Details for: WNT2B

Gene ID: 7482

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: WNT2B

Ensembl ID: ENSG00000134245

Description: Wnt family member 2B

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • myofibroblast cell CL0000186
    CSI 7.02
    rCSI 9.73%
    PRS 79.72
  • parietal epithelial cell CL1000452
    CSI 6.11
    rCSI 16.33%
    PRS 75.17
  • alveolar macrophage CL0000583
    CSI 5.01
    rCSI 8.26%
    PRS 86.31
  • conjunctival epithelial cell CL1000432
    CSI 4.52
    rCSI 6.9%
    PRS 82.81
  • stromal cell CL0000499
    CSI 3.56
    rCSI 10.02%
    PRS 77.89
  • retinal blood vessel endothelial cell CL0002585
    CSI 3.12
    rCSI 4.98%
    PRS 86.16
  • Kupffer cell CL0000091
    CSI 3.02
    rCSI 6.9%
    PRS 83.59
  • hepatic stellate cell CL0000632
    CSI 2.99
    rCSI 11.19%
    PRS 75.75
  • mesodermal cell CL0000222
    CSI 2.74
    rCSI 3.29%
    PRS 80.95
  • interneuron CL0000099
    CSI 2.73
    rCSI 5.48%
    PRS 73.9
  • blood vessel endothelial cell CL0000071
    CSI 2.57
    rCSI 5.34%
    PRS 79.79
  • mature microglial cell CL0002629
    CSI 2.55
    rCSI 10.61%
    PRS 82.87
  • choroid plexus epithelial cell CL0000706
    CSI 2.26
    rCSI 3.7%
    PRS 72.85
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.03
    rCSI 5.3%
    PRS 83.82
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.97
    rCSI 2.36%
    PRS 65.73
  • respiratory suprabasal cell CL4033048
    CSI 1.95
    rCSI 2.5%
    PRS 85.6
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.94
    rCSI 3.26%
    PRS 65.66
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.91
    rCSI 2.46%
    PRS 66.81
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.9
    rCSI 2.37%
    PRS 63.55
  • Mueller cell CL0000636
    CSI 1.88
    rCSI 4.29%
    PRS 74.64
  • adventitial cell CL0002503
    CSI 1.87
    rCSI 4.48%
    PRS 86.26
  • cerebral cortex endothelial cell CL1001602
    CSI 1.83
    rCSI 3.16%
    PRS 74.96
  • cardiac endothelial cell CL0010008
    CSI 1.78
    rCSI 7.18%
    PRS 82.89
  • pulmonary artery endothelial cell CL1001568
    CSI 1.72
    rCSI 2.35%
    PRS 90.23
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 1.59
    rCSI 4.89%
    PRS 86.48
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.56
    rCSI 1.89%
    PRS 89.49
  • corneal epithelial cell CL0000575
    CSI 1.52
    rCSI 4.34%
    PRS 87.81
  • epithelial cell of proximal tubule CL0002306
    CSI 1.52
    rCSI 3.71%
    PRS 75.23
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.39
    rCSI 2.46%
    PRS 65.2
  • basal cell of epidermis CL0002187
    CSI 1.37
    rCSI 2.43%
    PRS 51.98
  • retinal cone cell CL0000573
    CSI 1.36
    rCSI 2.18%
    PRS 73.37
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.35
    rCSI 2.17%
    PRS 67.01
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.26
    rCSI 3.25%
    PRS 78.51
  • tissue-resident macrophage CL0000864
    CSI 1.22
    rCSI 5.69%
    PRS 92.46
  • cardiac neuron CL0010022
    CSI 1.08
    rCSI 3.44%
    PRS 80.46
  • endothelial cell of placenta CL0009092
    CSI 1.05
    rCSI 5.17%
    PRS 89.38
  • melanocyte of skin CL1000458
    CSI 1.01
    rCSI 1.37%
    PRS 50.26
  • mesenchymal cell CL0008019
    CSI 0.93
    rCSI 2.36%
    PRS 76.59
  • enteroglial cell CL4040002
    CSI 0.92
    rCSI 4.83%
    PRS 83.72
  • pulmonary alveolar type 1 cell CL0002062
    CSI 0.88
    rCSI 5.09%
    PRS 79.19
  • retinal ganglion cell CL0000740
    CSI 0.83
    rCSI 1.83%
    PRS 69.28
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.82
    rCSI 2%
    PRS 63.61
  • stromal cell of ovary CL0002132
    CSI 0.69
    rCSI 1.89%
    PRS 88.65
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.64
    rCSI 1.99%
    PRS 67.33
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.59
    rCSI 1.83%
    PRS 69.61
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.49
    rCSI 1.78%
    PRS 63.58
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.27
    rCSI 6.57%
    PRS 64.24

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):
    • 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 [WNT2B](/details-gene/7482) is a protein-coding gene that encodes Wnt-2b, a secreted signaling protein belonging to the Wnt family. As a key ligand, it participates in the [canonical Wnt signaling pathway](/details-go/GO0060070), a critical cascade for embryonic development, [cell fate commitment](/details-go/GO0045165), and tissue homeostasis. Its molecular function involves binding to Frizzled family receptors ([GO:0005109](/details-go/GO0005109)), thereby initiating intracellular signaling. **Overall**, expression data reveals its highest significance in mesenchymal cell types such as [myofibroblast cell](/details-cell/CL0000186) and [stromal cell](/details-cell/CL0000499), as well as in various tissue-resident macrophage populations and specialized epithelial cells. Clinically, homozygous loss-of-function mutations in [WNT2B](/details-gene/7482) are associated with neonatal-onset chronic diarrhea ([Link](https://doi.org/10.1016/j.ajhg.2018.05.007)), highlighting its essential role in intestinal development and function ([153245](https://omim.org/entry/601968)). ## Cellular Roles and Expression Landscape The expression profile of [WNT2B](/details-gene/7482) suggests a fundamental role in intercellular communication, tissue architecture, and localized immune modulation rather than serving as a lineage marker for a single cell type. - **Mesenchymal and Stromal Cells:** The gene shows the highest significance in [myofibroblast cell](/details-cell/CL0000186) (CSI: 7.02), [stromal cell](/details-cell/CL0000499), and [hepatic stellate cell](/details-cell/CL0000632). These cells are critical for synthesizing extracellular matrix and orchestrating tissue repair and remodeling. This expression pattern is consistent with the known functions of Wnt signaling in fibrosis and tissue regeneration. - **Tissue-Resident Macrophages:** [WNT2B](/details-gene/7482) is also a significant marker in several tissue-resident macrophage populations, including [alveolar macrophage](/details-cell/CL0000583) (CSI: 5.01) in the lung, [Kupffer cell](/details-cell/CL0000091) in the liver, and [mature microglial cell](/details-cell/CL0002629) in the central nervous system. This suggests a potential role for [WNT2B](/details-gene/7482) in modulating the local immune environment and contributing to the homeostatic and tissue-repair functions of these specialized phagocytes. - **Specialized Epithelial and Endothelial Cells:** High significance is also noted in specific epithelial and endothelial contexts, such as [parietal epithelial cell](/details-cell/CL1000452) of the kidney, [conjunctival epithelial cell](/details-cell/CL1000432) of the eye, and [retinal blood vessel endothelial cell](/details-cell/CL0002585). This aligns with its annotated roles in cornea, lens, and ureteric bud morphogenesis, pointing to its involvement in organ-specific developmental programs. ## Pathways and Molecular Function [WNT2B](/details-gene/7482) functions as an extracellular ligand, consistent with its annotation as having [cytokine activity](/details-go/GO0005125) and localizing to the [extracellular space](/details-go/GO0005615). Its primary mechanism of action is through the [Signaling by Wnt](/details-pathway/R-HSA-195721) pathway, a core component of metazoan [signal transduction](/details-pathway/R-HSA-162582). As a lipidated protein, its solubility and activity in the extracellular environment are maintained by carrier proteins like afamin ([Link](https://doi.org/10.7554/elife.11621)). By binding to Frizzled receptors on target cells, [WNT2B](/details-gene/7482) activates downstream signaling that regulates gene expression. This activation underpins its involvement in a wide array of developmental processes, including [hematopoietic stem cell proliferation](/details-go/GO0071425), [neuron differentiation](/details-go/GO0030182), and [chondrocyte differentiation](/details-go/GO0002062). The gene's role in [mesenchymal-epithelial cell signaling](/details-go/GO0060638) provides a direct molecular explanation for its expression in both stromal and epithelial cell compartments and its importance in organogenesis. ## Research Directions The diverse expression pattern of [WNT2B](/details-gene/7482) across mesenchymal, immune, and epithelial cells, combined with its fundamental role in Wnt signaling, opens several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high significance in [myofibroblast cell](/details-cell/CL0000186) and [hepatic stellate cell](/details-cell/CL0000632), [WNT2B](/details-gene/7482) may be a key paracrine factor that drives pathological fibrosis in organs like the lung, liver, and kidney. Its inhibition could represent a novel anti-fibrotic strategy. 2. The prominent expression in tissue-resident macrophages ([alveolar macrophage](/details-cell/CL0000583), [Kupffer cell](/details-cell/CL0000091)) suggests that [WNT2B](/details-gene/7482) signaling, either in an autocrine or paracrine fashion, is critical for maintaining the tissue-repair and anti-inflammatory (M2-like) phenotype of these cells. 3. Based on its clinical association with neonatal diarrhea ([Link](https://doi.org/10.1016/j.ajhg.2018.05.007)), [WNT2B](/details-gene/7482) produced by intestinal myofibroblasts likely acts as a critical niche factor for maintaining the intestinal stem cell pool and promoting epithelial renewal. **Suggested Experimental Approach:** To test the hypothesis that [WNT2B](/details-gene/7482) modulates macrophage phenotype (Hypothesis 2), one could perform *in vitro* polarization assays. Primary human monocytes could be differentiated into macrophages and then treated with recombinant WNT2B protein or have [WNT2B](/details-gene/7482) expression silenced using siRNA. The impact on macrophage polarization could be assessed by measuring the expression of M1 (e.g., TNF, IL6) and M2 (e.g., CD206, ARG1) markers via qRT-PCR and flow cytometry, as well as by functional assays such as phagocytosis and cytokine secretion profiling. **Therapeutic Potential:** As a secreted protein, Wnt-2b is an accessible therapeutic target. For diseases characterized by excessive fibrosis or Wnt-driven cancers, developing monoclonal antibodies or small molecule inhibitors that block the interaction of Wnt-2b with its Frizzled receptors would be a strategy of **inhibition**. Conversely, for conditions involving tissue damage or congenital deficiencies, a protein replacement therapy using a stabilized, recombinant form of Wnt-2b could be explored as a strategy of **activation** to promote regeneration and restore normal tissue function.

