Connexins, such as GJD4, are involved in the formation of gap junctions, intercellular conduits that directly connect the cytoplasms of contacting cells. Each gap junction channel is formed by docking of 2 hemichannels, each of which contains 6 connexin subunits (Sohl et al., 2003 [PubMed 12881038]).[supplied by OMIM, Mar 2008] See more...

Aliases for GJD4 Gene

Aliases for GJD4 Gene

  • Gap Junction Protein Delta 4 2 3 5
  • CX40.1 2 3 4
  • Gap Junction Protein, Delta 4, 40.1kDa 2 3
  • Gap Junction Delta-4 Protein 3 4
  • Connexin-40.1 3 4
  • Connexin 40.1 2
  • Connexin40.1 3
  • FLJ90023 2
  • Cx40.1 4
  • GJD4 5

External Ids for GJD4 Gene

Previous GeneCards Identifiers for GJD4 Gene

  • GC10P035935
  • GC10P035894

Summaries for GJD4 Gene

Entrez Gene Summary for GJD4 Gene

  • Connexins, such as GJD4, are involved in the formation of gap junctions, intercellular conduits that directly connect the cytoplasms of contacting cells. Each gap junction channel is formed by docking of 2 hemichannels, each of which contains 6 connexin subunits (Sohl et al., 2003 [PubMed 12881038]).[supplied by OMIM, Mar 2008]

GeneCards Summary for GJD4 Gene

GJD4 (Gap Junction Protein Delta 4) is a Protein Coding gene. Diseases associated with GJD4 include Deafness, Autosomal Recessive 33 and Usher Syndrome, Type Ik. Among its related pathways are Gap junction trafficking and Vesicle-mediated transport. An important paralog of this gene is GJA8.

UniProtKB/Swiss-Prot Summary for GJD4 Gene

  • One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.

Tocris Summary for GJD4 Gene

  • Gap channels (gap junctions) are specialized cell-cell contacts that provide direct intracellular communication. They allow passive diffusion of molecules up to 1 kDa, including nutrients, metabolites (glucose), ions (K+, Ca2+) and second messengers (IP3, cAMP).

Gene Wiki entry for GJD4 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GJD4 Gene

Genomics for GJD4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for GJD4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10J035605 Promoter 0.7 EPDnew 600.7 +0.1 78 0.1 IKZF1 EHMT2 TAL1 TEAD4 CBFA2T2 RNF2 CBFA2T3 ARID1B GJD4 ENSG00000273312 FZD8
GH10J035578 Enhancer 0.6 Ensembl ENCODE 13 -27.2 -27240 1.8 ZNF316 MAFF MAFK DACH1 ZNF548 EMSY ENSG00000271335 GJD4 LOC107984221 piR-61945-041 CCNY
GH10J035550 Enhancer 0.4 Ensembl 11 -53.3 -53340 3.2 CEBPB CTCF RBM22 CREB1 ENSG00000271335 GJD4 piR-61945-041 HSALNG0077277 CCNY
GH10J035579 Enhancer 0.3 ENCODE 13 -25.4 -25407 0.4 ATF2 LOC107984221 ENSG00000271335 GJD4 piR-61945-041 CCNY
GH10J035626 Enhancer 0.2 Ensembl 11.8 +22.2 22160 1.8 GJD4 CUL2 ENSG00000287528 FZD8 ENSG00000273312
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GJD4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GJD4

Top Transcription factor binding sites by QIAGEN in the GJD4 gene promoter:
  • aMEF-2
  • HEN1
  • HSF1 (long)
  • HSF1short
  • MEF-2A
  • NRSF form 1
  • NRSF form 2
  • POU2F1a
  • RSRFC4
  • YY1

Genomic Locations for GJD4 Gene

Genomic Locations for GJD4 Gene
chr10:35,605,341-35,608,935
(GRCh38/hg38)
Size:
3,595 bases
Orientation:
Plus strand
chr10:35,894,338-35,897,863
(GRCh37/hg19)
Size:
3,526 bases
Orientation:
Plus strand

Genomic View for GJD4 Gene

Genes around GJD4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GJD4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GJD4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GJD4 Gene

Proteins for GJD4 Gene

  • Protein details for GJD4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96KN9-CXD4_HUMAN
    Recommended name:
    Gap junction delta-4 protein
    Protein Accession:
    Q96KN9
    Secondary Accessions:
    • Q8N2R7

