Details for: MBNL3

Gene ID: 55796

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: MBNL3

Ensembl ID: ENSG00000076770

Description: muscleblind like splicing regulator 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • placental villous trophoblast CL2000060
    CSI 27.48
    rCSI 42.46%
    PRS 90.01
  • innate lymphoid cell CL0001065
    CSI 11.51
    rCSI 23.76%
    PRS 86.01
  • mucosal invariant T cell CL0000940
    CSI 11.28
    rCSI 9.11%
    PRS 95.7
  • erythroblast CL0000765
    CSI 8.01
    rCSI 21.25%
    PRS 92.23
  • Kupffer cell CL0000091
    CSI 6.29
    rCSI 14.39%
    PRS 92.6
  • extravillous trophoblast CL0008036
    CSI 5.97
    rCSI 7.38%
    PRS 90.24
  • hepatic stellate cell CL0000632
    CSI 5.73
    rCSI 21.47%
    PRS 87.85
  • mesothelial cell CL0000077
    CSI 5.42
    rCSI 21.19%
    PRS 76.54
  • mature B cell CL0000785
    CSI 5.1
    rCSI 4.44%
    PRS 96.44
  • erythrocyte CL0000232
    CSI 4.74
    rCSI 10.76%
    PRS 89.79
  • midzonal region hepatocyte CL0019028
    CSI 4.43
    rCSI 10.39%
    PRS 89.21
  • kidney connecting tubule epithelial cell CL1000768
    CSI 4.22
    rCSI 10.72%
    PRS 86.28
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.91
    rCSI 4.52%
    PRS 84.72
  • melanocyte CL0000148
    CSI 3.73
    rCSI 2.76%
    PRS 88.47
  • pro-B cell CL0000826
    CSI 3.7
    rCSI 3.07%
    PRS 92.75
  • vascular leptomeningeal cell CL4023051
    CSI 3.69
    rCSI 6.47%
    PRS 88.57
  • naive B cell CL0000788
    CSI 3.66
    rCSI 3.14%
    PRS 94.67
  • syncytiotrophoblast cell CL0000525
    CSI 3.38
    rCSI 9.75%
    PRS 92.82
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.35
    rCSI 3.02%
    PRS 90.48
  • parietal epithelial cell CL1000452
    CSI 2.92
    rCSI 7.81%
    PRS 86.97
  • hepatocyte CL0000182
    CSI 2.88
    rCSI 5.15%
    PRS 90.28
  • adipocyte CL0000136
    CSI 2.54
    rCSI 3.26%
    PRS 84.4
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.5
    rCSI 6.52%
    PRS 93.21
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.3
    rCSI 5.96%
    PRS 89.43
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.25
    rCSI 1.73%
    PRS 94.32
  • intestinal tuft cell CL0019032
    CSI 2.22
    rCSI 3.4%
    PRS 93.14
  • goblet cell CL0000160
    CSI 2.15
    rCSI 2.03%
    PRS 89.73
  • intrahepatic cholangiocyte CL0002538
    CSI 2.12
    rCSI 5.09%
    PRS 91.57
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.11
    rCSI 4.73%
    PRS 80.17
  • CD14-positive monocyte CL0001054
    CSI 2.03
    rCSI 2.53%
    PRS 96.32
  • lung secretory cell CL1000272
    CSI 2.01
    rCSI 4.99%
    PRS 92.41
  • BEST4+ enteroycte CL4030026
    CSI 1.97
    rCSI 2.45%
    PRS 91.36
  • renal beta-intercalated cell CL0002201
    CSI 1.9
    rCSI 4.52%
    PRS 91.79
  • small intestine goblet cell CL1000495
    CSI 1.8
    rCSI 3.95%
    PRS 93.61
  • centrilobular region hepatocyte CL0019029
    CSI 1.78
    rCSI 4.63%
    PRS 87.77
  • periportal region hepatocyte CL0019026
    CSI 1.77
    rCSI 6.88%
    PRS 88.65
  • cardiac muscle cell CL0000746
    CSI 1.68
    rCSI 2.42%
    PRS 84.36
  • renal principal cell CL0005009
    CSI 1.66
    rCSI 4.33%
    PRS 91.03
  • tuft cell of colon CL0009041
    CSI 1.62
    rCSI 3.76%
    PRS 93.05
  • neural progenitor cell CL0011020
    CSI 1.5
    rCSI 6.58%
    PRS 81.78
  • regular atrial cardiac myocyte CL0002129
    CSI 1.14
    rCSI 3.65%
    PRS 88.38
  • mesangial cell CL0000650
    CSI 1
    rCSI 4.09%
    PRS 95.61
  • podocyte CL0000653
    CSI 0.78
    rCSI 3.49%
    PRS 91.91
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.31
    rCSI 3.29%
    PRS 88.18

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.

