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


Reviewed March 2006

What is the official name of the GLI3 gene?

The official name of this gene is “GLI family zinc finger 3.”

GLI3 is the gene's official symbol. The GLI3 gene is also known by other names, listed below.

What is the normal function of the GLI3 gene?

The GLI3 gene belongs to a family of genes that are involved in the normal shaping (patterning) of many tissues and organs during embryonic development. To carry out this role, proteins made by genes in the GLI family attach to specific regions of DNA and help control whether particular genes are turned on or off (gene expression). GLI proteins are called transcription factors on the basis of this action.

Proteins in the GLI family function in the same molecular pathway as a protein called Sonic Hedgehog. This pathway is essential for early development. It plays a role in cell growth, cell specialization, and the patterning of structures such as the brain and limbs. Depending on signals from Sonic Hedgehog, the GLI3 protein can either turn on (activate) or turn off (repress) other genes. Researchers are working to identify the genes targeted by the GLI3 protein during development.

How are changes in the GLI3 gene related to health conditions?

Greig cephalopolysyndactyly syndrome - caused by mutations in the GLI3 gene

Several types of mutations in the GLI3 gene have been identified in people with Greig cephalopolysyndactyly syndrome. These genetic changes include insertions or deletions of a small amount of DNA and changes in single DNA building blocks (base pairs) in critical regions of the gene. In other cases, this condition is caused by chromosomal abnormalities involving the region of chromosome 7 that contains the GLI3 gene. The genetic changes that cause Greig cephalopolysyndactyly syndrome prevent one copy of the gene in each cell from producing any functional GLI3 protein. As a result, only half the normal amount of this protein is available to control the expression of target genes during embryonic development. It remains unclear how a reduced amount of the GLI3 protein disrupts development of the limbs, head, and face and causes the specific features of Greig cephalopolysyndactyly syndrome.

Pallister-Hall syndrome - caused by mutations in the GLI3 gene

Most of the mutations responsible for Pallister-Hall syndrome occur near the middle of the GLI3 gene. These genetic changes typically create a premature stop signal in the instructions for making the GLI3 protein. As a result, cells produce an unusually short version of the protein. Unlike the full-length GLI3 protein, which can turn target genes on or off, the short protein can only turn off (repress) the expression of target genes. Although this defect clearly disrupts aspects of embryonic development, it is not known how the altered function of the GLI3 protein leads to the varied signs and symptoms of Pallister-Hall syndrome.

other disorders - caused by mutations in the GLI3 gene

Mutations in the GLI3 gene have been found in people with several forms of polydactyly (the presence of extra fingers and/or toes). These cases are described as isolated or nonsyndromic because the polydactyly occurs without other signs and symptoms, such as brain abnormalities or widely spaced eyes. GLI3 mutations can cause two types of polydactyly that are characterized by an extra digit next to the little finger or the small toe. These conditions are called postaxial polydactyly type A (PAP-A) and type A/B (PAP-A/B). Another form of polydactyly, preaxial polydactyly type IV (PPD-IV), can also result from mutations in the GLI3 gene. People with this condition have extra digits next to the thumb or big toe (hallux) and fused skin between some fingers and toes (cutaneous syndactyly). PPD-IV also can include extra digits in other positions on the hands or feet. The pattern of polydactyly seen with PPD-IV is similar to that of Greig cephalopolysyndactyly syndrome, and some researchers suggest that PPD-IV may be a very mild form of that syndrome.

Where is the GLI3 gene located?

Cytogenetic Location: 7p13

Molecular Location on chromosome 7: base pairs 41,960,949 to 42,264,112

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

The GLI3 gene is located on the short (p) arm of chromosome 7 at position 13.

The GLI3 gene is located on the short (p) arm of chromosome 7 at position 13.

More precisely, the GLI3 gene is located from base pair 41,960,949 to base pair 42,264,112 on chromosome 7.

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

Where can I find additional information about GLI3?

You and your healthcare professional may find the following resources about GLI3 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 GLI3 gene or gene products?

