GLIS3

Chr 9

GLIS family zinc finger 3

Also known as: NDH, ZNF515

NCBI Gene: 169792 ENSG00000107249 UniProt: Q8NEA6

GLIS3 encodes a zinc finger transcription factor that functions as both a transcriptional repressor and activator, specifically controlling the development of pancreatic beta cells, thyroid, eye, liver, and kidney. Mutations cause neonatal diabetes with congenital hypothyroidism, presenting in the newborn period with severe hyperglycemia and thyroid dysfunction. This condition follows autosomal recessive inheritance.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear protein with five C2H2-type zinc finger domains. This protein functions as both a repressor and activator of transcription and is specifically involved in the development of pancreatic beta cells, the thyroid, eye, liver and kidney. Mutations in this gene have been associated with neonatal diabetes and congenital hypothyroidism (NDH). Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only two have been determined. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDiabetes mellitus, neonatal, with congenital hypothyroidism

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.74

LOEUF

LOF

Mechanism· G2P

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GeneReview available — GLIS3