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 [MBNL3](/details-gene/55796) (muscleblind like splicing regulator 3) is a protein-coding gene located on the X chromosome that functions primarily as an RNA-binding protein involved in the regulation of alternative splicing. Its expression profile indicates a highly specialized role, with overwhelmingly significant expression in [placental villous trophoblast](/details-cell/CL2000060), suggesting a critical function in placental development. The gene is also notably active in several immune and hematopoietic cell populations, including [innate lymphoid cells](/details-cell/CL0001065), [mucosal invariant T cells](/details-cell/CL0000940), and [erythroblasts](/details-cell/CL0000765). Functionally, [MBNL3](/details-gene/55796) is associated with processes such as [mRNA processing](/details-ontology/GO:0006397) and has been implicated in the [negative regulation of myoblast differentiation](/details-ontology/GO:0045662) [Link](https://doi.org/10.1006/dbio.2002.0798). The gene has a clinical association with myotonic dystrophy-like symptoms reported in OMIM ([300413](https://omim.org/entry/300413)). ## Cellular Roles and Expression Landscape The expression landscape of [MBNL3](/details-gene/55796) is characterized by highly specific and significant expression in a select number of cell types. **Overall**, the most prominent feature is its exceptionally high significance in [placental villous trophoblast](/details-cell/CL2000060) (CSI: 27.48), a score that is more than double that of the next highest cell type. This strongly suggests that [MBNL3](/details-gene/55796) is a key molecular player in the development, maintenance, or function of the placental barrier. Its notable expression in [extravillous trophoblast](/details-cell/CL0008036) further solidifies its importance in placental biology. Beyond its role in the placenta, [MBNL3](/details-gene/55796) demonstrates a significant role in the immune system and hematopoiesis. It is a significant marker for distinct lymphocyte populations, including [innate lymphoid cell](/details-cell/CL0001065) (CSI: 11.51) and [mucosal invariant T cell](/details-cell/CL0000940) (CSI: 11.28), as well as cells of the B-cell lineage such as [mature B cell](/details-cell/CL0000785) and [pro-B cell](/details-cell/CL0000826). Furthermore, its high significance in [erythroblast](/details-cell/CL0000765) (CSI: 8.01) and [erythrocyte](/details-cell/CL0000232) points towards a potential role in regulating gene expression during red blood cell development. The gene is also active in specialized tissue-resident cells like [Kupffer cells](/details-cell/CL0000091) and [hepatic stellate cells](/details-cell/CL0000632) in the liver. ## Pathways and Molecular Function [MBNL3](/details-gene/55796) is a member of the Muscleblind-like family of proteins, which are established regulators of alternative splicing [Link](https://doi.org/10.1038/sj.emboj.7600300). Consistent with this, its primary molecular function is [RNA binding](/details-ontology/GO:0003723), which it utilizes to control key biological processes. Gene Ontology annotations confirm its involvement in fundamental RNA-related activities, including [mRNA processing](/details-ontology/GO:0006397), [regulation of RNA splicing](/details-ontology/GO:0043484), and [RNA splicing](/details-ontology/GO:0008380) itself. These functions are consistent with its localization in both the [nucleoplasm](/details-ontology/GO:0005654) and [cytoplasm](/details-ontology/GO:0005737), allowing it to interact with RNA transcripts at various stages of their lifecycle. Notably, [MBNL3](/details-gene/55796) is also annotated for the [negative regulation of myoblast differentiation](/details-ontology/GO:0045662). Research has shown that it can act as an inhibitor of muscle differentiation, a function that contrasts with other members of its protein family [Link](https://doi.org/10.1006/dbio.2002.0798). This suggests that [MBNL3](/details-gene/55796) may regulate developmental programs by controlling the splicing of transcripts essential for cell fate decisions. ## Research Directions The highly specific expression pattern of [MBNL3](/details-gene/55796), particularly in placental tissue, alongside its known role as a splicing regulator, provides a foundation for several compelling research avenues. ### Testable Hypotheses 1. **Role in Placental Development:** Given its exceptionally high CSI score in [placental villous trophoblast](/details-cell/CL2000060), [MBNL3](/details-gene/55796) likely orchestrates a critical alternative splicing program required for proper trophoblast differentiation, fusion into the syncytiotrophoblast, and maintenance of the feto-maternal interface. Dysregulation or mutation of [MBNL3](/details-gene/55796) could therefore be a contributing factor to placental insufficiency or pre-eclampsia. 2. **Regulation of Hematopoiesis:** The high significance of [MBNL3](/details-gene/55796) in [erythroblasts](/details-cell/CL0000765) suggests it regulates key splicing events during erythropoiesis, such as the switch from fetal to adult hemoglobin or the processing of transcripts for crucial structural proteins. Its loss of function may lead to specific forms of anemia or red blood cell abnormalities. ### Key Experiments To test the hypothesis that [MBNL3](/details-gene/55796) is critical for placental function, a targeted molecular approach could be employed. Using a human trophoblast stem cell (TSC) model, one could perform a CRISPR-Cas9 knockout or shRNA-mediated knockdown of [MBNL3](/details-gene/55796). The impact on TSC self-renewal and differentiation into syncytiotrophoblasts and extravillous trophoblasts would be assessed using quantitative PCR for lineage markers (e.g., *CGB*, *HLA-G*), immunofluorescence, and cell fusion assays. Furthermore, performing RNA-sequencing on control versus knockdown cells would identify the direct splicing targets of [MBNL3](/details-gene/55796) and reveal the specific pathways it regulates in this vital tissue. ### Therapeutic Potential As an intracellular RNA-binding protein, [MBNL3](/details-gene/55796) presents a challenging direct target for conventional small-molecule inhibitors. However, if its dysregulation leads to pathogenic splicing events, it could be indirectly targeted. For example, if loss of [MBNL3](/details-gene/55796) function causes an aberrant splice isoform to be produced in a disease context, an antisense oligonucleotide (ASO) could be designed to correct this specific splicing defect. Given its highly restricted expression pattern, particularly in the placenta, such a therapeutic approach could potentially offer high specificity with minimal off-target effects in other adult tissues. It could also serve as a highly specific biomarker for placental health or certain hematopoietic disorders.

