GLIS3

Chr 9AR

GLIS family zinc finger 3

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.741 OMIM phenotype
Clinical SummaryGLIS3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.000
Z-score 2.81
OE 0.50 (0.340.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-3.14Z-score
OE missense 1.37 (1.291.46)
772 obs / 562.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.50 (0.340.74)
00.351.4
Missense OE1.37 (1.291.46)
00.61.4
Synonymous OE1.38
01.21.6
LoF obs/exp: 18 / 36.3Missense obs/exp: 772 / 562.7Syn Z: -4.73
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGLIS3-related diabetes mellitus neonatal with congenital hypothyroidismLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7130th %ile
GOF
0.3887th %ile
LOF
0.56top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GLIS3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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