  • ACLS
  • GCPS
  • GLI-Kruppel family member GLI3 (Greig cephalopolysyndactyly syndrome)
  • oncogene GLI3
  • PAPA
  • PAP-A
  • PAPA1
  • PAPB
  • PHS
  • zinc finger protein GLI3

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

What glossary definitions help with understanding GLI3?

big toe ; cell ; chromosome ; cutaneous ; DNA ; embryonic ; gene ; gene expression ; hallux ; oncogene ; polydactyly ; protein ; syndactyly ; syndrome ; transcription

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


  • Biesecker LG, Johnston J. Syndromic and non-syndromic GLI3 phenotypes. Clin Genet. 2005 Sep;68(3):284; author reply 285. (
  • Fujioka H, Ariga T, Horiuchi K, Otsu M, Igawa H, Kawashima K, Yamamoto Y, Sugihara T, Sakiyama Y. Molecular analysis of non-syndromic preaxial polydactyly: preaxial polydactyly type-IV and preaxial polydactyly type-I. Clin Genet. 2005 May;67(5):429-33. (
  • Gene Review: Greig Cephalopolysyndactyly Syndrome (
  • Gene Review: Pallister-Hall Syndrome (
  • Hu MC, Mo R, Bhella S, Wilson CW, Chuang PT, Hui CC, Rosenblum ND. GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis. Development. 2006 Feb;133(3):569-78. Epub 2006 Jan 5. (
  • Johnston JJ, Olivos-Glander I, Killoran C, Elson E, Turner JT, Peters KF, Abbott MH, Aughton DJ, Aylsworth AS, Bamshad MJ, Booth C, Curry CJ, David A, Dinulos MB, Flannery DB, Fox MA, Graham JM, Grange DK, Guttmacher AE, Hannibal MC, Henn W, Hennekam RC, Holmes LB, Hoyme HE, Leppig KA, Lin AE, Macleod P, Manchester DK, Marcelis C, Mazzanti L, McCann E, McDonald MT, Mendelsohn NJ, Moeschler JB, Moghaddam B, Neri G, Newbury-Ecob R, Pagon RA, Phillips JA, Sadler LS, Stoler JM, Tilstra D, Walsh Vockley CM, Zackai EH, Zadeh TM, Brueton L, Black GC, Biesecker LG. Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations. Am J Hum Genet. 2005 Apr;76(4):609-22. Epub 2005 Feb 28. (
  • Johnston JJ, Olivos-Glander I, Turner J, Aleck K, Bird LM, Mehta L, Schimke RN, Heilstedt H, Spence JE, Blancato J, Biesecker LG. Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome. Am J Med Genet A. 2003 Dec 15;123A(3):236-42. (
  • Kalff-Suske M, Wild A, Topp J, Wessling M, Jacobsen EM, Bornholdt D, Engel H, Heuer H, Aalfs CM, Ausems MG, Barone R, Herzog A, Heutink P, Homfray T, Gillessen-Kaesbach G, König R, Kunze J, Meinecke P, Müller D, Rizzo R, Strenge S, Superti-Furga A, Grzeschik KH. Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactyly syndrome. Hum Mol Genet. 1999 Sep;8(9):1769-77. (
  • Kang S, Graham JM Jr, Olney AH, Biesecker LG. GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Nat Genet. 1997 Mar;15(3):266-8. (
  • Kang S, Rosenberg M, Ko VD, Biesecker LG. Gene structure and allelic expression assay of the human GLI3 gene. Hum Genet. 1997 Dec;101(2):154-7. (
  • NCBI Gene (
  • Radhakrishna U, Bornholdt D, Scott HS, Patel UC, Rossier C, Engel H, Bottani A, Chandal D, Blouin JL, Solanki JV, Grzeschik KH, Antonarakis SE. The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant preaxial polydactyly type-IV and postaxial polydactyly type-A/B; No phenotype prediction from the position of GLI3 mutations. Am J Hum Genet. 1999 Sep;65(3):645-55. (
  • Shin SH, Kogerman P, Lindström E, Toftgárd R, Biesecker LG. GLI3 mutations in human disorders mimic Drosophila cubitus interruptus protein functions and localization. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2880-4. (
  • Villavicencio EH, Walterhouse DO, Iannaccone PM. The sonic hedgehog-patched-gli pathway in human development and disease. Am J Hum Genet. 2000 Nov;67(5):1047-54. Epub 2000 Sep 21. Review. (
  • Wild A, Kalff-Suske M, Vortkamp A, Bornholdt D, König R, Grzeschik KH. Point mutations in human GLI3 cause Greig syndrome. Hum Mol Genet. 1997 Oct;6(11):1979-84. (


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 2006
Published: February 8, 2016