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

BHLH gene family

Reviewed March 2011

What are the bHLH genes?

Genes in the bHLH family provide instructions for transcription factors known as basic helix-loop-helix proteins. Transcription factors are proteins that attach (bind) to specific regions of DNA and help control the activity of particular genes. The basic helix-loop-helix proteins are critical in controlling (regulating) many pathways during development.

Basic helix-loop-helix transcription factors contain a region in the protein called a basic helix-loop-helix domain. This domain allows the protein to bind to another protein (dimerize) and then to DNA. When the proteins bind to DNA, they control the activity of particular genes. Some basic helix-loop-helix proteins can turn on (activate) certain genes and others turn off (repress) certain genes.

Basic helix-loop-helix proteins play a role in many cellular and developmental processes, including cell growth and division and development of body systems in the embryo. Mutations in bHLH genes can have a number of effects, such as abnormal development of the heart, mental delays, cancer, and bone abnormalities. Mutations in the bHLH gene MESP2 result in malformation of the spine and ribs seen in spondylothoracic dysostosis and spondylocostal dysostosis.

Which genes are included in the bHLH gene family?

The HUGO Gene Nomenclature Committee (HGNC) provides an index of gene families ( and their member genes.

Genetics Home Reference summarizes the normal function and health implications of these members of the bHLH gene family: EPAS1, HES7, MESP2, MITF, MYCN, TCF4, and TWIST1.

What conditions are related to genes in the bHLH gene family?

Genetics Home Reference includes these conditions related to genes in the bHLH gene family:

  • familial erythrocytosis
  • Feingold syndrome
  • Fuchs endothelial dystrophy
  • neuroblastoma
  • Pitt-Hopkins syndrome
  • Saethre-Chotzen syndrome
  • spondylocostal dysostosis
  • spondylothoracic dysostosis
  • Tietz syndrome
  • Waardenburg syndrome

Where can I find additional information about the bHLH gene family?

You may find the following resources about the bHLH gene family helpful.

  • Molecular Cell Biology (4th Edition, 2000): Myogenic Proteins Are Transcription Factors Containing a Common bHLH Domain (
  • Molecular Cell Biology (4th Edition, 2000): Progressive Restriction of Neural Potential Requires Inhibitory HLH Proteins and Local Cell-Cell Interactions (

What glossary definitions help with understanding the bHLH gene family?

cancer ; cell ; DNA ; domain ; embryo ; gene ; malformation ; mesoderm ; oncogene ; posterior ; protein ; transcription ; transcription factor

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


These sources were used to develop the Genetics Home Reference summary for the bHLH gene family.

  • Murre C, Bain G, van Dijk MA, Engel I, Furnari BA, Massari ME, Matthews JR, Quong MW, Rivera RR, Stuiver MH. Structure and function of helix-loop-helix proteins. Biochim Biophys Acta. 1994 Jun 21;1218(2):129-35. Review. (
  • Massari ME, Murre C. Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol. 2000 Jan;20(2):429-40. Review. (
  • Ledent V, Vervoort M. The basic helix-loop-helix protein family: comparative genomics and phylogenetic analysis. Genome Res. 2001 May;11(5):754-70. (


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: March 2011
Published: February 1, 2016