GJA1

Chr 6

gap junction protein alpha 1

Also known as: AVSD3, CMDR, CX43, EKVP, EKVP3, GJAL, HLHS1, HSS

NCBI Gene: 2697 ENSG00000152661 UniProt: P17302

The encoded protein forms connexin 43, the major gap junction protein that creates intercellular channels allowing diffusion of small molecules between cells, particularly important for synchronized cardiac contraction and embryonic development. Mutations cause oculodentodigital dysplasia, craniometaphyseal dysplasia, erythrokeratodermia variabilis et progressiva, and syndactyly through both autosomal dominant and autosomal recessive inheritance patterns. Disease can result from multiple mechanisms including gain-of-function effects from specific mutations that disrupt normal gap junction function.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtOculodentodigital dysplasia

UniProtOculodentodigital dysplasia, autosomal recessive

UniProtSyndactyly 3

UniProtHypoplastic left heart syndrome 1

Clinical highlights

Gene-disease validity (ClinGen)

congenital heart disease · UDLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

129

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.62

LOEUF

Multiple*

Mechanism· G2P

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