GRHL2
Chr 8ADARgrainyhead like transcription factor 2
Also known as: BOM, DFNA28, ECTDS, PPCD4, TFCP2L3
This gene encodes a transcription factor that binds to specific DNA sequences to regulate epithelial development, primary neurulation, and expression of tight junction proteins including claudins. Mutations cause autosomal dominant non-syndromic sensorineural deafness (DFNA28), posterior polymorphous corneal dystrophy type 4, and autosomal recessive ectodermal dysplasia with short stature. The pathogenic mechanism involves loss of function, as the protein is highly intolerant to loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
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
200 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 | 9 | 0 | 4 | 0 | 13 |
Likely Pathogenic | 8 | 0 | 0 | 0 | 8 |
VUS | 1 | 101 | 9 | 1 | 112 |
Likely Benign | 0 | 2 | 27 | 21 | 50 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 18 | 103 | 40 | 23 | 184 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GRHL2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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