Details for: HAPLN3

Gene ID: 145864

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: HAPLN3

Ensembl ID: ENSG00000140511

Description: hyaluronan and proteoglycan link protein 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • extravillous trophoblast CL0008036
    CSI 26.07
    rCSI 32.25%
    PRS 83.14
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 5.3
    rCSI 4.25%
    PRS 93.91
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 4.72
    rCSI 2.79%
    PRS 96.48
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 4.42
    rCSI 5.33%
    PRS 91.22
  • blood vessel endothelial cell CL0000071
    CSI 4.35
    rCSI 9.03%
    PRS 82
  • mature alpha-beta T cell CL0000791
    CSI 4.13
    rCSI 14.94%
    PRS 96.52
  • keratinocyte CL0000312
    CSI 3.88
    rCSI 3.26%
    PRS 86.75
  • naive T cell CL0000898
    CSI 3.11
    rCSI 2.16%
    PRS 95.46
  • cerebral cortex endothelial cell CL1001602
    CSI 3.09
    rCSI 5.34%
    PRS 77.35
  • basal cell CL0000646
    CSI 2.83
    rCSI 3.79%
    PRS 82.6
  • pulmonary capillary endothelial cell CL4028001
    CSI 2.83
    rCSI 5.39%
    PRS 92.26
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 2.58
    rCSI 2.53%
    PRS 94.99
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.49
    rCSI 1.79%
    PRS 94.92
  • epithelial cell CL0000066
    CSI 2.22
    rCSI 3.42%
    PRS 73.51
  • basal cell of prostate epithelium CL0002341
    CSI 2.14
    rCSI 6.19%
    PRS 89.32
  • vascular associated smooth muscle cell CL0000359
    CSI 1.96
    rCSI 6.37%
    PRS 82.86
  • retinal rod cell CL0000604
    CSI 1.94
    rCSI 3.41%
    PRS 80.27
  • chondrocyte CL0000138
    CSI 1.76
    rCSI 2.79%
    PRS 78.53
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.74
    rCSI 1.68%
    PRS 84.07
  • tendon cell CL0000388
    CSI 1.6
    rCSI 4.16%
    PRS 89.4
  • mammary gland epithelial cell CL0002327
    CSI 1.16
    rCSI 4.06%
    PRS 90.85
  • follicular dendritic cell CL0000442
    CSI 1.01
    rCSI 16.17%
    PRS 91.72
  • vein endothelial cell of respiratory system CL4033008
    CSI 0.86
    rCSI 5.94%
    PRS 89.44
  • prostate gland microvascular endothelial cell CL2000059
    CSI 0.63
    rCSI 15.05%
    PRS 90.54

