The protein encoded by this gene is a connexin and is a component of lens fiber gap junctions. Defects in this gene are a cause of zonular pulverulent cataract type 3 (CZP3). [provided by RefSeq, Jan 2010] See more...

Aliases for GJA3 Gene

Aliases for GJA3 Gene

  • Gap Junction Protein Alpha 3 2 3 5
  • Gap Junction Protein, Alpha 3, 46kDa 2 3
  • Gap Junction Alpha-3 Protein 3 4
  • Connexin-46 3 4
  • Gap Junction Protein, Alpha 3, 46kDa (Connexin 46) 2
  • Gap Junction Protein, Alpha 3, 46kD (Connexin 46) 2
  • Gap Junction Alpha 3 3
  • Connexin 46 2
  • CTRCT14 3
  • CX46 3
  • CZP3 3
  • Cx46 4

External Ids for GJA3 Gene

Previous HGNC Symbols for GJA3 Gene

  • CZP3

Previous GeneCards Identifiers for GJA3 Gene

  • GC13M018696
  • GC13M014696
  • GC13M019646
  • GC13M018514
  • GC13M019614
  • GC13M020712
  • GC13M001517

Summaries for GJA3 Gene

Entrez Gene Summary for GJA3 Gene

  • The protein encoded by this gene is a connexin and is a component of lens fiber gap junctions. Defects in this gene are a cause of zonular pulverulent cataract type 3 (CZP3). [provided by RefSeq, Jan 2010]

GeneCards Summary for GJA3 Gene

GJA3 (Gap Junction Protein Alpha 3) is a Protein Coding gene. Diseases associated with GJA3 include Cataract 14, Multiple Types and Early-Onset Posterior Polar Cataract. Among its related pathways are Myometrial Relaxation and Contraction Pathways and Gap junction trafficking. Gene Ontology (GO) annotations related to this gene include gap junction channel activity. An important paralog of this gene is GJA8.

UniProtKB/Swiss-Prot Summary for GJA3 Gene

  • Structural component of lens fiber gap junctions (PubMed:30044662). Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells (By similarity). They are formed by the docking of two hexameric hemichannels, one from each cell membrane. Small molecules and ions diffuse from one cell to a neighboring cell via the central pore (PubMed:30044662).

Tocris Summary for GJA3 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 GJA3 Gene

Additional gene information for GJA3 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GJA3 Gene

Genomics for GJA3 Gene

GeneHancer (GH) Regulatory Elements for GJA3 Gene

Promoters and enhancers for GJA3 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
GH13J020159 Promoter/Enhancer 1.4 FANTOM5 Ensembl ENCODE 505.3 +0.6 584 2.4 USF1 ZBTB26 MEF2C EZH2 ZNF341 POLR2A MYC KLF9 SP2 MXI1 GJA3 lnc-ZMYM2-13 PSPC1 ZMYM5 piR-61101-129
GH13J020126 Enhancer 1.2 FANTOM5 ENCODE 17.2 +33.7 33686 2.2 ZNF217 CTCF POLR2G ZFX ZNF10 ZIC2 POLR2A ZBTB10 ZNF423 ZBTB26 lnc-ZMYM2-3 GJA3 PPIAP28 CRYL1 PARP4P2 ZMYM5 PSPC1 lnc-ZMYM2-8
GH13J020190 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE 12.6 -30.9 -30936 4.6 HNRNPK ZBTB10 ZNF423 ZBTB26 EZH2 ZNF341 RELA TCF12 ZNF316 SP2 GJB2 GJA3 ENSG00000279065 lnc-ZMYM2-10 piR-61184 lnc-ZMYM2-9
GH13J020118 Promoter/Enhancer 1.6 FANTOM5 ENCODE CraniofacialAtlas 8.4 +41.4 41417 3.7 ZNF217 TCF12 POLR2G USF1 ZFX ZIC2 CLOCK FOS ZNF423 REST LOC105370101 HSALNG0095509 GJA3 PSPC1 ZMYM2 CRYL1 ZMYM5
GH13J020141 Enhancer 0.6 Ensembl 10.1 +19.3 19284 1 EZH2 ZNF843 SCRT1 GLIS1 ZFP69B TRIM28 KLF10 ZNF366 ZBTB8A ZEB2 GJA3 lnc-ZMYM2-8 piR-61101-129
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GJA3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GJA3

Top Transcription factor binding sites by QIAGEN in the GJA3 gene promoter:
  • Bach2
  • CBF(2)
  • CBF-A
  • CBF-B
  • CP1A
  • HNF-3beta
  • NF-Y
  • POU2F1
  • POU2F1a
  • ZIC2

Genomic Locations for GJA3 Gene

Genomic Locations for GJA3 Gene
chr13:20,138,255-20,161,385
(GRCh38/hg38)
Size:
23,131 bases
Orientation:
Minus strand
chr13:20,712,394-20,735,188
(GRCh37/hg19)
Size:
22,795 bases
Orientation:
Minus strand

Genomic View for GJA3 Gene

Genes around GJA3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GJA3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GJA3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GJA3 Gene