    Protein attributes for GJD4 Gene

    Size:
    370 amino acids
    Molecular mass:
    40140 Da
    Quaternary structure:
    • A connexon is composed of a hexamer of connexins.

neXtProt entry for GJD4 Gene

Post-translational modifications for GJD4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GJD4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for GJD4 Gene

Domains & Families for GJD4 Gene

Gene Families for GJD4 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Predicted membrane proteins
  • Transporters

Protein Domains for GJD4 Gene

InterPro:
Blocks:
  • Connexin, N terminal
ProtoNet:

Suggested Antigen Peptide Sequences for GJD4 Gene

GenScript: Design optimal peptide antigens:
  • Connexin-40.1 (CXD4_HUMAN)
  • GJD4 protein (Q8IV12_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96KN9

UniProtKB/Swiss-Prot:

CXD4_HUMAN :
  • Belongs to the connexin family. Delta-type subfamily.
Family:
  • Belongs to the connexin family. Delta-type subfamily.
genes like me logo Genes that share domains with GJD4: view

Function for GJD4 Gene

Molecular function for GJD4 Gene

UniProtKB/Swiss-Prot Function:
One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.

Phenotypes From GWAS Catalog for GJD4 Gene

Gene Ontology (GO) - Molecular Function for GJD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005243 gap junction channel activity IBA 21873635
genes like me logo Genes that share ontologies with GJD4: view
genes like me logo Genes that share phenotypes with GJD4: view

Animal Models for GJD4 Gene

MGI Knock Outs for GJD4:
  • Gjd4 Gjd4<tm1.1Malt>
  • Gjd4 Gjd4<tm1.1(KOMP)Vlcg>

Animal Model Products

CRISPR Products

miRNA for GJD4 Gene

miRTarBase miRNAs that target GJD4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GJD4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GJD4 Gene

Localization for GJD4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GJD4 Gene

Cell membrane. Multi-pass membrane protein. Cell junction, gap junction.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GJD4 gene
Compartment Confidence
plasma membrane 4
extracellular 2
nucleus 1

Gene Ontology (GO) - Cellular Components for GJD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IEA --
GO:0005921 gap junction IEA --
GO:0005922 connexin complex IEA,IBA 21873635
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with GJD4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GJD4 Gene

Pathways & Interactions for GJD4 Gene

genes like me logo Genes that share pathways with GJD4: view

Gene Ontology (GO) - Biological Process for GJD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007154 cell communication IEA --
GO:0007267 cell-cell signaling IBA 21873635
GO:0014717 regulation of satellite cell activation involved in skeletal muscle regeneration IEA --
GO:0055085 transmembrane transport IEA --
genes like me logo Genes that share ontologies with GJD4: view

No data available for SIGNOR curated interactions for GJD4 Gene

Drugs & Compounds for GJD4 Gene

(9) Drugs for GJD4 Gene - From: DGIdb, IUPHAR, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Flufenamic acid Approved Pharma Channel blocker, Inhibitor, Pore Blocker, Antagonist Calcium-activated chloride channel blocker; NSAID. Also activates TRPC6 0
Carbenoxolone Experimental Pharma Inhibitor 0
octanol Investigational Pharma Inhibitor 0
Ca<sup>2+</sup> Pharma Activator, Agonist, Full agonist, Inhibitor, Antagonist, Channel blocker 0
10Panx Pharma Panx-1 mimetic inhibitor, Panx-1 mimetic inhibitory peptide; blocks pannexin-1 gap junctions 0

(5) Tocris Compounds for GJD4 Gene

Compound Action Cas Number
10Panx Panx-1 mimetic inhibitory peptide; blocks pannexin-1 gap junctions 955091-53-9
Carbenoxolone disodium Gap junction blocker. Also inhibitor of 11 beta-hydroxysteroid dehydrogenase 7421-40-1
Gap 26 Gap junction blocker; inhibits smooth muscle contraction and IP3-mediated ATP release 197250-15-0
Gap 27 Selective gap junction blocker 198284-64-9
Scrambled 10Panx Scrambled version of 10Panx (Cat. No. 3348), Panx-1 mimetic inhibitory peptide 1315378-72-3
genes like me logo Genes that share compounds with GJD4: view

Transcripts for GJD4 Gene

mRNA/cDNA for GJD4 Gene

1 REFSEQ mRNAs :
3 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GJD4

Alternative Splicing Database (ASD) splice patterns (SP) for GJD4 Gene

No ASD Table

Relevant External Links for GJD4 Gene

GeneLoc Exon Structure for
GJD4

Expression for GJD4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GJD4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GJD4 Gene

This gene is overexpressed in Brain - Frontal Cortex (BA9) (x7.8), Brain - Cortex (x7.4), and Brain - Anterior cingulate cortex (BA24) (x6.1).

