Details for: MFSD2B

Gene ID: 388931

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: MFSD2B

Ensembl ID: ENSG00000205639

Description: MFSD2 lysolipid transporter B, sphingolipid

Cell Significance Landscape

Associated with

Significant Cells

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

  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 4.57
    rCSI 4.13%
    PRS 99.55
  • erythrocyte CL0000232
    CSI 4.11
    rCSI 9.32%
    PRS 99.09
  • platelet CL0000233
    CSI 1.97
    rCSI 8.18%
    PRS 97.86
  • erythroblast CL0000765
    CSI 1.65
    rCSI 4.37%
    PRS 99.45
  • primitive red blood cell CL0002355
    CSI 1.15
    rCSI 6.22%
    PRS 99.43
  • megakaryocyte CL0000556
    CSI 1.14
    rCSI 4.94%
    PRS 98.77
  • erythroid progenitor cell CL0000038
    CSI 0.6
    rCSI 3.41%
    PRS 99.53

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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  • 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 [MFSD2B](/details-gene/388931) (Major Facilitator Superfamily Domain Containing 2B) is a protein-coding gene located on chromosome 2. It functions as a crucial transmembrane transporter, specializing in the export of the signaling lipid sphingosine-1-phosphate (S1P) ([Link](https://doi.org/10.1038/nature24053), [Link](https://doi.org/10.1038/s41598-018-23300-x)). Expression data indicates that [MFSD2B](/details-gene/388931) is a highly specific and significant gene within the hematopoietic system, particularly in cells of the erythroid and megakaryocytic lineages, such as [erythrocytes](/details-cell/CL0000232) and [platelets](/details-cell/CL0000233). Its primary role is to maintain S1P homeostasis in the blood, which is essential for normal platelet function and erythrocyte biology. ## Cellular Roles and Expression Landscape The expression profile of [MFSD2B](/details-gene/388931) firmly establishes its identity as a key gene in hematopoiesis, with a specialized role in the development and function of red blood cells and platelets. **Overall**, the gene shows its highest significance in cell types dedicated to oxygen transport and hemostasis. It is most prominent in [megakaryocyte-erythroid progenitor cells](/details-cell/CL0000050) (CSI: 4.57), mature [erythrocytes](/details-cell/CL0000232) (CSI: 4.11), and [platelets](/details-cell/CL0000233) (CSI: 1.97). High significance is also observed in precursor cells like [erythroblasts](/details-cell/CL0000765) and [megakaryocytes](/details-cell/CL0000556). This pattern suggests that [MFSD2B](/details-gene/388931) is not only a marker of these mature cell types but also plays a continuous and vital role throughout their differentiation from common progenitors. The strong and specific expression signature within this narrow lineage highlights its specialized function, which is distinct from other hematopoietic or somatic cell types. ## Pathways and Molecular Function The molecular function of [MFSD2B](/details-gene/388931) is directly aligned with its cellular expression pattern. As a member of the major facilitator superfamily, it exhibits 'Sphingolipid transporter activity' ([GO:0046624](https://www.ebi.ac.uk/QuickGO/term/GO:0046624)) and is a key component of the 'Plasma membrane' ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)). Its primary function is the transport of sphingolipids, a process central to 'Sphingolipid metabolism' ([R-HSA-428157](https://reactome.org/content/detail/R-HSA-428157)). Research has confirmed that [MFSD2B](/details-gene/388931) is the essential exporter of sphingosine-1-phosphate (S1P) from both [erythrocytes](/details-cell/CL0000232) and [platelets](/details-cell/CL0000233) ([Link](https://doi.org/10.1038/nature24053)). This function is critical, as S1P in the plasma is a potent signaling molecule that regulates vascular integrity, immune cell trafficking, and thrombosis. Consistent with this, [MFSD2B](/details-gene/388931) is implicated in the 'Positive regulation of platelet aggregation' ([GO:1901731](https://www.ebi.ac.uk/QuickGO/term/GO:1901731)) and the 'Sphingosine-1-phosphate receptor signaling pathway' ([GO:0003376](https://www.ebi.ac.uk/QuickGO/term/GO:0003376)). By controlling the efflux of S1P from the most abundant cells in the blood, [MFSD2B](/details-gene/388931) is a master regulator of circulating S1P levels. ## Research Directions The highly specific role of [MFSD2B](/details-gene/388931) in controlling plasma S1P levels via its activity in [erythrocytes](/details-cell/CL0000232) and [platelets](/details-cell/CL0000233) opens several avenues for future research into hematological and vascular diseases. **Proposed Hypotheses:** 1. Genetic variants or loss-of-function mutations in [MFSD2B](/details-gene/388931) may be an underlying cause of certain bleeding disorders or thrombocythemias. A failure to properly export S1P from [platelets](/details-cell/CL0000233) could impair their aggregation response, while defects in S1P transport from [erythrocytes](/details-cell/CL0000232) could lead to abnormal cell morphology and reduced lifespan, potentially causing a form of anemia. 2. In pathological states such as sepsis or acute coronary syndrome, where vascular leakage and thrombosis are central features, the expression or activity of [MFSD2B](/details-gene/388931) may be dynamically regulated. Altered [MFSD2B](/details-gene/388931) function in these conditions could significantly disrupt plasma S1P gradients, thereby contributing to disease progression. **Experimental Approach:** To test the first hypothesis regarding the role of [MFSD2B](/details-gene/388931) in hemostasis and erythrocyte stability, a hematopoietic-specific conditional knockout mouse model would be highly informative. By deleting *Mfsd2b* using a Vav1-Cre or similar system, one could specifically assess its function in blood cells. Key experimental readouts would include: * Complete blood counts to assess for anemia, thrombocytopenia, or other cytopenias. * *Ex vivo* platelet aggregometry using various agonists (e.g., ADP, collagen) to measure functional defects in hemostasis. * Measurement of plasma S1P levels via mass spectrometry to confirm the disruption of S1P export. * Analysis of erythrocyte fragility and lifespan using osmotic fragility tests and *in vivo* biotinylation assays. **Therapeutic Potential:** Given its highly specific expression in the erythroid/megakaryocytic lineage and its role as a transporter on the cell surface, [MFSD2B](/details-gene/388931) presents a compelling, albeit specialized, therapeutic target. In prothrombotic conditions characterized by excessive platelet activation, a selective small-molecule inhibitor of [MFSD2B](/details-gene/388931) could offer a novel anti-platelet strategy. By blocking S1P export specifically from [platelets](/details-cell/CL0000233) and [erythrocytes](/details-cell/CL0000232), such an inhibitor could locally dampen prothrombotic signaling at sites of vascular injury without the systemic side effects associated with targeting S1P receptors, which are expressed ubiquitously. Therefore, inhibition of [MFSD2B](/details-gene/388931) is the most likely therapeutic approach.