Genular Protein ID: 4133884905

Symbol: MBNL3_HUMAN

Name: Muscleblind-like protein 3

UniProtKB Accession Codes:

Q9NUK0 Q5JXN8 Q5JXN9 Q5JXP4 Q6UDQ1 Q8IUR4 Q8TAD9 Q8TAF4 Q9H0Z7 Q9UF37

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 16 Ensembl 7 ExpressionAtlas 1 GO 9 Gene3D 1 GeneCards 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 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 Pumba 1 RNAct 1 RefSeq 10 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12297108

Title: Inhibition of muscle differentiation by the novel muscleblind-related protein CHCR.

PubMed ID: 12297108

DOI: 10.1006/dbio.2002.0798

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 17974005

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

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 11929853

Title: Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells.

PubMed ID: 11929853

DOI: 10.1093/hmg/11.7.805

PubMed ID: 15257297

Title: Muscleblind proteins regulate alternative splicing.

PubMed ID: 15257297

DOI: 10.1038/sj.emboj.7600300

Sequence Information:

  • Length: 354
  • Mass: 38532
  • Checksum: 145E1AF8CB3BEE27
  • Sequence:
    • MTAVNVALIR DTKWLTLEVC REFQRGTCSR ADADCKFAHP PRVCHVENGR VVACFDSLKG 
RCTRENCKYL HPPPHLKTQL EINGRNNLIQ QKTAAAMFAQ QMQLMLQNAQ MSSLGSFPMT 
PSIPANPPMA FNPYIPHPGM GLVPAELVPN TPVLIPGNPP LAMPGAVGPK LMRSDKLEVC 
REFQRGNCTR GENDCRYAHP TDASMIEASD NTVTICMDYI KGRCSREKCK YFHPPAHLQA 
RLKAAHHQMN HSAASAMALQ PGTLQLIPKR SALEKPNGAT PVFNPTVFHC QQALTNLQLP 
QPAFIPAGPI LCMAPASNIV PMMHGATPTT VSAATTPATS VPFAAPTTGN QLKF