Proteins for GJA3 Gene

  • Protein details for GJA3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y6H8-CXA3_HUMAN
    Recommended name:
    Gap junction alpha-3 protein
    Protein Accession:
    Q9Y6H8
    Secondary Accessions:
    • Q0VAB7
    • Q9H537

    Protein attributes for GJA3 Gene

    Size:
    435 amino acids
    Molecular mass:
    47410 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. Forms heteromeric channels with GJA8.

neXtProt entry for GJA3 Gene

Post-translational modifications for GJA3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GJA3 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for GJA3 Gene

Domains & Families for GJA3 Gene

Gene Families for GJA3 Gene

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

Protein Domains for GJA3 Gene

Blocks:
  • Connexin, N terminal
  • Gap junction alpha-3 protein signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GJA3 Gene

GenScript: Design optimal peptide antigens:
  • Connexin-46 (CXA3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y6H8

UniProtKB/Swiss-Prot:

CXA3_HUMAN :
  • Belongs to the connexin family. Alpha-type (group II) subfamily.
Family:
  • Belongs to the connexin family. Alpha-type (group II) subfamily.
genes like me logo Genes that share domains with GJA3: view

Function for GJA3 Gene

Molecular function for GJA3 Gene

UniProtKB/Swiss-Prot Function:
Structural component of lens fiber gap junctions (PubMed:30044662). Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells (By similarity). They are formed by the docking of two hexameric hemichannels, one from each cell membrane. Small molecules and ions diffuse from one cell to a neighboring cell via the central pore (PubMed:30044662).
GENATLAS Biochemistry:
gap junction protein,alpha 3,46kDa (connexin 46),expressed in lens,monomer of the connexon (six subunits including GJA3,GJA8,GJB1,GJB2))

Phenotypes From GWAS Catalog for GJA3 Gene

Gene Ontology (GO) - Molecular Function for GJA3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0055077 gap junction hemi-channel activity IDA 30044662
genes like me logo Genes that share ontologies with GJA3: view
genes like me logo Genes that share phenotypes with GJA3: view

Human Phenotype Ontology for GJA3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for GJA3 Gene

MGI Knock Outs for GJA3:

Animal Model Products

CRISPR Products

miRNA for GJA3 Gene

miRTarBase miRNAs that target GJA3

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GJA3

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for GJA3 Gene

Localization for GJA3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GJA3 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 GJA3 gene
Compartment Confidence
plasma membrane 5
extracellular 2
cytoskeleton 2
nucleus 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1
peroxisome 0

Gene Ontology (GO) - Cellular Components for GJA3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IEA --
GO:0005887 integral component of plasma membrane IDA 30044662
GO:0005921 gap junction IEA --
GO:0005922 connexin complex IDA 30044662
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with GJA3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GJA3 Gene

Pathways & Interactions for GJA3 Gene

genes like me logo Genes that share pathways with GJA3: view

Pathways by source for GJA3 Gene

1 GeneGo (Thomson Reuters) pathway for GJA3 Gene
  • Cell adhesion Gap junctions
1 Qiagen pathway for GJA3 Gene
  • Signaling in Gap Junctions

Gene Ontology (GO) - Biological Process for GJA3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007154 cell communication IEA --
GO:0007601 visual perception IEA --
GO:0055085 transmembrane transport IEA --
GO:1990349 gap junction-mediated intercellular transport IDA 30044662
genes like me logo Genes that share ontologies with GJA3: view

No data available for SIGNOR curated interactions for GJA3 Gene

Drugs & Compounds for GJA3 Gene

(10) Drugs for GJA3 Gene - From: DGIdb, IUPHAR, Tocris, and Novoseek

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

(2) Additional Compounds for GJA3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(5) Tocris Compounds for GJA3 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 GJA3: view

Transcripts for GJA3 Gene

mRNA/cDNA for GJA3 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 GJA3

Alternative Splicing Database (ASD) splice patterns (SP) for GJA3 Gene

No ASD Table

Relevant External Links for GJA3 Gene

GeneLoc Exon Structure for
GJA3

Expression for GJA3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GJA3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GJA3 Gene

This gene is overexpressed in Heart - Left Ventricle (x22.6), Heart - Atrial Appendage (x8.3), and Artery - Coronary (x4.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for GJA3 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GJA3

SOURCE GeneReport for Unigene cluster for GJA3 Gene:

Hs.130313

Evidence on tissue expression from TISSUES for GJA3 Gene

  • Eye(4.5)

Phenotype-based relationships between genes and organs from Gene ORGANizer for GJA3 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • cranial nerve
  • eye
  • head
General:
  • peripheral nervous system
genes like me logo Genes that share expression patterns with GJA3: view

No data available for Protein differential expression in normal tissues , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for GJA3 Gene