Genular Protein ID: 3332570834

Symbol: MFS2B_HUMAN

Name: N/A

UniProtKB Accession Codes:

A6NFX1 B5MC32 J3KNU6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 3 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 8 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 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 Reactome 1 RefSeq 1 Rhea 3 SMR 1 STRING 1 SUPFAM 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

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: 18694395

Title: Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis.

PubMed ID: 18694395

DOI: 10.1042/bj20080165

PubMed ID: 29045386

Title: Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes and platelets.

PubMed ID: 29045386

DOI: 10.1038/nature24053

PubMed ID: 29563527

Title: MFSD2B is a sphingosine 1-phosphate transporter in erythroid cells.

PubMed ID: 29563527

DOI: 10.1038/s41598-018-23300-x

Sequence Information:

  • Length: 504
  • Mass: 53743
  • Checksum: 22812066AECE07B8
  • Sequence:
    • MAAPPAPAAK GSPQPEPHAP EPGPGSAKRG REDSRAGRLS FCTKVCYGIG GVPNQIASSA 
TAFYLQLFLL DIAQIPAAQV SLVLFGGKVS GAAADPVAGF FINRSQRTGS GRLMPWVLGC 
TPFIALAYFF LWFLPPFTSL RGLWYTTFYC LFQALATFFQ VPYTALTMLL TPCPRERDSA 
TAYRMTVEMA GTLMGATVHG LIVSGAHRPH RCEATATPGP VTVSPNAAHL YCIAAAVVVV 
TYPVCISLLC LGVKERPDPS APASGPGLSF LAGLSLTTRH PPYLKLVISF LFISAAVQVE 
QSYLVLFCTH ASQLHDHVQG LVLTVLVSAV LSTPLWEWVL QRFGKKTSAF GIFAMVPFAI 
LLAAVPTAPV AYVVAFVSGV SIAVSLLLPW SMLPDVVDDF QLQHRHGPGL ETIFYSSYVF 
FTKLSGACAL GISTLSLEFS GYKAGVCKQA EEVVVTLKVL IGAVPTCMIL AGLCILMVGS 
TPKTPSRDAS SRLSLRRRTS YSLA