disorders, such as Hirschsprung's disease or chronic intestinal pseudo-obstruction, by impairing the development or function of the enteric neuromuscular system. 2. The gene's strong expression in multiple mesenchymal lineages ([mesodermal cell](/details-cell/CL0000222), [myofibroblast cell](/details-cell/CL0000186), [chondrocyte](/details-cell/CL0000138)) suggests that [MAB21L2](/details-gene/10586) functions as a pleiotropic regulator of mesenchymal cell fate, and that subclinical phenotypes related to connective tissue or organ structure may be present in individuals with known MAB21L2-related oculopathies. **Experimental Proposal:** To test the first hypothesis regarding its role in enteric function, a mouse model with a conditional knockout of *Mab21l2* in either smooth muscle precursors (e.g., using a *Sm22a-Cre* driver) or neural crest derivatives (e.g., using a *Wnt1-Cre* driver) could be generated. The resulting phenotypes could be assessed through a combination of *in vivo* gastrointestinal transit assays, *ex vivo* muscle strip contractility studies, and detailed immunohistochemical analysis of the enteric nervous system and smooth muscle layers in the developing and adult gut. **Therapeutic Potential:** As [MAB21L2](/details-gene/10586) is a critical developmental gene whose loss-of-function leads to severe malformations, it is not a suitable target for therapeutic inhibition. Its primary clinical utility lies in genetic diagnostics for patients with congenital eye and potentially other developmental anomalies. In the long term, therapeutic strategies would be highly speculative and likely confined to the realm of gene replacement therapy for early embryonic conditions, which faces immense technical and ethical challenges. Therefore, its immediate value is in diagnostics and in furthering our understanding of fundamental developmental biology.

Genular Protein ID: 932575970

Symbol: MB212_HUMAN

Name: Protein mab-21-like 2

UniProtKB Accession Codes:

Q9Y586 B3KP37 Q9HBA7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 GO 8 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10556287

Title: Two murine and human homologs of mab-21, a cell fate determination gene involved in Caenorhabditis elegans neural development.

PubMed ID: 10556287

DOI: 10.1093/hmg/8.13.2397

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 24906020

Title: Monoallelic and biallelic mutations in MAB21L2 cause a spectrum of major eye malformations.

PubMed ID: 24906020

DOI: 10.1016/j.ajhg.2014.05.005

PubMed ID: 25719200

Title: Mutations in MAB21L2 result in ocular Coloboma, microcornea and cataracts.

PubMed ID: 25719200

DOI: 10.1371/journal.pgen.1005002

Sequence Information:

  • Length: 359
  • Mass: 40923
  • Checksum: 24AFD8AF1600C1AA
  • Sequence:
    • MIAAQAKLVY QLNKYYTERC QARKAAIAKT IREVCKVVSD VLKEVEVQEP RFISSLSEID 
ARYEGLEVIS PTEFEVVLYL NQMGVFNFVD DGSLPGCAVL KLSDGRKRSM SLWVEFITAS 
GYLSARKIRS RFQTLVAQAV DKCSYRDVVK MIADTSEVKL RIRERYVVQI TPAFKCTGIW 
PRSAAQWPMP HIPWPGPNRV AEVKAEGFNL LSKECYSLTG KQSSAESDAW VLQFGEAENR 
LLMGGCRNKC LSVLKTLRDR HLELPGQPLN NYHMKTLLLY ECEKHPRETD WDESCLGDRL 
NGILLQLISC LQCRRCPHYF LPNLDLFQGK PHSALESAAK QTWRLAREIL TNPKSLDKL