TGFA: Transforming Growth Factor Alpha
A key ligand of the epidermal growth factor receptor (EGFR) involved in cell proliferation, differentiation, and development.
Gene Information Card
| Symbol | TGFA |
|---|---|
| Full Name | Transforming Growth Factor Alpha |
| Gene Type | protein-coding |
| Chromosomal Location | 2p13.3 |
| NCBI Gene ID | 7039 ncbi.nlm.nih.gov/gene/7039 |
| Ensembl ID | ENSG00000163235 |
| UniProt ID | P01135 |
| OMIM ID | 190170 |
| HGNC ID | 11765 |
| Aliases | TFGA, TGF-alpha |
Description
The TGFA gene encodes transforming growth factor alpha (TGF-α), a mitogenic polypeptide that binds to the epidermal growth factor receptor (EGFR). TGF-α stimulates cell proliferation, differentiation, and migration, playing critical roles in embryonic development, wound healing, and oncogenesis. It is synthesized as a transmembrane precursor that is cleaved to release the soluble growth factor.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cleft lip with or without cleft palate | Altered TGF-α signaling disrupts craniofacial development; genetic association studies implicate TGFA variants. | PMID: 10807689, OMIM #119530 |
| Various cancers (e.g., breast, lung, colorectal) | Overexpression of TGF-α leads to autocrine EGFR activation, promoting uncontrolled cell proliferation and tumor progression. | PMID: 10646847, COSMIC |
| Psoriasis | Elevated TGF-α levels in psoriatic skin contribute to keratinocyte hyperproliferation. | PMID: 1371292 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Esophagus | 8.3 | Medium |
| Kidney | 6.1 | Low |
| Liver | 4.2 | Low |
| Brain | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A-431 (epidermoid carcinoma) | 45.2 | High expression; consistent with EGFR autocrine loop |
| MCF7 (breast cancer) | 18.7 | Moderate expression |
| HeLa (cervical cancer) | 9.5 | Low expression |
| HEK 293 (embryonic kidney) | 3.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Likely loss of start codon; predicted loss of function |
| c.364C>T (p.Arg122Trp) | missense | <0.01% | Unknown significance; rare population variant |
| c.482G>A (p.Arg161Gln) | missense | <0.01% | Unknown significance; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Rare missense or nonsense variants that impair TGF-α synthesis or receptor binding are predicted to reduce EGFR signaling, potentially affecting development.
Gain of Function (GOF)
Amplification or overexpression of TGFA (not point mutations) is the primary gain-of-function mechanism in cancer, leading to sustained EGFR activation.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for TGFA.
View complete mutation data：
Gene Ontology (GO)
Pathways
• EGFR tyrosine kinase inhibitor resistance (KEGG: hsa01521)
• ErbB signaling pathway (KEGG: hsa04012)
• Regulation of lipolysis in adipocytes (KEGG: hsa04923)
Protein Summary
Transforming growth factor alpha (TGF-α) is a 160-amino-acid mature protein (after signal peptide cleavage) that belongs to the EGF family. It contains a conserved EGF-like domain with six cysteine residues forming three disulfide bonds essential for receptor binding. TGF-α is synthesized as a 160-residue transmembrane precursor (proTGF-α) that is proteolytically cleaved by ADAM17 (TACE) to release the soluble ligand. The soluble form binds EGFR with high affinity, inducing receptor dimerization and autophosphorylation, which activates downstream signaling cascades including MAPK, PI3K/AKT, and STAT pathways. TGF-α is widely expressed in epithelial tissues and is upregulated in many cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TGFA Knockout HEK293 Cell Line | EDJ-KQ241 | Human | 7039 | Details Get a Quote |
| TGFA Knockout A-549 Cell Line | EDJ-KQ19434 | Human | 7039 | Details Get a Quote |
| TGFA Knockout HCT 116 Cell Line | EDJ-KQ19435 | Human | 7039 | Details Get a Quote |
| TGFA Knockout HeLa Cell Line | EDJ-KQ19436 | Human | 7039 | Details Get a Quote |
