This gene encodes a transmembrane connexin protein that is a component of gap junctions. Mutations in this gene have been associated with erythrokeratodermia variabilis, progressive symmetric erythrokeratoderma and hearing impairment. [provided by RefSeq, Dec 2009] See more...

Aliases for GJB4 Gene

Aliases for GJB4 Gene

  • Gap Junction Protein Beta 4 2 3 5
  • Gap Junction Protein, Beta 4, 30.3kDa 2 3
  • Gap Junction Beta-4 Protein 3 4
  • Connexin 30.3 2 3
  • Gap Junction Protein, Beta 4 (Connexin 30.3) 2
  • Gap Junction Protein, Beta 4 2
  • Connexin-30.3 4
  • CX30.3 3
  • Cx30.3 4
  • EKVP2 3
  • EKV 3

External Ids for GJB4 Gene

Previous GeneCards Identifiers for GJB4 Gene

  • GC01U990071
  • GC01P034281
  • GC01P034651
  • GC00M9U0070
  • GC01P034894
  • GC01P034997
  • GC01P034999
  • GC01P035225
  • GC01P033342

Summaries for GJB4 Gene

Entrez Gene Summary for GJB4 Gene

  • This gene encodes a transmembrane connexin protein that is a component of gap junctions. Mutations in this gene have been associated with erythrokeratodermia variabilis, progressive symmetric erythrokeratoderma and hearing impairment. [provided by RefSeq, Dec 2009]

GeneCards Summary for GJB4 Gene

GJB4 (Gap Junction Protein Beta 4) is a Protein Coding gene. Diseases associated with GJB4 include Erythrokeratodermia Variabilis Et Progressiva 2 and Erythrokeratodermia Variabilis Et Progressiva 1. Among its related pathways are Vesicle-mediated transport and G-Beta Gamma Signaling. An important paralog of this gene is GJB5.

UniProtKB/Swiss-Prot Summary for GJB4 Gene

  • Structural component of gap junctions (By similarity). Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane (By similarity). Small molecules and ions diffuse from one cell to a neighboring cell via the central pore (By similarity).

Tocris Summary for GJB4 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 GJB4 Gene

Additional gene information for GJB4 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GJB4 Gene

Genomics for GJB4 Gene

GeneHancer (GH) Regulatory Elements for GJB4 Gene

Promoters and enhancers for GJB4 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
GH01J034759 Enhancer 0.6 Ensembl ENCODE dbSUPER 750.6 +0.1 61 1.2 GLIS1 GJB4 GJB5 RF01061-005 SMIM12
GH01J034841 Enhancer 1.4 Ensembl ENCODE CraniofacialAtlas dbSUPER 15 +85.0 84961 5.8 ZBTB40 RBPJ SMARCE1 NR2F6 RUNX1 CC2D1A ELF1 L3MBTL2 DACH1 TEAD4 ENSG00000230163 ZMYM1 TMEM35B GJB4 RPL5P4 LOC653160 CSMD2 GJA4 GJB3 SMIM12
GH01J034865 Promoter/Enhancer 1.4 ENCODE CraniofacialAtlas dbSUPER 10.5 +106.6 106568 1.6 CTCF NR2F6 MYC CC2D1A ZNF701 L3MBTL2 RAD21 TEAD4 POLR2A SP1 LOC653160 TMEM35B ZMYM1 ENSG00000230163 ZMYM6 SFPQ RPL5P4 GJB4 TFAP2E HSALNG0002454
GH01J034825 Enhancer 1.2 Ensembl ENCODE CraniofacialAtlas 10.6 +65.9 65861 1.2 FOXA1 RBPJ NR2F6 ZNF217 MNT RERE SP1 NCOA3 MYC SP5 GJB3 GJB4 SMIM12 hsa-miR-5095-012 piR-38344-002
GH01J034792 Promoter 0.9 EPDnew Ensembl 11 +35.5 35460 5.6 RUNX3 RFX5 VEZF1 PRDM10 GJA4 GJB5 GJB4 GJB3 piR-38344-002 SMIM12
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GJB4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the GJB4 gene promoter:
  • AP-2alpha
  • AP-2alphaA
  • AP-2beta
  • AP-2gamma
  • c-Myc
  • Max1
  • NF-1
  • NF-1/L

Genomic Locations for GJB4 Gene

Genomic Locations for GJB4 Gene
chr1:34,759,740-34,763,724
(GRCh38/hg38)
Size:
3,985 bases
Orientation:
Plus strand
chr1:35,225,342-35,229,325
(GRCh37/hg19)
Size:
3,984 bases
Orientation:
Plus strand

Genomic View for GJB4 Gene

Genes around GJB4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GJB4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GJB4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GJB4 Gene