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 [HAPLN3](/details-gene/145864), or hyaluronan and proteoglycan link protein 3, is a protein-coding gene located on chromosome 15q26.1. As a member of the hyaluronan and proteoglycan link protein family, its primary molecular function is [hyaluronic acid binding](/details-go/GO:0005540), which is critical for organizing and stabilizing the extracellular matrix (ECM). **Overall**, expression analysis reveals that [HAPLN3](/details-gene/145864) is an exceptionally strong and specific marker for the [extravillous trophoblast](/details-cell/CL0008036) (CSI: 26.07), a cell type essential for placental implantation and maternal-fetal interface integrity. The gene also shows moderate but consistent significance in various immune populations, including [CD4-positive, alpha-beta thymocytes](/details-cell/CL0000810) and [central memory CD4-positive, alpha-beta T cells](/details-cell/CL0000904), as well as in endothelial cells, suggesting broader roles in cell adhesion and tissue structure. ## Cellular Roles and Expression Landscape The expression profile of [HAPLN3](/details-gene/145864) is dominated by its highly specific and abundant expression in the [extravillous trophoblast](/details-cell/CL0008036), indicating a specialized and potentially critical role in placental development and function. This unique cellular context suggests its involvement in the extensive tissue remodeling and invasion processes required for successful pregnancy. Beyond this primary role, [HAPLN3](/details-gene/145864) demonstrates a consistent pattern of expression across several functionally related cell types, albeit at much lower levels. It is significantly expressed in a wide range of T-lymphocytes, including [CD4-positive, alpha-beta thymocytes](/details-cell/CL0000810), [central memory CD4-positive, alpha-beta T cells](/details-cell/CL0000904), [mature alpha-beta T cells](/details-cell/CL0000791), and [regulatory T cells](/details-cell/CL0000792). This, combined with its expression in [CD1c-positive myeloid dendritic cells](/details-cell/CL0002399), points towards a function in the immune system, possibly related to lymphocyte trafficking, activation, or interaction with the ECM in lymphoid tissues or sites of inflammation. Furthermore, its significance in various endothelial cell populations, such as [blood vessel endothelial cells](/details-cell/CL0000071) and [cerebral cortex endothelial cells](/details-cell/CL1001602), suggests a contribution to vascular integrity and the structure of the blood vessel wall. Expression in epithelial cells like [keratinocytes](/details-cell/CL0000312) and [basal cells](/details-cell/CL0000646) further supports its general role in maintaining tissue architecture through ECM stabilization. ## Pathways and Molecular Function Functionally, [HAPLN3](/details-gene/145864) is an extracellular protein that plays a key structural role in the ECM. Its molecular function is defined by [hyaluronic acid binding](/details-go/GO:0005540), which allows it to act as a "link protein" that crosslinks hyaluronic acid with proteoglycans, thereby stabilizing the ECM network. This biochemical activity is central to the biological process of [cell adhesion](/details-go/GO:0007155), consistent with its expression in invasive trophoblasts, mobile immune cells, and tissue-lining endothelial and epithelial cells. Gene Ontology annotations also point to roles in development, including [skeletal system development](/details-go/GO:0001501) and [central nervous system development](/details-go/GO:0007417). The latter is supported by its annotated localization to the [perineuronal net](/details-go/GO:0072534) and the [synapse](/details-go/GO:0045202). However, the provided expression data does not show high significance in neuronal or glial cell types, suggesting that its role in the CNS may be confined to specific developmental stages or highly specialized cellular microenvironments not prominently represented in the dataset. A foundational study characterized this gene family as the "missing links" that physically connect proteoglycan core proteins to the hyaluronan backbone of the ECM ([Link](https://doi.org/10.1074/jbc.m213100200)). ## Research Directions The highly specific expression pattern and established molecular function of [HAPLN3](/details-gene/145864) give rise to several testable hypotheses regarding its physiological and pathological roles. 1. **Hypothesis on Placentation:** Given its overwhelming expression in [extravillous trophoblasts](/details-cell/CL0008036), [HAPLN3](/details-gene/145864) is hypothesized to be essential for proper trophoblast invasion and uterine artery remodeling. Dysregulation of [HAPLN3](/details-gene/145864) expression or function could therefore be a key factor in pregnancy complications such as pre-eclampsia, fetal growth restriction, or placenta accreta. 2. **Hypothesis on Immune Cell Trafficking:** The expression of [HAPLN3](/details-gene/145864) across T cell and dendritic cell lineages suggests it may play a role in mediating immune cell adhesion and migration through hyaluronan-rich tissues. It could function to either retain leukocytes in lymphoid organs or facilitate their extravasation into inflamed tissues. 3. **Hypothesis on Vascular Barrier Function:** Its presence in endothelial cells implies that [HAPLN3](/details-gene/145864) contributes to the integrity of the vascular basement membrane. A loss of function could lead to increased vascular permeability, while overexpression might contribute to pathological vascular stiffening or fibrosis. To investigate the primary hypothesis concerning its role in placentation, a key experiment would be to use CRISPR-Cas9 to knock out [HAPLN3](/details-gene/145864) in a human extravillous trophoblast cell line (e.g., HTR-8/SVneo). The functional consequences could be assessed using in vitro models, including Matrigel transwell assays to measure invasive capacity and co-culture systems with uterine endothelial or stromal cells to evaluate its role in cell-cell interactions and tissue integration. From a therapeutic standpoint, the extreme specificity of [HAPLN3](/details-gene/145864) for [extravillous trophoblasts](/details-cell/CL0008036) makes it a compelling diagnostic biomarker for placental health, where its levels could be monitored in maternal circulation. As a secreted protein, it is also a potential therapeutic target. For conditions of insufficient trophoblast invasion, a recombinant [HAPLN3](/details-gene/145864) protein could be explored, whereas in diseases of excessive invasion like placenta accreta, a neutralizing antibody targeting [HAPLN3](/details-gene/145864) could represent a highly specific therapeutic strategy to limit placental over-adherence.

