Details for: HAPLN1

Gene ID: 1404

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: HAPLN1

Ensembl ID: ENSG00000145681

Description: hyaluronan and proteoglycan link protein 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • chondrocyte CL0000138
    CSI 14.11
    rCSI 22.44%
    PRS 92.63
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 7.2
    rCSI 12.09%
    PRS 87.9
  • sncg GABAergic cortical interneuron CL4023015
    CSI 5.6
    rCSI 9%
    PRS 88.76
  • interstitial cell of Cajal CL0002088
    CSI 4.86
    rCSI 6.18%
    PRS 97.46
  • inhibitory interneuron CL0000498
    CSI 4.54
    rCSI 10.48%
    PRS 89.78
  • stromal cell CL0000499
    CSI 4.47
    rCSI 12.58%
    PRS 93.28
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 4.23
    rCSI 5.27%
    PRS 86.04
  • neural crest cell CL0011012
    CSI 3.41
    rCSI 2.7%
    PRS 91.8
  • neural progenitor cell CL0011020
    CSI 2.87
    rCSI 12.64%
    PRS 87.37
  • basal cell of epidermis CL0002187
    CSI 1.99
    rCSI 3.53%
    PRS 72.17
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.74
    rCSI 5.45%
    PRS 90.02
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.35
    rCSI 2.38%
    PRS 87.44
  • forebrain radial glial cell CL0013000
    CSI 1.3
    rCSI 4.18%
    PRS 95.22
  • mesenchymal cell CL0008019
    CSI 1.14
    rCSI 2.89%
    PRS 92.96

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)

Loading network (please wait)...

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 [HAPLN1](/details-gene/1404) (Hyaluronan and Proteoglycan Link Protein 1) is a protein-coding gene located on chromosome 5q14.3. It encodes a crucial component of the extracellular matrix (ECM), responsible for stabilizing the interaction between hyaluronan and proteoglycans, particularly aggrecan. This function is essential for maintaining the structural integrity and compression resistance of tissues like cartilage ([Link](https://doi.org/10.1093/nar/18.5.1292)). Expression data highlights its predominant role in structural and neuronal contexts, with its highest significance observed in [chondrocytes](/details-cell/CL0000138). Additionally, [HAPLN1](/details-gene/1404) shows significant expression across various subtypes of GABAergic interneurons, suggesting a specialized role in the central nervous system, likely in the formation of perineuronal nets. ## Cellular Roles and Expression Landscape The expression profile of [HAPLN1](/details-gene/1404) underscores its dual importance in both skeletal and nervous systems. **Overall**, the gene's most significant expression is found in [chondrocytes](/details-cell/CL0000138) (CSI: 14.11), which is consistent with its well-established role as a cartilage link protein essential for joint health ([Link](https://doi.org/10.1016/0888-7543(90)90044-u)). Its high significance in these cells indicates it is a key functional workhorse for maintaining the biomechanical properties of cartilage. Expression in other cells of mesenchymal origin, such as [stromal cells](/details-cell/CL0000499) and [mesenchymal cells](/details-cell/CL0008019), further supports its broad role in connective tissue organization. A second major functional axis for [HAPLN1](/details-gene/1404) is within the central nervous system. It is a highly significant gene in multiple classes of [inhibitory interneurons](/details-cell/CL0000498), including [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011) (CSI: 7.20), [sncg GABAergic cortical interneurons](/details-cell/CL4023015) (CSI: 5.60), and [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) (CSI: 4.23). This expression pattern points towards a critical function in shaping neural circuits, likely through the organization of specialized ECM structures like perineuronal nets, which are known to regulate synaptic plasticity ([Link](https://doi.org/10.1006/bbrc.2000.3583)). Its presence in developmental cell types such as [neural crest cells](/details-cell/CL0011012) and [neural progenitor cells](/details-cell/CL0011020) is also consistent with its annotated roles in central nervous system development. ## Pathways and Molecular Function The molecular functions of [HAPLN1](/details-gene/1404) are centered on its role as a structural organizer within the extracellular space. Gene Ontology annotations confirm its participation in '[extracellular matrix organization](/details-go/GO0031012)' and as an '[extracellular matrix structural constituent conferring compression resistance](/details-go/GO0030021)'. This is achieved primarily through its '[hyaluronic acid binding](/details-go/GO0005540)' capability, which allows it to anchor large proteoglycan aggregates to the hyaluronan backbone, a process detailed in the '[Ecm proteoglycans](/details-reactome/R-HSA-3000178)' Reactome pathway. In the nervous system, these functions are specialized for the '[perineuronal net](/details-go/GO0072534)' and the '[synapse](/details-go/GO0045202)', where it contributes to the stability of the neuronal microenvironment. This involvement aligns with its GO-annotated roles in '[central nervous system development](/details-go/GO0007417)' and '[glial cell differentiation](/details-go/GO0010001)', suggesting that [HAPLN1](/details-gene/1404) helps to establish and maintain the intricate ECM architecture necessary for proper neuronal function and circuit maturation. ## Research Directions The dual-specialization of [HAPLN1](/details-gene/1404) in both cartilage biology and neuronal function presents unique research opportunities and potential therapeutic angles. Its function in ECM maintenance suggests a role in diseases characterized by matrix degradation, such as osteoarthritis and certain neurodegenerative or neurodevelopmental disorders. Based on the available data, several testable hypotheses can be proposed: 1. Dysregulation or reduced expression of [HAPLN1](/details-gene/1404) in [chondrocytes](/details-cell/CL0000138) is a primary event in the pathogenesis of osteoarthritis, leading to a loss of cartilage compressive strength and initiating a cascade of tissue degradation. 2. [HAPLN1](/details-gene/1404) is essential for the structural integrity of perineuronal nets surrounding GABAergic interneurons, and its absence impairs critical period plasticity and contributes to network hyperexcitability seen in conditions like epilepsy or schizophrenia. To test the second hypothesis regarding its role in neuronal function, a compelling experimental approach would be to use a Cre-lox system to generate a conditional knockout of [HAPLN1](/details-gene/1404) specifically in parvalbumin-expressing interneurons in mice. The integrity of perineuronal nets could be assessed using Wisteria floribunda agglutinin (WFA) staining, while cortical circuit function and plasticity could be measured via in vivo two-photon imaging and slice electrophysiology. From a therapeutic perspective, [HAPLN1](/details-gene/1404) is more likely a target for **activation** or supplementation rather than inhibition. For degenerative joint diseases, intra-articular injection of recombinant [HAPLN1](/details-gene/1404) could be explored as a strategy to restore ECM integrity and biomechanical function in damaged cartilage. Its role as a secreted, structural protein makes it a challenging but potentially valuable target for regenerative medicine approaches aimed at tissue repair.

