GLI2

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The GLI2 gene codes for the 1586 amino acid zinc finger protein GLI2. This is a transcription regulator in the hedgehog (Hh) pathway and definitely functions as a transcriptional activator, although may have transcriptional repressor roles. It is permissive for normal embryonic development. As both hedgehog pathways and transforming growth factor beta signalling both converge to GLI2 expression in systemic sclerosis to promote fibrosis small molecule inhibitors are being developed[1]. It also promotes levels of parathyroid hormone-related peptide so is a therapeutic target to prevent bony invasion by squamous cell carcinomas[2]. However by analogy such inhibitors might affect pituitary function.

Mutations cause:

  • Holoprosencephaly 9 (HPE9, OMIM:610829)
    • The developing forebrain fails to correctly separate into right and left hemispheres. There is defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and holoprosencephaly-like midfacial hypoplasia.
  • Culler-Jones syndrome (CJS, OMIM:615849)
    • An autosomal dominant disorder with usually:
      • Hypothalamic hamartoma
      • hypopituitarism
      • Central or postaxial polydactyly, and syndactyly
      • Malformations are frequent in the viscera, e.g. anal atresia, bifid uvula, congenital heart malformations, pulmonary or renal dysplasia

References

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