GLI3

Chr 7AD

GLI family zinc finger 3

Also known as: ACLS, GCPS, GLI3-190, GLI3FL, PAP-A, PAPA, PAPA1, PAPB

NCBI Gene: 2737 ENSG00000106571 UniProt: P10071 OMIM: 165240

This gene encodes GLI3, a zinc finger transcription factor that acts as both an activator and repressor in the sonic hedgehog signaling pathway and is essential for proper limb development and digit formation. Mutations cause autosomal dominant conditions including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, and various forms of polydactyly, all characterized by limb malformations and often craniofacial abnormalities. The gene is highly constrained against loss-of-function variants in the general population, reflecting its critical role in development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein which belongs to the C2H2-type zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding transcription factors and are mediators of Sonic hedgehog (Shh) signaling. The protein encoded by this gene localizes in the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis. Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Greig cephalopolysyndactyly syndromeMIM #175700

Pallister-Hall syndromeMIM #146510

Polydactyly, postaxial, types A1 and BMIM #174200

Polydactyly, preaxial, type IVMIM #174700

UniProtGreig cephalo-poly-syndactyly syndrome

Clinical highlights

Gene-disease validity (ClinGen)

Greig cephalopolysyndactyly syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.20

LOEUF· LoF intol.

Multiple*

Mechanism· G2P

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