The SHH gene provides instructions for making a protein called Sonic Hedgehog. This protein functions as a chemical signal that is essential for embryonic development. Sonic Hedgehog plays a role in cell growth, cell specialization, and the normal shaping (patterning) of the body. This protein is important for development of the brain and spinal cord (central nervous system), eyes, limbs, and many other parts of the body.
Sonic Hedgehog is necessary for the development of the front part of the brain (forebrain). This signaling protein helps establish the line that separates the right and left sides of the forebrain (the midline). Specifically, Sonic Hedgehog establishes the midline for the underside (ventral surface) of the forebrain. Sonic Hedgehog and other signaling proteins are needed to form the right and left halves (hemispheres) of the brain.
Sonic Hedgehog also has an important role in the formation of the eyes. During early development, the cells that develop into the eyes form a single structure called the eye field. This structure is located in the center of the developing face. Sonic hedgehog signaling causes the eye field to separate into two distinct eyes.
Health Conditions Related to Genetic Changes
More than 100 mutations in the SHH gene have been found to cause nonsyndromic holoprosencephaly. This condition occurs when the brain fails to divide into two hemispheres during early development. SHH gene mutations are the most common cause of nonsyndromic holoprosencephaly. These mutations reduce or eliminate the activity of Sonic Hedgehog. Without the correct activity of this protein, the eyes will not form normally and the brain does not separate into two hemispheres. The development of other parts of the face is affected if the eyes do not move to their proper position. The signs and symptoms of nonsyndromic holoprosencephaly are caused by abnormal development of the brain and face.More About This Health Condition
MedlinePlus Genetics provides information about ColobomaMore About This Health Condition
MedlinePlus Genetics provides information about MicrophthalmiaMore About This Health Condition
Other Names for This Gene
- sonic hedgehog homolog (Drosophila)
- sonic hedgehog protein
- sonic hedgehog protein preproprotein
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V. Holoprosencephaly. Orphanet J Rare Dis. 2007 Feb 2;2:8. doi: 10.1186/1750-1172-2-8. Citation on PubMed or Free article on PubMed Central
- Monuki ES. The morphogen signaling network in forebrain development and holoprosencephaly. J Neuropathol Exp Neurol. 2007 Jul;66(7):566-75. doi: 10.1097/nen.0b013e3180986e1b. Citation on PubMed
- Nanni L, Ming JE, Bocian M, Steinhaus K, Bianchi DW, Die-Smulders C, Giannotti A, Imaizumi K, Jones KL, Campo MD, Martin RA, Meinecke P, Pierpont ME, Robin NH, Young ID, Roessler E, Muenke M. The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. Hum Mol Genet. 1999 Dec;8(13):2479-88. doi: 10.1093/hmg/8.13.2479. Citation on PubMed
- Nanni L, Ming JE, Du Y, Hall RK, Aldred M, Bankier A, Muenke M. SHH mutation is associated with solitary median maxillary central incisor: a study of 13 patients and review of the literature. Am J Med Genet. 2001 Jul 22;102(1):1-10. doi: 10.1002/1096-8628(20010722)102:13.0.co;2-u. Citation on PubMed
- Roessler E, El-Jaick KB, Dubourg C, Velez JI, Solomon BD, Pineda-Alvarez DE, Lacbawan F, Zhou N, Ouspenskaia M, Paulussen A, Smeets HJ, Hehr U, Bendavid C, Bale S, Odent S, David V, Muenke M. The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis. Hum Mutat. 2009 Oct;30(10):E921-35. doi: 10.1002/humu.21090. Citation on PubMed or Free article on PubMed Central
- Roessler E, Muenke M. The molecular genetics of holoprosencephaly. Am J Med Genet C Semin Med Genet. 2010 Feb 15;154C(1):52-61. doi: 10.1002/ajmg.c.30236. Citation on PubMed or Free article on PubMed Central
- Solomon BD, Mercier S, Velez JI, Pineda-Alvarez DE, Wyllie A, Zhou N, Dubourg C, David V, Odent S, Roessler E, Muenke M. Analysis of genotype-phenotype correlations in human holoprosencephaly. Am J Med Genet C Semin Med Genet. 2010 Feb 15;154C(1):133-41. doi: 10.1002/ajmg.c.30240. Citation on PubMed or Free article on PubMed Central
- Tekendo-Ngongang C, Muenke M, Kruszka P. Holoprosencephaly Overview. 2000 Dec 27 [updated 2020 Mar 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK1530/ Citation on PubMed