Protein differential expression in normal tissues from HIPED for GJD4 Gene

This gene is overexpressed in Heart (38.2) and Platelet (30.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for GJD4 Gene



Protein tissue co-expression partners for GJD4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GJD4

SOURCE GeneReport for Unigene cluster for GJD4 Gene:

Hs.638922

mRNA Expression by UniProt/SwissProt for GJD4 Gene:

Q96KN9-CXD4_HUMAN
Tissue specificity: Expressed in pancreas, kidney, skeletal muscle, liver, placenta, and heart.
genes like me logo Genes that share expression patterns with GJD4: view

No data available for Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for GJD4 Gene

Orthologs for GJD4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for GJD4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia GJD4 30 31
  • 98.56 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia GJD4 30
  • 76.72 (n)
Cow
(Bos Taurus)
Mammalia GJD4 30 31
  • 69.13 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Gjd4 30
  • 63.76 (n)
Mouse
(Mus musculus)
Mammalia Gjd4 30 17 31
  • 63.76 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia GJD4 31
  • 63 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia GJD4 31
  • 43 (a)
OneToOne
Chicken
(Gallus gallus)
Aves GJD4 30 31
  • 59.61 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia GJD4 31
  • 56 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia MGC75599 30
Zebrafish
(Danio rerio)
Actinopterygii GJD4 31
  • 30 (a)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 20 (a)
OneToMany
-- 31
  • 17 (a)
OneToMany
Species where no ortholog for GJD4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for GJD4 Gene

ENSEMBL:
Gene Tree for GJD4 (if available)
TreeFam:
Gene Tree for GJD4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GJD4: view image

Paralogs for GJD4 Gene

(3) SIMAP similar genes for GJD4 Gene using alignment to 2 proteins:

  • CXD4_HUMAN
  • Q8IV12_HUMAN
genes like me logo Genes that share paralogs with GJD4: view

Variants for GJD4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GJD4 Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
rs773395724 A colorectal cancer sample p.Gly271Arg
VAR_037640 A colorectal cancer sample p.Arg269His
rs35398622 - p.Ala90Val

Additional dbSNP identifiers (rs#s) for GJD4 Gene

Structural Variations from Database of Genomic Variants (DGV) for GJD4 Gene

Variant ID Type Subtype PubMed ID
dgv1034n54 CNV loss 21841781
dgv144n67 CNV gain 20364138
esv2659329 CNV deletion 23128226
esv3622902 CNV loss 21293372
nsv466871 CNV loss 19166990
nsv825337 CNV gain 20364138

Variation tolerance for GJD4 Gene

Residual Variation Intolerance Score: 60.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.83; 47.92% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GJD4 Gene

Human Gene Mutation Database (HGMD)
GJD4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GJD4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GJD4 Gene

Disorders for GJD4 Gene

MalaCards: The human disease database

(4) MalaCards diseases for GJD4 Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search GJD4 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with GJD4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GJD4 Gene

Publications for GJD4 Gene

  1. Expression profiles of the novel human connexin genes hCx30.2, hCx40.1, and hCx62 differ from their putative mouse orthologues. (PMID: 12881038) Söhl G … Willecke K (Cell communication & adhesion 2003) 2 3 4
  2. Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries. (PMID: 16303743) Otsuki T … Isogai T (DNA research : an international journal for rapid publication of reports on genes and genomes 2005) 3 4
  3. A reference map of the human binary protein interactome. (PMID: 32296183) Luck K … Calderwood MA (Nature 2020) 3
  4. The absence of dysferlin induces the expression of functional connexin-based hemichannels in human myotubes. (PMID: 27229680) Cea LA … Caviedes P (BMC cell biology 2016) 3
  5. Connexin40 regulates platelet function. (PMID: 24096827) Vaiyapuri S … Gibbins JM (Nature communications 2013) 3

Products for GJD4 Gene

Sources for GJD4 Gene