TGFA
protein-codingtransforming growth factor alpha
Gene summary
This gene encodes a growth factor that is a ligand for the epidermal growth factor receptor, which activates a signaling pathway for cell proliferation, differentiation and development. This protein may act as either a transmembrane-bound ligand or a soluble ligand. This gene has been associated with many types of cancers, and it may also be involved in some cases of cleft lip/palate. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~106.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005486
Submitter: Orphanet
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TGFA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003236.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 25 | 1 | 1 | 27 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 26 | 1 | 3 | 30 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003227.1 | 6 | MANE Select | |
| Ensembl | ENSP00000295400.6 | 6 | MANE Select | |
| RefSeq | NP_001093161.1 | 6 | Standard | |
| RefSeq | NP_001295087.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Non-small cell lung cancer - Homo sapiens (human)
- Renal cell carcinoma - Homo sapiens (human)
- ErbB signaling pathway - Homo sapiens (human)
- Hepatocellular carcinoma - Homo sapiens (human)
Biological Process
- activation of MAPK activity
- regulation of transcription by RNA polymerase II
- endoplasmic reticulum to Golgi vesicle-mediated transport
- epidermal growth factor receptor signaling pathway
- cell population proliferation
Molecular Function
- epidermal growth factor receptor binding
- protein binding
- growth factor activity
Cellular Component
- Golgi membrane
- extracellular space
- endoplasmic reticulum membrane
- plasma membrane
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000295400
- Coding exons
- 6
- Length
- 106914
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125729
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.758 | 72 | 92.5 | 0.778 | 0.00000532 | 1010 |
| Missense (PolyPhen) | 19 | 27.924 | 0.68042 | 334 | ||
| Synonymous | 1.00 | 34 | 42.3 | 0.804 | 0.00000289 | 320 |
| Loss of Function | 2.39 | 1 | 8.51 | 0.118 | 4.49e-7 | 95 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: TGF alpha is a mitogenic polypeptide that is able to bind to the EGF receptor/EGFR and to act synergistically with TGF beta to promote anchorage-independent cell proliferation in soft agar.;
Recessive Scores
- pRec
- 0.750
Intolerance Scores
- LoFtool
- 0.599
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.959
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |