Details for: GJB3

Gene ID: 2707

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: GJB3

Ensembl ID: ENSG00000188910

Description: gap junction protein beta 3

Cell Significance Landscape

Associated with

Significant Cells

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

  • respiratory basal cell CL0002633
    CSI 9.81
    rCSI 10.16%
    PRS 98.31
  • keratinocyte CL0000312
    CSI 7.5
    rCSI 6.29%
    PRS 97.11
  • secretory cell CL0000151
    CSI 4.82
    rCSI 5.03%
    PRS 97.61
  • stem cell CL0000034
    CSI 4.02
    rCSI 3.88%
    PRS 97.08
  • conjunctival epithelial cell CL1000432
    CSI 3.64
    rCSI 5.56%
    PRS 97.19
  • epithelial cell CL0000066
    CSI 3.3
    rCSI 5.06%
    PRS 91.7
  • respiratory hillock cell CL4030023
    CSI 2.68
    rCSI 4.78%
    PRS 98.73
  • respiratory suprabasal cell CL4033048
    CSI 2.58
    rCSI 3.31%
    PRS 98.41
  • colon epithelial cell CL0011108
    CSI 2.56
    rCSI 2.69%
    PRS 97.19
  • basal cell of prostate epithelium CL0002341
    CSI 2.36
    rCSI 6.84%
    PRS 98.01
  • club cell CL0000158
    CSI 2.18
    rCSI 3.2%
    PRS 96.78
  • corneal epithelial cell CL0000575
    CSI 1.88
    rCSI 5.39%
    PRS 97.87
  • epithelial cell of urethra CL1000296
    CSI 0.87
    rCSI 21.91%
    PRS 97.98

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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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 [GJB3](/details-gene/2707) (Gap Junction Protein Beta 3), also known as Connexin 31, is a protein-coding gene located on chromosome 1. It is a member of the connexin family of proteins that form gap junctions, which are intercellular channels facilitating direct communication and the exchange of ions and small molecules between adjacent cells. Functionally, [GJB3](/details-gene/2707) is integral to [cell-cell signaling](/details-gene/GO:0007267), particularly in the context of tissue development and homeostasis. Expression data highlights its significant role in epithelial and basal cell populations, with pronounced specificity in [respiratory basal cell](/details-cell/CL0002633) and [keratinocyte](/details-cell/CL0000312). Clinically, mutations in [GJB3](/details-gene/2707) are associated with hereditary skin disorders, such as Erythrokeratodermia Variabilis ([OMIM: 133200](https://omim.org/entry/133200)), and non-syndromic hearing impairment ([Link](https://doi.org/10.1038/3845)). ## Cellular Roles and Expression Landscape The expression profile of [GJB3](/details-gene/2707) strongly indicates a primary role in establishing and maintaining epithelial barriers across various tissues. **Overall**, the gene shows its highest significance in progenitor and structural cells that form these layers. The most significant expression is observed in [respiratory basal cell](/details-cell/CL0002633) (CSI: 9.81), which are the stem cells of the airway epithelium, suggesting a fundamental role for [GJB3](/details-gene/2707) in the regeneration and maintenance of the respiratory tract lining. This is complemented by its high significance in other respiratory cell types, including [respiratory hillock cell](/details-cell/CL4030023) and [club cell](/details-cell/CL0000158). A second major site of expression is the skin, evidenced by a very high CSI in [keratinocyte](/details-cell/CL0000312) (CSI: 7.50). This aligns with the gene's known involvement in skin development and pathology. The broader pattern of high expression in diverse epithelial populations, including [conjunctival epithelial cell](/details-cell/CL1000432), [colon epithelial cell](/details-cell/CL0011108), [basal cell of prostate epithelium](/details-cell/CL0002341), and [corneal epithelial cell](/details-cell/CL0000575), underscores its general importance in tissues that require robust cell-cell adhesion and coordinated communication for barrier function. The high ranking in [stem cell](/details-cell/CL0000034) further supports a role in undifferentiated, progenitor cell compartments responsible for tissue homeostasis. ## Pathways and Molecular Function The molecular functions of [GJB3](/details-gene/2707) are centered on its role as a structural component of gap junctions. Gene Ontology annotations confirm its involvement in [gap junction channel activity](/details-gene/GO:0005243) and its localization to the [connexin complex](/details-gene/GO:0005922) and the [gap junction](/details-gene/GO:0005921) itself. These structures are critical for [transmembrane transport](/details-gene/GO:0055085) and direct [cell-cell signaling](/details-gene/GO:0007267), enabling coordinated cellular responses within a tissue. Reactome pathway analysis further refines this role, placing [GJB3](/details-gene/2707) within the processes of [Gap junction assembly](/details-gene/R-HSA-190861) and [Gap junction trafficking and regulation](/details-gene/R-HSA-157858). This is highly consistent with its observed expression in keratinocytes, as it is a key component of the [Differentiation of keratinocytes in interfollicular epidermis in mammalian skin](/details-gene/R-HSA-9725554) pathway. Its annotation in broader biological processes such as [skin development](/details-gene/GO:0043588) and [developmental biology](/details-gene/R-HSA-1266738) aligns with its high expression in basal and stem cell populations that drive organogenesis and tissue maintenance. The link to [cellular response to retinoic acid](/details-gene/GO:0071300) suggests a potential mechanism through which its expression may be regulated during differentiation processes. ## Research Directions The established link between [GJB3](/details-gene/2707) mutations and both skin and hearing pathologies provides a clear direction for further research into the shared physiological mechanisms in these distinct tissues. **Testable Hypotheses:** 1. Given its high expression in [respiratory basal cell](/details-cell/CL0002633) and [keratinocyte](/details-cell/CL0000312), it can be hypothesized that [GJB3](/details-gene/2707) is essential for coordinating the collective migration and proliferation required for epithelial wound repair. A loss of its function may lead to delayed wound closure and compromised barrier restoration in both the skin and airway. 2. The dual phenotype of skin disease and deafness associated with certain [GJB3](/details-gene/2707) mutations ([Link](https://doi.org/10.1038/sj.ejhg.5200407)) suggests a shared physiological requirement in the inner ear and epidermis. It is hypothesized that [GJB3](/details-gene/2707)-mediated gap junctions are critical for potassium ion recycling in both the cochlea's organ of Corti and the human epidermis, and that pathogenic mutations disrupt this ion homeostasis, leading to both hearing loss and skin abnormalities. **Proposed Experiment:** To test the first hypothesis regarding wound healing, a robust in vitro experiment could be designed. Primary human keratinocytes would be cultured to confluence to form a monolayer. [GJB3](/details-gene/2707) expression would then be silenced using a lentiviral-based shRNA system, with a non-targeting shRNA serving as a control. A scratch wound assay would be performed on both the knockdown and control monolayers. The rate of wound closure would be quantified over 48 hours using live-cell imaging and automated image analysis. Concurrently, intercellular communication could be assessed via a dye-transfer assay (e.g., Lucifer yellow) to confirm the functional disruption of gap junctions. A significant delay in wound closure in the [GJB3](/details-gene/2707)-deficient cells would support the hypothesis. **Therapeutic Potential:** As [GJB3](/details-gene/2707)-related diseases are typically monogenic disorders resulting from loss-of-function or dominant-negative mutations, the gene itself is not a conventional target for inhibition. Instead, therapeutic strategies would likely focus on restoring or correcting its function. For recessive loss-of-function mutations causing deafness ([Link](https://doi.org/10.1093/hmg/9.1.63)), gene replacement therapy delivered to the inner ear could be a viable long-term strategy. For skin disorders caused by dominant-negative mutations, approaches like allele-specific silencing using siRNA or antisense oligonucleotides could be explored to selectively suppress the mutant allele. Small molecule chaperones or potentiators that aim to correct the misfolding or enhance the channel activity of specific mutant proteins may also represent a promising, though challenging, therapeutic avenue.

Genular Protein ID: 3105090253

Symbol: CXB3_HUMAN

Name: Gap junction beta-3 protein

UniProtKB Accession Codes:

O75712 B2R790 Q2TAZ8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 2 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 4 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 2 SMART 2 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9704026

Title: Human gap junction protein connexin31: molecular cloning and expression analysis.

PubMed ID: 9704026

DOI: 10.1006/bbrc.1998.9070

PubMed ID: 9843209

Title: Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis.

PubMed ID: 9843209

DOI: 10.1038/3840

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: 9843210

Title: Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment.

PubMed ID: 9843210

DOI: 10.1038/3845

PubMed ID: 10594760

Title: Identification of a novel mutation R42P in the gap junction protein beta-3 associated with autosomal dominant erythrokeratoderma variabilis.

PubMed ID: 10594760

DOI: 10.1046/j.1523-1747.1999.00792.x

PubMed ID: 10757647

Title: Connexin mutations associated with palmoplantar keratoderma and profound deafness in a single family.

PubMed ID: 10757647

DOI: 10.1038/sj.ejhg.5200407

PubMed ID: 10798362

Title: The spectrum of mutations in erythrokeratodermias -- novel and de novo mutations in GJB3.

PubMed ID: 10798362

DOI: 10.1007/s004390051045

PubMed ID: 10587579

Title: Mutations in connexin31 underlie recessive as well as dominant non-syndromic hearing loss.

PubMed ID: 10587579

DOI: 10.1093/hmg/9.1.63

PubMed ID: 10790215

Title: Identification of seven novel SNPS (five nucleotide and two amino acid substitutions) in the connexin31 (GJB3) gene.

PubMed ID: 10790215

DOI: 10.1002/(sici)1098-1004(200005)15:5<481::aid-humu15>3.0.co;2-7

PubMed ID: 19283857

Title: Connexin mutations in Brazilian patients with skin disorders with or without hearing loss.

PubMed ID: 19283857

DOI: 10.1002/ajmg.a.32765

Sequence Information:

  • Length: 270
  • Mass: 30818
  • Checksum: E46D36E5835646A4
  • Sequence:
    • MDWKTLQALL SGVNKYSTAF GRIWLSVVFV FRVLVYVVAA ERVWGDEQKD FDCNTKQPGC 
TNVCYDNYFP ISNIRLWALQ LIFVTCPSLL VILHVAYREE RERRHRQKHG DQCAKLYDNA 
GKKHGGLWWT YLFSLIFKLI IEFLFLYLLH TLWHGFNMPR LVQCANVAPC PNIVDCYIAR 
PTEKKIFTYF MVGASAVCIV LTICELCYLI CHRVLRGLHK DKPRGGCSPS SSASRASTCR 
CHHKLVEAGE VDPDPGNNKL QASAPNLTPI