FOXA2
Chr 20forkhead box A2
Also known as: HNF-3-beta, HNF3B, TCF3B
This gene encodes a forkhead transcription factor that acts as a pioneer factor to open chromatin and regulate gene expression during embryonic development and in differentiated tissues, particularly in endoderm-derived organs including liver, pancreas, and lungs. Mutations cause maturity-onset diabetes of the young (MODY), which typically presents in adolescence or young adulthood with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.477), consistent with its essential role in pancreatic beta-cell function and glucose homeostasis.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
195 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 19 | 0 | 19 |
Likely Pathogenic | 0 | 1 | 4 | 0 | 5 |
VUS | 7 | 92 | 6 | 1 | 106 |
Likely Benign | 0 | 10 | 1 | 29 | 40 |
Benign | 0 | 7 | 0 | 7 | 14 |
Conflicting | — | 7 | |||
| Total | 7 | 110 | 30 | 37 | 191 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FOXA2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools