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<scp>GLI</scp> Proteins in Human Genetic Disease

2012· other· en· W1851359940 on OpenAlexaff
Olena Zhulyn, Hui Chi‐chung

Bibliographic record

VenueEncyclopedia of Life Sciences · 2012
Typeother
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHedgehog Signaling Pathway Studies
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsCiliumCiliogenesisGLI2BiologyGLI3PhenotypeGeneticsCiliopathiesHedgehog signaling pathwayTranscription factorHedgehogRepressorLoss functionCell biologyGene

Abstract

fetched live from OpenAlex

Abstract GLI1, GLI2 and GLI3 transcription factors are the key effectors of mammalian Hedgehog signalling. Mutations in these transcription factors are implicated in severe congenital malformations and malignancies in humans and in mice. Analysis of mouse models has revealed that the patterning and development of multiple organ systems is dependent on a tightly regulated balance of Gli activator and repressor activity. Consequently, mutations in the Hh pathway machinery that affect Gli function or processing result in phenotypes with a striking resemblance to GLI‐associated disorders. The primary cilium was identified as a critical component of Hh signalling due to the phenotypic overlap between Hh‐pathway mutants and mice with defects in ciliogenesis. Many mutations in genes regulating cilia structure and function have been identified in human ciliopathies. This new class of diseases shares significant phenotypic overlap with GLI‐related syndromes. Phenotypic analysis of mice with compromised cilia function has revealed new aspects of Gli regulation demonstrating the utility of mouse models in the characterisation of novel disease phenotypes. Key Concepts: Balance of GLI activator and repressor is required for normal development. Shift of the balance towards low or high GLI3R levels results in severe congenital malformations. Shift of the balance towards high GLI activator results in cancer. Mutations affecting different domains of bifunctional transcription factor Gli3 give rise to distinct phenotypes. Mutations affecting Hh pathway machinery affect Gli processing and activity and result in Gli‐related phenotypes. The primary cilium is critical for Hh signal transduction. Mutations in regulators of primary cilia structure and function result in ciliopathies, which share many overlapping phenotypes with GLI‐associated syndromes.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Other · Consensus signal: Other
Teacher disagreement score0.350
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.268
Teacher spread0.251 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designNot applicable
Domainnot available
GenreOther

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2012
Admission routes1
Has abstractyes

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