Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

ZIC2

Reviewed September 2010

What is the official name of the ZIC2 gene?

The official name of this gene is “Zic family member 2.”

ZIC2 is the gene's official symbol. The ZIC2 gene is also known by other names, listed below.

What is the normal function of the ZIC2 gene?

The ZIC2 gene provides instructions for making a protein that plays an important role in the development of the front part of the brain (forebrain). This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of certain genes. The ZIC2 protein regulates genes involved in both early and late stages of forebrain development.

How are changes in the ZIC2 gene related to health conditions?

nonsyndromic holoprosencephaly - caused by mutations in the ZIC2 gene

More than 80 mutations in the ZIC2 gene have been found to cause nonsyndromic holoprosencephaly. This condition occurs when the brain fails to divide into two halves (hemispheres) during early development. ZIC2 gene mutations are the second most common cause of nonsyndromic holoprosencephaly. The facial features of individuals with ZIC2 gene mutations are different from those with nonsyndromic holoprosencephaly caused by mutations in other genes. These distinctive facial features include a narrowing of the head at the temples, outside corners of the eyes that point upward (upslanting palpebral fissures), large ears, a short nose with upturned nostrils, and a broad and deep space between the nose and mouth (philtrum). It is unclear how mutations in the ZIC2 gene lead to these facial features.

ZIC2 gene mutations that cause nonsyndromic holoprosencephaly reduce or eliminate the activity of the ZIC2 protein. Without enough functional ZIC2 protein, the genes involved in normal forebrain development are not properly controlled. As a result, the brain does not separate into two hemispheres. The signs and symptoms of nonsyndromic holoprosencephaly are caused by abnormal development of the brain and face.

Where is the ZIC2 gene located?

Cytogenetic Location: 13q32

Molecular Location on chromosome 13: base pairs 99,981,771 to 99,986,764

The ZIC2 gene is located on the long (q) arm of chromosome 13 at position 32.

The ZIC2 gene is located on the long (q) arm of chromosome 13 at position 32.

More precisely, the ZIC2 gene is located from base pair 99,981,771 to base pair 99,986,764 on chromosome 13.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about ZIC2?

You and your healthcare professional may find the following resources about ZIC2 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 ZIC2 gene or gene products?

  • HPE5
  • ZIC2_HUMAN
  • Zic family member 2 (odd-paired Drosophila homolog)
  • Zic family member 2 (odd-paired homolog, Drosophila)
  • Zinc finger protein of the cerebellum 2
  • zinc finger protein ZIC 2

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding ZIC2?

cerebellum ; DNA ; gene ; holoprosencephaly ; philtrum ; protein ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Brown LY, Odent S, David V, Blayau M, Dubourg C, Apacik C, Delgado MA, Hall BD, Reynolds JF, Sommer A, Wieczorek D, Brown SA, Muenke M. Holoprosencephaly due to mutations in ZIC2: alanine tract expansion mutations may be caused by parental somatic recombination. Hum Mol Genet. 2001 Apr 1;10(8):791-6. (http://www.ncbi.nlm.nih.gov/pubmed/11285244?dopt=Abstract)
  • Brown SA, Warburton D, Brown LY, Yu CY, Roeder ER, Stengel-Rutkowski S, Hennekam RC, Muenke M. Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired. Nat Genet. 1998 Oct;20(2):180-3. (http://www.ncbi.nlm.nih.gov/pubmed/9771712?dopt=Abstract)
  • Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V. Holoprosencephaly. Orphanet J Rare Dis. 2007 Feb 2;2:8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17274816?dopt=Abstract)
  • Gene Review: Holoprosencephaly Overview (http://www.ncbi.nlm.nih.gov/books/NBK1530)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7546)
  • Roessler E, Lacbawan F, Dubourg C, Paulussen A, Herbergs J, Hehr U, Bendavid C, Zhou N, Ouspenskaia M, Bale S, Odent S, David V, Muenke M. The full spectrum of holoprosencephaly-associated mutations within the ZIC2 gene in humans predicts loss-of-function as the predominant disease mechanism. Hum Mutat. 2009 Apr;30(4):E541-54. doi: 10.1002/humu.20982. (http://www.ncbi.nlm.nih.gov/pubmed/19177455?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20104595?dopt=Abstract)
  • Solomon BD, Lacbawan F, Mercier S, Clegg NJ, Delgado MR, Rosenbaum K, Dubourg C, David V, Olney AH, Wehner LE, Hehr U, Bale S, Paulussen A, Smeets HJ, Hardisty E, Tylki-Szymanska A, Pronicka E, Clemens M, McPherson E, Hennekam RC, Hahn J, Stashinko E, Levey E, Wieczorek D, Roeder E, Schell-Apacik CC, Booth CW, Thomas RL, Kenwrick S, Cummings DA, Bous SM, Keaton A, Balog JZ, Hadley D, Zhou N, Long R, Vélez JI, Pineda-Alvarez DE, Odent S, Roessler E, Muenke M. Mutations in ZIC2 in human holoprosencephaly: description of a novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals. J Med Genet. 2010 Aug;47(8):513-24. doi: 10.1136/jmg.2009.073049. Epub 2009 Dec 2. (http://www.ncbi.nlm.nih.gov/pubmed/19955556?dopt=Abstract)
  • Solomon BD, Mercier S, Vélez 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20104608?dopt=Abstract)
  • Warr N, Powles-Glover N, Chappell A, Robson J, Norris D, Arkell RM. Zic2-associated holoprosencephaly is caused by a transient defect in the organizer region during gastrulation. Hum Mol Genet. 2008 Oct 1;17(19):2986-96. doi: 10.1093/hmg/ddn197. Epub 2008 Jul 9. (http://www.ncbi.nlm.nih.gov/pubmed/18617531?dopt=Abstract)
  • OMIM: ZINC FINGER PROTEIN OF CEREBELLUM 2 (http://omim.org/entry/603073)

 

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? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2010
Published: November 24, 2014