Genular Protein ID: 1186558414

Symbol: WNT2B_HUMAN

Name: Protein Wnt-2b

UniProtKB Accession Codes:

Q93097 O14903 Q5TEH9 Q5TEI2 Q9HDC1 Q9HDC2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 2 ExpressionAtlas 1 GO 20 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 2 RefSeq 3 SIGNOR 1 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 8761309

Title: Cloning, expression and chromosomal localization of Wnt-13, a novel member of the Wnt gene family.

PubMed ID: 8761309

PubMed ID: 10944466

Title: Alternative splicing of the WNT-2B/WNT-13 gene.

PubMed ID: 10944466

DOI: 10.1006/bbrc.2000.3252

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 9441749

Title: Isolation of two novel WNT genes, WNT14 and WNT15, one of which (WNT15) is closely linked to WNT3 on human chromosome 17q21.

PubMed ID: 9441749

DOI: 10.1006/geno.1997.5041

PubMed ID: 18780401

Title: Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry.

PubMed ID: 18780401

DOI: 10.1002/pmic.200701057

PubMed ID: 26902720

Title: Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/alpha-albumin.

PubMed ID: 26902720

DOI: 10.7554/elife.11621

PubMed ID: 29909964

Title: Neonatal-Onset Chronic Diarrhea Caused by Homozygous Nonsense WNT2B Mutations.

PubMed ID: 29909964

DOI: 10.1016/j.ajhg.2018.05.007

Sequence Information:

  • Length: 391
  • Mass: 43770
  • Checksum: BD7BB7F795FB33B1
  • Sequence:
    • MLRPGGAEEA AQLPLRRASA PVPVPSPAAP DGSRASARLG LACLLLLLLL TLPARVDTSW 
WYIGALGARV ICDNIPGLVS RQRQLCQRYP DIMRSVGEGA REWIRECQHQ FRHHRWNCTT 
LDRDHTVFGR VMLRSSREAA FVYAISSAGV VHAITRACSQ GELSVCSCDP YTRGRHHDQR 
GDFDWGGCSD NIHYGVRFAK AFVDAKEKRL KDARALMNLH NNRCGRTAVR RFLKLECKCH 
GVSGSCTLRT CWRALSDFRR TGDYLRRRYD GAVQVMATQD GANFTAARQG YRRATRTDLV 
YFDNSPDYCV LDKAAGSLGT AGRVCSKTSK GTDGCEIMCC GRGYDTTRVT RVTQCECKFH 
WCCAVRCKEC RNTVDVHTCK APKKAEWLDQ T

Genular Protein ID: 2520410377

Symbol: Q5TEH8_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q5TEH8

Database IDs:

ARBA 10 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 4 Gene3D 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 4 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 2 PROSITE 1 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 RuleBase 1 SMART 1 SMR 1 UCSC 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: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

Sequence Information:

  • Length: 299
  • Mass: 33945
  • Checksum: D6540DC48F592C09
  • Sequence:
    • MRSVGEGARE WIRECQHQFR HHRWNCTTLD RDHTVFGRVM LRSSREAAFV YAISSAGVVH 
AITRACSQGE LSVCSCDPYT RGRHHDQRGD FDWGGCSDNI HYGVRFAKAF VDAKEKRLKD 
ARALMNLHNN RCGRTAVRRF LKLECKCHGV SGSCTLRTCW RALSDFRRTG DYLRRRYDGA 
VQVMATQDGA NFTAARQGYR RATRTDLVYF DNSPDYCVLD KAAGSLGTAG RVCSKTSKGT 
DGCEIMCCGR GYDTTRVTRV TQCECKFHWC CAVRCKECRN TVDVHTCKAP KKAEWLDQT