Orthologs for GJA3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for GJA3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GJA3 31 30
  • 99.39 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GJA3 31 30
  • 79.58 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Gja3 30
  • 78.44 (n)
mouse
(Mus musculus)
Mammalia Gja3 17 31 30
  • 78.24 (n)
cow
(Bos Taurus)
Mammalia GJA3 31 30
  • 76.72 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GJA3 31
  • 67 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GJA3 31
  • 63 (a)
OneToOne
chicken
(Gallus gallus)
Aves GJA3 31 30
  • 63.88 (n)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia gja3 30
  • 63.85 (n)
Str.5420 30
African clawed frog
(Xenopus laevis)
Amphibia MGC53082 30
zebrafish
(Danio rerio)
Actinopterygii gja3 31 30
  • 65.31 (n)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.2132 30
Species where no ortholog for GJA3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • 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 GJA3 Gene

ENSEMBL:
Gene Tree for GJA3 (if available)
TreeFam:
Gene Tree for GJA3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GJA3: view image

Paralogs for GJA3 Gene

(16) SIMAP similar genes for GJA3 Gene using alignment to 1 proteins:

  • CXA3_HUMAN
genes like me logo Genes that share paralogs with GJA3: view

Variants for GJA3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GJA3 Gene

SNP ID Clinical significance and condition Chr 13 pos Variation AA Info Type
16979 Pathogenic: Zonular pulverulent cataract 3 20,142,151(-) T/TG FRAMESHIFT_VARIANT
639312 Pathogenic: Zonular pulverulent cataract 3 20,143,159(-) C/T MISSENSE_VARIANT
654528 Uncertain Significance: Zonular pulverulent cataract 3 20,142,072(-) T/C MISSENSE_VARIANT
663670 Uncertain Significance: Zonular pulverulent cataract 3 20,143,043(-) G/C MISSENSE_VARIANT
743528 Likely Benign: not provided 20,142,202(-) C/CT FRAMESHIFT_VARIANT

Additional dbSNP identifiers (rs#s) for GJA3 Gene

Structural Variations from Database of Genomic Variants (DGV) for GJA3 Gene

Variant ID Type Subtype PubMed ID
esv2667874 CNV deletion 23128226
esv3631421 CNV gain 21293372
esv3631422 CNV gain 21293372
esv3631423 CNV loss 21293372
nsv1037299 CNV gain 25217958
nsv1046946 CNV gain 25217958
nsv1078303 OTHER inversion 25765185
nsv1140246 OTHER inversion 24896259
nsv1151909 OTHER inversion 26484159
nsv516427 CNV loss 19592680

Variation tolerance for GJA3 Gene

Gene Damage Index Score: 0.62; 13.40% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GJA3 Gene

Human Gene Mutation Database (HGMD)
GJA3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GJA3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GJA3 Gene

Disorders for GJA3 Gene

MalaCards: The human disease database

(17) MalaCards diseases for GJA3 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search GJA3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CXA3_HUMAN
  • Cataract 14, multiple types (CTRCT14) [MIM:601885]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT14 includes zonular pulverulent cataract, among others. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes. {ECO:0000269 PubMed:10205266, ECO:0000269 PubMed:10746562, ECO:0000269 PubMed:14627959, ECO:0000269 PubMed:15208569, ECO:0000269 PubMed:15286166, ECO:0000269 PubMed:15448617, ECO:0000269 PubMed:16234473, ECO:0000269 PubMed:16254549, ECO:0000269 PubMed:16885921, ECO:0000269 PubMed:16971895, ECO:0000269 PubMed:17615540, ECO:0000269 PubMed:17893674, ECO:0000269 PubMed:20431721, ECO:0000269 PubMed:21552498, ECO:0000269 PubMed:21647269, ECO:0000269 PubMed:21681855, ECO:0000269 PubMed:21897748, ECO:0000269 PubMed:22312188, ECO:0000269 PubMed:24772942, ECO:0000269 PubMed:25635993, ECO:0000269 PubMed:26683566, ECO:0000269 PubMed:30044662}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for GJA3

genes like me logo Genes that share disorders with GJA3: view

No data available for Genatlas for GJA3 Gene

Publications for GJA3 Gene

  1. Connexin46 mutations in autosomal dominant congenital cataract. (PMID: 10205266) Mackay D … Bhattacharya S (American journal of human genetics 1999) 2 3 4 23 54
  2. Mutation analysis of congenital cataract in a Chinese family identified a novel missense mutation in the connexin 46 gene (GJA3). (PMID: 20431721) Zhou Z … Qi Y (Molecular vision 2010) 3 4 23 54
  3. A novel "pearl box" cataract associated with a mutation in the connexin 46 (GJA3) gene. (PMID: 17615540) Guleria K … Singh JR (Molecular vision 2007) 3 4 23 54
  4. A novel mutation in the connexin 46 (GJA3) gene associated with autosomal dominant congenital cataract in an Indian family. (PMID: 17893674) Guleria K … Vanita V (Molecular vision 2007) 3 4 23 54
  5. A novel mutation in the connexin 46 gene (GJA3) causes autosomal dominant zonular pulverulent cataract in a Hispanic family. (PMID: 16885921) Addison PK … Bhattacharya SS (Molecular vision 2006) 3 4 23 54

Products for GJA3 Gene

Sources for GJA3 Gene