GLIS2

Chr 16AR

GLIS family zinc finger 2

Also known as: NKL, NPHP7

GLIS2 encodes a nuclear transcription factor with zinc finger domains that regulates gene expression in kidney morphogenesis and neuronal differentiation, particularly maintaining epithelial cell identity in renal tissues. Mutations cause nephronophthisis 7, an autosomal recessive kidney disease characterized by tubular basement membrane disruption, interstitial infiltration, and cyst development at the kidney's corticomedullary border. The gene is highly constrained against loss-of-function variants (pLI 0.86, LOEUF 0.42), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.411 OMIM phenotype
Clinical SummaryGLIS2
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Gene-Disease Validity (ClinGen)
nephronophthisis 7 · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.858
Z-score 3.14
OE 0.13 (0.050.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.79Z-score
OE missense 0.88 (0.800.97)
290 obs / 330.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.050.41)
00.351.4
Missense OE0.88 (0.800.97)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 2 / 15.2Missense obs/exp: 290 / 330.5Syn Z: -0.94
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongGLIS2-related nephronophthisisLOFAR

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

DN
0.4784th %ile
GOF
0.3986th %ile
LOF
0.78top 5%

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GLIS2 · 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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