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GLI3 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

GLI3 gene

The GLI3 gene acts as a transcription factor that regulates gene expression, playing a vital role in the early development and patterning of tissues and organs.

Overview

The GLI3 gene belongs to a family of genes involved in the early development of many tissues and organs. Proteins produced by this gene act as transcription factors, attaching to specific regions of DNA to control whether other genes are turned on or off.

The GLI3 protein functions within the Sonic Hedgehog signaling pathway, which is essential for cell growth, specialization, and the patterning of structures such as the brain and limbs. Depending on the signals received, GLI3 can either activate or repress target genes.

Health Conditions Related to Genetic Changes

Acrocallosal syndrome

Mutations in the GLI3 gene can cause acrocallosal syndrome, a rare condition characterized by:

  • Brain abnormalities
  • Extra fingers and toes (polydactyly)
  • Distinctive facial features, including widely spaced eyes (hypertelorism) and a prominent forehead

Greig cephalopolysyndactyly syndrome

This condition is caused by genetic changes that prevent one copy of the GLI3 gene from producing functional protein, resulting in a reduced amount of GLI3 available during development. Features include:

  • Polydactyly
  • Hypertelorism
  • Broad forehead
  • Unusually large head (macrocephaly)

Pallister-Hall syndrome

Mutations near the middle of the gene often create a premature stop signal, leading to the production of an unusually short version of the GLI3 protein. This short protein can only repress target genes. Major features include:

  • Polydactyly
  • Hypothalamic hamartoma (an abnormal growth in the brain)
  • Bifid epiglottis (a malformation of the airway)

Other disorders

GLI3 mutations can also cause isolated or nonsyndromic polydactyly, where extra digits occur without other systemic features. These include:

  • Postaxial polydactyly type A (PAP-A) and type A/B (PAP-A/B): Extra digits next to the little finger or small toe.
  • Preaxial polydactyly type IV (PPD-IV): Extra digits next to the thumb or big toe, often accompanied by fused skin (cutaneous syndactyly).

Other Names for This Gene

  • ACLS
  • GCPS
  • GLI-Kruppel family member GLI3 (Greig cephalopolysyndactyly syndrome)
  • GLI3_HUMAN
  • oncogene GLI3
  • PAP-A
  • PAPA
  • PAPA1
  • PAPB
  • PHS
  • PPDIV
  • zinc finger protein GLI3

Frequently Asked Questions

The most urgent signs are new‑onset or worsening seizures, especially if they become prolonged (status epilepticus) or are accompanied by loss of consciousness, breathing difficulties, or injury. If a seizure lasts more than 5 minutes, call emergency services (911) and administer any prescribed rescue medication (e.g., rectal diazepam or intranasal midazolam) while waiting for help. Regular follow‑up with a pediatric neurologist is essential to adjust antiepileptic therapy and consider surgical options for the hamartoma if seizures are refractory.
Yes. Orthopedic surgeons often recommend early removal of supernumerary digits, ideally before the child begins walking (typically between 6 months and 2 years of age) to minimize functional impairment and improve cosmetic outcome. Pre‑operative imaging (X‑ray or MRI) helps determine bone and tendon involvement. Post‑operative physical therapy may be needed to ensure normal hand or foot function.
GLI3-related disorders are typically inherited in an autosomal‑dominant pattern, meaning a single altered copy of the gene can cause disease. Genetic testing usually involves sequencing the GLI3 coding regions and copy‑number analysis to detect deletions or duplications. A positive result indicates that you carry a pathogenic variant; each child has a 50 % chance of inheriting the same variant. Genetic counseling can discuss options such as prenatal diagnosis (chorionic villus sampling or amniocentesis) or pre‑implantation genetic testing if you are considering assisted reproduction.
Prenatal ultrasound may reveal limb anomalies such as extra digits (polydactyly), brain structural abnormalities, or an enlarged head (macrocephaly) that raise suspicion for a GLI3‑related condition. If a known familial GLI3 variant exists, targeted molecular testing via amniocentesis or chorionic villus sampling can confirm the diagnosis. While there is no in‑utero therapy to correct the genetic defect, early diagnosis allows for coordinated perinatal planning, including neonatal specialist involvement and parental counseling.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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