GRHL2: Grainyhead Like Transcription Factor 2
Key regulator of epithelial development, barrier function, and cancer progression
Gene Information Card
| Symbol | GRHL2 |
|---|---|
| Full Name | Grainyhead Like Transcription Factor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q22.3 |
| NCBI Gene ID | 79977 ncbi.nlm.nih.gov/gene/79977 |
| Ensembl ID | ENSG00000183307 |
| UniProt ID | Q6ISB3 |
| OMIM ID | 608576 |
| HGNC ID | 27999 |
| Aliases | BOM, TFCP2L3, grainyhead-like 2 |
Description
GRHL2 encodes a member of the grainyhead family of transcription factors, characterized by a CP2-type DNA-binding domain. The protein plays a critical role in epithelial development, maintenance of epithelial barrier integrity, and regulation of epithelial-to-mesenchymal transition (EMT). GRHL2 is involved in neural tube closure, hearing, and kidney development. Dysregulation of GRHL2 is associated with various cancers and hereditary hearing loss.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant deafness 28 (DFNA28) | Missense mutations in GRHL2 disrupt transcriptional activity required for cochlear hair cell function | ClinVar, OMIM |
| Breast cancer | GRHL2 suppresses EMT; loss of expression correlates with invasive phenotype | NCBI Gene, COSMIC |
| Colorectal cancer | GRHL2 overexpression promotes tumor growth and metastasis via Wnt/β-catenin signaling | COSMIC, PubMed |
| Ovarian cancer | GRHL2 regulates cell adhesion and invasion; altered expression linked to poor prognosis | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 42.3 | High |
| Lung | 28.7 | Medium |
| Breast | 35.1 | High |
| Colon | 30.5 | Medium |
| Liver | 12.4 | Low |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 45.6 | High expression |
| A549 (lung cancer) | 22.3 | Moderate expression |
| HCT116 (colorectal cancer) | 38.9 | High expression |
| HEK293 (embryonic kidney) | 50.1 | Very high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1061C>T (p.Thr354Met) | Missense | Rare | Reduced transcriptional activity; associated with DFNA28 |
| c.1609G>A (p.Gly537Arg) | Missense | Rare | Impaired DNA binding; hearing loss |
| c.1250_1251del (p.Gln417Argfs*12) | Frameshift | Very rare | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt the DNA-binding domain lead to loss of transcriptional activity.
Gain of Function (GOF)
Not well documented; some missense variants may enhance activity but require further study.
Dominant Negative (DN)
Missense mutations in the dimerization domain can interfere with wild-type GRHL2 function, contributing to autosomal dominant hearing loss.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Epithelial-to-mesenchymal transition (EMT) regulation
• Wnt/β-catenin signaling pathway
• Hippo signaling pathway (via TEAD interaction)
• TGF-β signaling pathway
Protein Summary
GRHL2 is a 625-amino acid transcription factor containing a CP2-type DNA-binding domain and a dimerization domain. It localizes to the nucleus and binds to specific DNA sequences to regulate genes involved in epithelial cell adhesion, polarity, and barrier function. GRHL2 acts as a master regulator of epithelial identity by repressing EMT inducers such as ZEB1 and SNAI2. The protein also interacts with other transcription factors (e.g., OVOL2) to maintain epithelial homeostasis. In cancer, GRHL2 can function as either a tumor suppressor or oncogene depending on context.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRHL2 Knockout HEK293 Cell Line | EDJ-KQ13684 | Human | 79977 | Details Get a Quote |
| GRHL2 Knockout HCT 116 Cell Line | EDJ-KQ43387 | Human | 79977 | Details Get a Quote |
| GRHL2 Knockout HeLa Cell Line | EDJ-KQ57270 | Human | 79977 | Details Get a Quote |
| GRHL2 Knockout A-549 Cell Line | EDJ-KQ65780 | Human | 79977 | Details Get a Quote |