Proteins for GJB4 Gene

  • Protein details for GJB4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NTQ9-CXB4_HUMAN
    Recommended name:
    Gap junction beta-4 protein
    Protein Accession:
    Q9NTQ9
    Secondary Accessions:
    • B3KQ82

    Protein attributes for GJB4 Gene

    Size:
    266 amino acids
    Molecular mass:
    30419 Da
    Quaternary structure:
    • A hemichannel or connexon is composed of a hexamer of connexins. A functional gap junction is formed by the apposition of two hemichannels (By similarity). Forms heteromeric channels with GJB2 (By similarity).

neXtProt entry for GJB4 Gene

Post-translational modifications for GJB4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GJB4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for GJB4 Gene

Domains & Families for GJB4 Gene

Gene Families for GJB4 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted membrane proteins

Suggested Antigen Peptide Sequences for GJB4 Gene

GenScript: Design optimal peptide antigens:
  • Connexin-30.3 (CXB4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NTQ9

UniProtKB/Swiss-Prot:

CXB4_HUMAN :
  • Belongs to the connexin family. Beta-type (group I) subfamily.
Family:
  • Belongs to the connexin family. Beta-type (group I) subfamily.
genes like me logo Genes that share domains with GJB4: view

Function for GJB4 Gene

Molecular function for GJB4 Gene

UniProtKB/Swiss-Prot Function:
Structural component of gap junctions (By similarity). Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane (By similarity). Small molecules and ions diffuse from one cell to a neighboring cell via the central pore (By similarity).

Phenotypes From GWAS Catalog for GJB4 Gene

Gene Ontology (GO) - Molecular Function for GJB4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005243 gap junction channel activity ISS --
genes like me logo Genes that share ontologies with GJB4: view
genes like me logo Genes that share phenotypes with GJB4: view

Human Phenotype Ontology for GJB4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for GJB4 Gene

MGI Knock Outs for GJB4:
  • Gjb4 Gjb4<tm1.1(KOMP)Vlcg>
  • Gjb4 Gjb4<tm1Kwi>

Animal Model Products

CRISPR Products

miRNA for GJB4 Gene

miRTarBase miRNAs that target GJB4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GJB4

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for GJB4 Gene

Localization for GJB4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GJB4 Gene

Cell membrane; Multi-pass membrane protein. Cell junction, gap junction. Note=Colocalizes with GJB2 at gap junction plaques in the cochlea. {ECO:0000250 UniProtKB:Q02738}.

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 GJB4 gene
Compartment Confidence
plasma membrane 5
nucleus 4
extracellular 0
lysosome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for GJB4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005730 nucleolus IDA --
GO:0005886 plasma membrane IEA --
GO:0005887 integral component of plasma membrane ISS,IEA --
GO:0005921 gap junction IEA --
genes like me logo Genes that share ontologies with GJB4: view

Pathways & Interactions for GJB4 Gene

genes like me logo Genes that share pathways with GJB4: view

Pathways by source for GJB4 Gene

1 Qiagen pathway for GJB4 Gene
  • Signaling in Gap Junctions

Gene Ontology (GO) - Biological Process for GJB4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007154 cell communication IEA --
GO:0007267 cell-cell signaling IEA,ISS --
GO:0007608 sensory perception of smell IEA --
GO:0042048 olfactory behavior IEA --
GO:0055085 transmembrane transport IEA --
genes like me logo Genes that share ontologies with GJB4: view

No data available for SIGNOR curated interactions for GJB4 Gene

Drugs & Compounds for GJB4 Gene

(9) Drugs for GJB4 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 1
Carbenoxolone Experimental Pharma Inhibitor 0
octanol Investigational Pharma Inhibitor 0
Ca<sup>2+</sup> Pharma Activator, Full agonist, 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 GJB4 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 GJB4: view

Transcripts for GJB4 Gene

mRNA/cDNA for GJB4 Gene

(1) REFSEQ mRNAs :
(2) Additional mRNA sequences :
(6) Selected AceView cDNA sequences:
(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 GJB4

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for GJB4 Gene

No ASD Table

Relevant External Links for GJB4 Gene

GeneLoc Exon Structure for
GJB4
ECgene alternative splicing isoforms for
GJB4

Expression for GJB4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for GJB4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GJB4 Gene

This gene is overexpressed in Skin - Sun Exposed (Lower leg) (x23.1) and Skin - Not Sun Exposed (Suprapubic) (x21.8).

