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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed January 2014

What is the official name of the GJB4 gene?

The official name of this gene is “gap junction protein beta 4.”

GJB4 is the gene's official symbol. The GJB4 gene is also known by other names, listed below.

What is the normal function of the GJB4 gene?

The GJB4 gene provides instructions for making a protein called gap junction beta 4, more commonly known as connexin 30.3. This protein is part of the connexin family, a group of proteins that form channels called gap junctions on the surface of cells. Gap junctions open and close to regulate the flow of nutrients, charged atoms (ions), and other signaling molecules from one cell to another. They are essential for direct communication between neighboring cells.

Connexin 30.3 is found in several different tissues, including the outermost layer of the skin (the epidermis). This protein appears to play a role in the growth and maturation of epidermal cells.

Does the GJB4 gene share characteristics with other genes?

The GJB4 gene belongs to a family of genes called GJ (gap junction proteins (connexins)).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? ( in the Handbook.

How are changes in the GJB4 gene related to health conditions?

erythrokeratodermia variabilis et progressiva - caused by mutations in the GJB4 gene

At least seven GJB4 gene mutations have been identified in people with erythrokeratodermia variabilis et progressiva (EKVP), a skin disorder characterized by areas of hyperkeratosis, which is abnormally thickened skin, and temporarily reddened patches called erythematous areas. Each of these mutations changes a single protein building block (amino acid) used to make connexin 30.3. Studies suggest that the abnormal protein can build up in a cell structure called the endoplasmic reticulum (ER), triggering a harmful process known as ER stress. Researchers suspect that ER stress damages and leads to the premature death of cells in the epidermis. This cell death leads to skin inflammation, which appears to underlie the development of erythematous areas. The mechanism by which epidermal damage and cell death contributes to hyperkeratosis is poorly understood.

Where is the GJB4 gene located?

Cytogenetic Location: 1p34.3

Molecular Location on chromosome 1: base pairs 34,759,741 to 34,763,724

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

The GJB4 gene is located on the short (p) arm of chromosome 1 at position 34.3.

The GJB4 gene is located on the short (p) arm of chromosome 1 at position 34.3.

More precisely, the GJB4 gene is located from base pair 34,759,741 to base pair 34,763,724 on chromosome 1.

See How do geneticists indicate the location of a gene? ( in the Handbook.

Where can I find additional information about GJB4?

You and your healthcare professional may find the following resources about GJB4 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the GJB4 gene or gene products?

  • connexin 30.3
  • connexin-30.3
  • CX30.3
  • EKV
  • gap junction beta-4 protein
  • gap junction protein, beta 4, 30.3kDa

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding GJB4?

amino acid ; cell ; connexin ; endoplasmic reticulum ; epidermis ; ER ; gap junctions ; gene ; inflammation ; ions ; oxygen ; protein ; reactive oxygen species ; stress

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Macari F, Landau M, Cousin P, Mevorah B, Brenner S, Panizzon R, Schorderet DF, Hohl D, Huber M. Mutation in the gene for connexin 30.3 in a family with erythrokeratodermia variabilis. Am J Hum Genet. 2000 Nov;67(5):1296-301. Epub 2000 Oct 3. (
  • NCBI Gene (
  • Richard G, Brown N, Rouan F, Van der Schroeff JG, Bijlsma E, Eichenfield LF, Sybert VP, Greer KE, Hogan P, Campanelli C, Compton JG, Bale SJ, DiGiovanna JJ, Uitto J. Genetic heterogeneity in erythrokeratodermia variabilis: novel mutations in the connexin gene GJB4 (Cx30.3) and genotype-phenotype correlations. J Invest Dermatol. 2003 Apr;120(4):601-9. (
  • Scott CA, O'Toole EA, Mohungoo MJ, Messenger A, Kelsell DP. Novel and recurrent connexin 30.3 and connexin 31 mutations associated with erythrokeratoderma variabilis. Clin Exp Dermatol. 2011 Jan;36(1):88-90. (
  • van Steensel MA, Oranje AP, van der Schroeff JG, Wagner A, van Geel M. The missense mutation G12D in connexin30.3 can cause both erythrokeratodermia variabilis of Mendes da Costa and progressive symmetric erythrokeratodermia of Gottron. Am J Med Genet A. 2009 Feb 15;149A(4):657-61. doi: 10.1002/ajmg.a.32744. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: January 2014
Published: February 8, 2016