The HNF4A Q164X Mutation Impairs Transcriptional Activation in Vitro but Its Heterozygosity Suppresses Liver Tumorigenesis in Vivo
Bibliographic record
Abstract
Abstract Hepatocyte nuclear factor 4 alpha (HNF4A) is a master regulator of hepatic differentiation and metabolism. Here, we identify and characterize a truncating Q164X mutation that impairs HNF4A transcriptional activity in vitro and causes embryonic lethality when homozygous. Functional assays revealed that the Q164X protein retains nuclear localization but exhibits severely reduced DNA binding and transcriptional activation. CRISPR-generated Q164X mice showed no viable homozygotes, confirming the essential role of HNF4A in early embryogenesis. Unexpectedly, heterozygous Q164X mutants displayed reduced liver tumorigenesis following diethylnitrosamine and high-fat diet treatment, despite downregulation of HNF4A target genes such as ApoB and Hnf1a . These results suggest that partial HNF4A deficiency may trigger compensatory metabolic networks that protect against carcinogenic stress. Collectively, our study establishes Q164X as a loss-of-function HNF4A mutation with paradoxical tumor-suppressive effects in vivo.
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 machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".