GLIS3

Protein identityUniProt · HPA

UniProt accession

Q8NEA6

Gene

GLIS3

Ensembl

ENSG00000107249

Chromosome

9

Canonical length

775 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm,Golgi apparatus,Primary cilium

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

775 residues, UniProt reviewed canonical sequence.

>Q8NEA6|GLIS3
     1  MMVQRLGLIS PPASQVSTAC NQISPSLQRA MNAANLNIPP SDTRSLISRE SLASTTLSLT
    61  ESQSASSMKQ EWSQGYRALP SLSNHGSQNG LDLGDLLSLP PGTSMSSNSV SNSLPSYLFG
   121  TESSHSPYPS PRHSSTRSHS ARSKKRALSL SPLSDGIGID FNTIIRTSPT SLVAYINGSR
   181  ASPANLSPQP EVYGHFLGVR GSCIPQPRPV PGSQKGVLVA PGGLALPAYG EDGALEHERM
   241  QQLEHGGLQP GLVNHMVVQH GLPGPDSQSA GLFKTERLEE FPGSTVDLPP APPLPPLPPP
   301  PGPPPPYHAH AHLHHPELGP HAQQLALPQA TLDDDGEMDG IGGKHCCRWI DCSALYDQQE
   361  ELVRHIEKVH IDQRKGEDFT CFWAGCPRRY KPFNARYKLL IHMRVHSGEK PNKCTFEGCE
   421  KAFSRLENLK IHLRSHTGEK PYLCQHPGCQ KAFSNSSDRA KHQRTHLDTK PYACQIPGCT
   481  KRYTDPSSLR KHVKAHSSKE QQARKKLRSS TELHPDLLTD CLTVQSLQPA TSPRDAAAEG
   541  TVGRSPGPGP DLYSAPIFSS NYSSRSGTAA GAVPPPHPVS HPSPGHNVQG SPHNPSSQLP
   601  PLTAVDAGAE RFAPSAPSPH HISPRRVPAP SSILQRTQPP YTQQPSGSHL KSYQPETNSS
   661  FQPNGIHVHG FYGQLQKFCP PHYPDSQRIV PPVSSCSVVP SFEDCLVPTS MGQASFDVFH
   721  RAFSTHSGIT VYDLPSSSSS LFGESLRSGA EDATFLQIST VDRCPSQLSS VYTEG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GLIS3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.64

Highest tissue expression

14 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GLIS3.

Disease | AllUniProt

Conditions GLIS3 is implicated in, by any mechanism.

• Diabetes mellitus, neonatal, with congenital hypothyroidism (NDH) MIM:610199

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 794 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neonatal diabetes mellitus with congenital hypothyroidism
• GLIS3-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.74

gnomAD pLI

0

gnomAD missense Z

-3.14

DepMap mean gene effect

0.12

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• negative regulation of transcription by RNA polymerase II
• positive regulation of transcription by RNA polymerase II
• regulation of transcription by RNA polymerase II
• transcription by RNA polymerase II

Molecular functions

• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity, RNA polymerase II-specific
• DNA-binding transcription repressor activity, RNA polymerase II-specific
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• zinc ion binding

Cellular components

• nucleus

Protein domainsUniProt · Pfam · InterPro

• Zinc finger C2H2-type
• Zinc finger C2H2 superfamily
• C2H2-type zinc-finger protein GLI-like
• ZIC1-5/GLI1-3like, C2H2 zinc finger
• Zinc finger, C2H2 type
• C2H2 zinc finger

KeywordsUniProt

• Activator
• Congenital hypothyroidism
• Diabetes mellitus
• DNA-binding
• Metal-binding
• Nucleus
• Repeat
• Repressor
• Transcription
• Transcription regulation
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of GLIS3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SUFU