Genular Protein ID: 2857583900

Symbol: HPLN3_HUMAN

Name: Hyaluronan and proteoglycan link protein 3

UniProtKB Accession Codes:

Q96S86 A8K7P0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 3 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 9 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 2 SMART 3 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12663660

Title: A hyaluronan binding link protein gene family whose members are physically linked adjacent to chondroitin sulfate proteoglycan core protein genes: the missing links.

PubMed ID: 12663660

DOI: 10.1074/jbc.m213100200

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

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

Sequence Information:

  • Length: 360
  • Mass: 40894
  • Checksum: 3B72AE88D0D9E8DC
  • Sequence:
    • MGLLLLVPLL LLPGSYGLPF YNGFYYSNSA NDQNLGNGHG KDLLNGVKLV VETPEETLFT 
YQGASVILPC RYRYEPALVS PRRVRVKWWK LSENGAPEKD VLVAIGLRHR SFGDYQGRVH 
LRQDKEHDVS LEIQDLRLED YGRYRCEVID GLEDESGLVE LELRGVVFPY QSPNGRYQFN 
FHEGQQVCAE QAAVVASFEQ LFRAWEEGLD WCNAGWLQDA TVQYPIMLPR QPCGGPGLAP 
GVRSYGPRHR RLHRYDVFCF ATALKGRVYY LEHPEKLTLT EAREACQEDD ATIAKVGQLF 
AAWKFHGLDR CDAGWLADGS VRYPVVHPHP NCGPPEPGVR SFGFPDPQSR LYGVYCYRQH

Genular Protein ID: 1878534574

Symbol: H3BTH8_HUMAN

Name: N/A

UniProtKB Accession Codes:

H3BTH8

Database IDs:

ARBA 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 3 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 2 Gene3D 2 GeneTree 1 HGNC 1 InterPro 9 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 5 PROSITE-ProRule 1 PeptideAtlas 2 Pfam 2 PhylomeDB 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 SMART 3 SMR 1 SUPFAM 2 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: 16572171

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

PubMed ID: 16572171

DOI: 10.1038/nature04601

Sequence Information:

  • Length: 422
  • Mass: 47757
  • Checksum: 7E62266086FF22B4
  • Sequence:
    • MRKWRHREVN LPEVTQQDAV CPAPIPSPGL SAQTGLQKIW GTIHCQVCPG APAWPGSPWH 
EEMGLLLLVP LLLLPGSYGL PFYNGFYYSN SANDQNLGNG HGKDLLNGVK LVVETPEETL 
FTYQGASVIL PCRYRYEPAL VSPRRVRVKW WKLSENGAPE KDVLVAIGLR HRSFGDYQGR 
VHLRQDKEHD VSLEIQDLRL EDYGRYRCEV IDGLEDESGL VELELRGVVF PYQSPNGRYQ 
FNFHEGQQVC AEQAAVVASF EQLFRAWEEG LDWCNAGWLQ DATVQYPIML PRQPCGGPGL 
APGVRSYGPR HRRLHRYDVF CFATALKGRV YYLEHPEKLT LTEAREACQE DDATIAKVGQ 
LFAAWKFHGL DRCDAGWLAD GSVRYPVVHP HPNCGPPEPG VRSFGFPDPQ SRLYGVYCYR 
QH

Genular Protein ID: 215863244

Symbol: A8K7T8_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K7T8

Database IDs:

ARBA 1 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 3 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 Gene3D 2 InterPro 9 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 5 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 2 RefSeq 2 SAM 1 SMART 3 SUPFAM 2

Sequence Information:

  • Length: 360
  • Mass: 40924
  • Checksum: 3B72B438D0D9E8CD
  • Sequence:
    • MGLLLLVPLL LLPGSYGLPF YNGFYYSNSA NDQNLGNGHG KDLLNGVKLV VETPEETLFT 
YQGASVILPC RYRYEPALVS PRRVRVKWWK LSENGAPEKD VLVAIGLRHR SFGDYQGRVH 
LRQDKEHDVS LEIQDLRLED YGRYRCEVID GLEDESGLVE LELRGVVFPY QSPNGRYQFN 
FHEGQQVCAE QAAVVASFEQ LFRAWEEGLD WCNAGWLQDA TVQYPIMLPR QPCGGPGLAP 
GVRSYGPRHR RLHRYDVFCF ATALKGRVYY LEHPEKLTLT EAREACQEDD ATIAKVGQLF 
AAWKFHGLDR CDTGWLADGS VRYPVVHPHP NCGPPEPGVR SFGFPDPQSR LYGVYCYRQH