Genular Protein ID: 4171422888

Symbol: HPLN1_HUMAN

Name: Hyaluronan and proteoglycan link protein 1

UniProtKB Accession Codes:

P10915 B2R9A9

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 5 Ensembl 1 ExpressionAtlas 1 GO 12 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 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 Reactome 1 RefSeq 4 SIGNOR 1 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: 2320422

Title: The primary structure of human cartilage link protein.

PubMed ID: 2320422

DOI: 10.1093/nar/18.5.1292

PubMed ID: 2336413

Title:

PubMed ID: 2336413

DOI: 10.1093/nar/18.8.2214

PubMed ID: 2286376

Title: Complete amino acid sequence of human cartilage link protein (CRTL1) deduced from cDNA clones and chromosomal assignment of the gene.

PubMed ID: 2286376

DOI: 10.1016/0888-7543(90)90044-u

PubMed ID: 2030970

Title: Characterization of the promoter for the rat and human link protein gene.

PubMed ID: 2030970

DOI: 10.1093/nar/19.8.1933

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: 11027579

Title: The brain link protein-1 (BRAL1): cDNA cloning, genomic structure, and characterization as a novel link protein expressed in adult brain.

PubMed ID: 11027579

DOI: 10.1006/bbrc.2000.3583

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: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 354
  • Mass: 40166
  • Checksum: 315C96EC3AC2626A
  • Sequence:
    • MKSLLLLVLI SICWADHLSD NYTLDHDRAI HIQAENGPHL LVEAEQAKVF SHRGGNVTLP 
CKFYRDPTAF GSGIHKIRIK WTKLTSDYLK EVDVFVSMGY HKKTYGGYQG RVFLKGGSDS 
DASLVITDLT LEDYGRYKCE VIEGLEDDTV VVALDLQGVV FPYFPRLGRY NLNFHEAQQA 
CLDQDAVIAS FDQLYDAWRG GLDWCNAGWL SDGSVQYPIT KPREPCGGQN TVPGVRNYGF 
WDKDKSRYDV FCFTSNFNGR FYYLIHPTKL TYDEAVQACL NDGAQIAKVG QIFAAWKILG 
YDRCDAGWLA DGSVRYPISR PRRRCSPTEA AVRFVGFPDK KHKLYGVYCF RAYN