GJA1

Protein identityUniProt · HPA

UniProt accession

P17302

Gene

GJA1

Ensembl

ENSG00000152661

Chromosome

6

Canonical length

382 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Potential drug targets, Predicted membrane proteins, Transporters

Subcellular location

Nucleoplasm,Vesicles,Cell Junctions

OverviewNCBI Gene

This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. The encoded protein is the major protein of gap junctions in the heart that are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. A related intronless pseudogene has been mapped to chromosome 5. Mutations in this gene have been associated with oculodentodigital dysplasia, autosomal recessive craniometaphyseal dysplasia and heart malformations. [provided by RefSeq, May 2014]

Canonical amino-acid sequenceUniProt

382 residues, UniProt reviewed canonical sequence.

>P17302|GJA1
     1  MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS AFRCNTQQPG
    61  CENVCYDKSF PISHVRFWVL QIIFVSVPTL LYLAHVFYVM RKEEKLNKKE EELKVAQTDG
   121  VNVDMHLKQI EIKKFKYGIE EHGKVKMRGG LLRTYIISIL FKSIFEVAFL LIQWYIYGFS
   181  LSAVYTCKRD PCPHQVDCFL SRPTEKTIFI IFMLVVSLVS LALNIIELFY VFFKGVKDRV
   241  KGKSDPYHAT SGALSPAKDC GSQKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN
   301  YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNSKKLAAG HELQPLAIVD
   361  QRPSSRASSR ASSRPRPDDL EI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GJA1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

4

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

366 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GJA1.

Disease | AllUniProt

Conditions GJA1 is implicated in, by any mechanism.

• Oculodentodigital dysplasia (ODDD) MIM:164200
• Oculodentodigital dysplasia, autosomal recessive (ODDD-AR) MIM:257850
• Syndactyly 3 (SDTY3) MIM:186100
• Hypoplastic left heart syndrome 1 (HLHS1) MIM:241550
• Hallermann-Streiff syndrome (HSS) MIM:234100
• Craniometaphyseal dysplasia, autosomal recessive (CMDR) MIM:218400
• Erythrokeratodermia variabilis et progressiva 3 (EKVP3) MIM:617525
• Palmoplantar keratoderma and congenital alopecia 1 (PPKCA1) MIM:104100

Disease | GeneticClinVar

60 pathogenic / likely-pathogenic of 368 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Oculodentodigital dysplasia, autosomal recessive
• Oculodentodigital dysplasia
• GJA1-related disorder
• Inborn genetic diseases
• Atrioventricular septal defect and common atrioventricular junction

ReferencesPubMed · IEDB

Publications for GJA1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.62

gnomAD pLI

0.16

gnomAD missense Z

1.28

DepMap mean gene effect

-0.17

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• atrial cardiac muscle cell action potential
• bone development
• bone remodeling
• cardiac conduction system development
• cell communication by electrical coupling
• cell communication by electrical coupling involved in cardiac conduction
• cell-cell signaling
• cellular response to amyloid-beta
• establishment of mitotic spindle orientation
• export across plasma membrane
• gap junction assembly
• glutamate secretion
• heart development
• intracellular protein localization
• maintenance of blood-brain barrier
• monoatomic ion transmembrane transport
• negative regulation of cell growth
• negative regulation of gonadotropin secretion
• negative regulation of trophoblast cell migration
• positive regulation of canonical NF-kappaB signal transduction
• positive regulation of cold-induced thermogenesis
• positive regulation of gene expression
• positive regulation of morphogenesis of an epithelium
• positive regulation of stem cell proliferation
• positive regulation of vascular associated smooth muscle cell proliferation
• signal transduction
• spermatogenesis
• xenobiotic transport
• microtubule-based transport
• positive regulation of mesodermal cell differentiation

Molecular functions

• alpha-tubulin binding
• beta-catenin binding
• efflux transmembrane transporter activity
• gap junction channel activity
• gap junction channel activity involved in cardiac conduction electrical coupling
• gap junction channel activity involved in cell communication by electrical coupling
• gap junction hemi-channel activity
• glutathione transmembrane transporter activity
• monoatomic ion transmembrane transporter activity
• tubulin binding

Cellular components

• apical plasma membrane
• cell junction
• cell-cell contact zone
• connexin complex
• cytoplasm
• endoplasmic reticulum membrane
• focal adhesion
• gap junction
• Golgi apparatus
• Golgi membrane
• Golgi-associated vesicle membrane
• intercalated disc
• membrane raft
• mitochondrion
• nucleoplasm
• nucleus
• plasma membrane
• tight junction

Protein domainsUniProt · Pfam · InterPro

• Connexin
• Connexin, N-terminal
• Connexin, conserved site
• Connexin, cysteine-rich domain
• Connexin, C-terminal
• Connexin, N-terminal domain superfamily
• Connexin
• Gap junction alpha-1 protein (Cx43)
• Gap junction alpha-1 protein (Cx43), C-terminal
• Gap junction alpha-1 protein (Cx43), alpha-helix domain superfamily
• Gap junction alpha-1 protein (Cx43)

KeywordsUniProt

• Acetylation
• Cataract
• Cell junction
• Cell membrane
• Disulfide bond
• Endoplasmic reticulum
• Gap junction
• Hypotrichosis
• Immunity
• Innate immunity
• Isopeptide bond
• Membrane
• Palmoplantar keratoderma
• Phosphoprotein
• S-nitrosylation
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of GJA1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CNST
• CSNK1D
• NOV
• PKP2
• SGSM3
• TMEM65
• AKAP8
• RIC1
• TJP1