GLIS2

Chr 16AR

GLIS family zinc finger 2

Also known as: NKL, NPHP7

NCBI Gene: 84662 ENSG00000126603 UniProt: Q9BZE0 OMIM: 608539

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear transcription factor with five C2H2-type zinc finger domains. The protein encoded by this gene is widely expressed at low levels in the neural tube and peripheral nervous system and likely promotes neuronal differentiation. It is abundantly expressed in the kidney and may have a role in the regulation of kidney morphogenesis. p120 regulates the expression level of this protein and induces the cleavage of this protein's C-terminal zinc finger domain. This protein also promotes the nuclear translocation of p120. Mutations in this gene cause nephronophthisis (NPHP), an autosomal recessive kidney disease characterized by tubular basement membrane disruption, interstitial lymphohistiocytic cell infiltration, and development of cysts at the corticomedullary border of the kidneys.[provided by RefSeq, Jan 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Nephronophthisis 7MIM #611498

Clinical highlights

Gene-disease validity (ClinGen)

nephronophthisis 7 · ARModerateconsider for supplementary testing

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

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.41

LOEUF

LOF

Mechanism· G2P

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GeneReview available — GLIS2