NURSA nuclear receptor signaling pathways regulating expression of GJB4 Gene:

GJB4

SOURCE GeneReport for Unigene cluster for GJB4 Gene:

Hs.351203

Evidence on tissue expression from TISSUES for GJB4 Gene

  • Skin(4.5)

Phenotype-based relationships between genes and organs from Gene ORGANizer for GJB4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • endocrine
  • immune
  • integumentary
  • nervous
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • ear
  • eye
  • head
  • skull
Thorax:
  • heart
Abdomen:
  • kidney
  • pancreas
Limb:
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • nail
  • upper limb
General:
  • blood
  • blood vessel
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • sweat gland
genes like me logo Genes that share expression patterns with GJB4: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for GJB4 Gene

Orthologs for GJB4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for GJB4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GJB4 33 32
  • 98.5 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GJB4 33 32
  • 86.72 (n)
OneToOne
cow
(Bos Taurus)
Mammalia GJB4 33 32
  • 85.84 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Gjb4 32
  • 84.65 (n)
mouse
(Mus musculus)
Mammalia Gjb4 17 33 32
  • 83.21 (n)
oppossum
(Monodelphis domestica)
Mammalia GJB4 33
  • 72 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GJB4 33
  • 68 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100486331 32
  • 64.19 (n)
zebrafish
(Danio rerio)
Actinopterygii cx34.4 33 32
  • 63.72 (n)
ManyToMany
cx28.6 33
  • 55 (a)
ManyToMany
cx30.9 33
  • 50 (a)
ManyToMany
Species where no ortholog for GJB4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • chicken (Gallus gallus)
  • 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)
  • lizard (Anolis carolinensis)
  • 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 squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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 GJB4 Gene

ENSEMBL:
Gene Tree for GJB4 (if available)
TreeFam:
Gene Tree for GJB4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GJB4: view image

Paralogs for GJB4 Gene

(17) SIMAP similar genes for GJB4 Gene using alignment to 1 proteins:

  • CXB4_HUMAN
genes like me logo Genes that share paralogs with GJB4: view

Variants for GJB4 Gene

Sequence variations from dbSNP and Humsavar for GJB4 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs146378222 uncertain-significance, Deafness, autosomal dominant 3a, Deafness, autosomal recessive 1A 34,761,363(+) G/A coding_sequence_variant, missense_variant
rs148182439 likely-pathogenic, Erythrokeratodermia variabilis 34,761,640(+) G/A coding_sequence_variant, stop_gained
rs3738346 benign, not specified, - 34,761,865(+) A/C coding_sequence_variant, missense_variant
rs79193415 benign, not specified, - 34,761,761(+) C/A/G/T coding_sequence_variant, missense_variant, stop_gained, synonymous_variant
rs80358206 pathogenic, Erythrokeratodermia variabilis et progressiva 2, Erythrokeratodermia variabilis et progressiva 2 (EKVP2) [MIM:617524] 34,761,665(+) C/A/T coding_sequence_variant, missense_variant, synonymous_variant

Structural Variations from Database of Genomic Variants (DGV) for GJB4 Gene

Variant ID Type Subtype PubMed ID
nsv947426 CNV duplication 23825009

Variation tolerance for GJB4 Gene

Residual Variation Intolerance Score: 98.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.85; 83.61% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GJB4 Gene

Human Gene Mutation Database (HGMD)
GJB4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GJB4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GJB4 Gene

Disorders for GJB4 Gene

MalaCards: The human disease database

(17) MalaCards diseases for GJB4 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search GJB4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CXB4_HUMAN
  • Erythrokeratodermia variabilis et progressiva 2 (EKVP2) [MIM:617524]: A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. {ECO:0000269 PubMed:11017804, ECO:0000269 PubMed:12648223, ECO:0000269 PubMed:19291775}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for GJB4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GJB4: view

No data available for Genatlas for GJB4 Gene

Publications for GJB4 Gene

  1. The missense mutation G12D in connexin30.3 can cause both erythrokeratodermia variabilis of Mendes da Costa and progressive symmetric erythrokeratodermia of Gottron. (PMID: 19291775) van Steensel MA … van Geel M (American journal of medical genetics. Part A 2009) 3 4 23 56
  2. Genetic heterogeneity in erythrokeratodermia variabilis: novel mutations in the connexin gene GJB4 (Cx30.3) and genotype-phenotype correlations. (PMID: 12648223) Richard G … Uitto J (The Journal of investigative dermatology 2003) 3 4 23 56
  3. A common frameshift mutation and other variants in GJB4 (connexin 30.3): Analysis of hearing impairment families. (PMID: 11933201) López-Bigas N … Estivill X (Human mutation 2002) 3 4 23 56
  4. Prospective variants screening of connexin genes in children with hearing impairment: genotype/phenotype correlation. (PMID: 20593197) Yang JJ … Li SY (Human genetics 2010) 3 43 56
  5. Association of genetic variants with chronic kidney disease in individuals with different lipid profiles. (PMID: 19578796) Yoshida T … Yamada Y (International journal of molecular medicine 2009) 3 43 56

Products for GJB4 Gene

Sources for GJB4 Gene