TRA2A (Transformer 2 Alpha Homolog): RNA Splicing Regulator and Disease Implications
A comprehensive overview of TRA2A, a serine/arginine-rich splicing factor involved in pre-mRNA processing, with implications in cancer and genetic disorders.
Gene Information Card
| Symbol | TRA2A |
|---|---|
| Full Name | Transformer 2 Alpha Homolog |
| Gene Type | Protein coding |
| Chromosomal Location | 7p15.3 |
| NCBI Gene ID | 29896 ncbi.nlm.nih.gov/gene/29896 |
| Ensembl ID | ENSG00000164588 |
| UniProt ID | Q13595 |
| OMIM ID | 602289 |
| HGNC ID | 11995 |
| Aliases | AWMS2, HSU53209, TRA2-alpha, SFRS10 |
Description
TRA2A encodes a serine/arginine-rich (SR) protein that functions as a splicing factor. It binds to pre-mRNA and regulates alternative splicing, influencing gene expression and cellular processes. TRA2A is involved in various biological contexts, including neuronal development, immune response, and cancer progression. Its expression is ubiquitous but varies across tissues, and dysregulation has been linked to several diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | TRA2A overexpression or altered splicing activity can promote tumorigenesis by modulating oncogene and tumor suppressor splicing. | COSMIC lists TRA2A as a gene with mutations in cancer samples; multiple studies (referenced in NCBI) indicate altered expression in tumors. |
| Neurodevelopmental disorders | TRA2A regulates splicing of genes critical for neuronal function; mutations may contribute to intellectual disability or autism spectrum disorders. | ClinVar reports variants of uncertain significance in TRA2A associated with neurodevelopmental phenotypes. |
| Genetic disorders (e.g., microcephaly) | Loss-of-function mutations in TRA2A may impair brain development due to defective splicing of essential genes. | OMIM entry 602289 notes a phenotype of autosomal recessive primary microcephaly linked to TRA2A mutations. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Testis | 12.8 | Medium |
| Lung | 8.5 | Low |
| Liver | 6.3 | Low |
| Heart | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 18.4 | High expression; used in splicing studies |
| K562 (leukemia) | 14.2 | Moderate expression |
| MCF7 (breast cancer) | 12.1 | Moderate expression |
| HepG2 (liver cancer) | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.574C>T (p.Arg192Ter) | Nonsense | Rare (0.01% in gnomAD) | Predicted to cause loss of function via nonsense-mediated decay. |
| c.832G>A (p.Gly278Arg) | Missense | 0.05% in cancer samples (COSMIC) | May affect RNA-binding affinity; potential gain-of-function in splicing regulation. |
| c.1024A>G (p.Ile342Val) | Missense | 0.02% in general population | Uncertain significance; possibly benign. |
Mutation functional classification
Loss of Function (LOF)
Nonsense or frameshift mutations leading to truncated protein or mRNA decay, reducing splicing activity. Associated with microcephaly and neurodevelopmental defects.
Gain of Function (GOF)
Missense mutations that enhance TRA2A's binding to RNA or alter splicing patterns, potentially promoting oncogenic splicing variants in cancer.
Dominant Negative (DN)
Mutations that produce a protein interfering with wild-type TRA2A function, disrupting normal splicing regulation; observed in some cancer cell lines.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • mRNA binding (GO:0003729) |
| • nucleotide binding (GO:0000166) | • nucleus (GO:0005634) |
| • nuclear speck (GO:0016607) | • mRNA processing (GO:0006397) |
| • RNA splicing (GO:0008380) | • regulation of alternative mRNA splicing |
| • via spliceosome (GO:0000381) |
Pathways
• mRNA Splicing - Major Pathway (Reactome: R-HSA-72163)
• Processing of Capped Intron-Containing Pre-mRNA (Reactome: R-HSA-72203)
• Gene Expression (Reactome: R-HSA-74160)
Protein Summary
TRA2A is a 282-amino acid protein containing an RNA recognition motif (RRM) and an SR domain. It binds to specific RNA sequences, such as (A/G)AA repeats, and recruits spliceosomal components to regulate alternative splicing. TRA2A interacts with other SR proteins and can either promote or repress exon inclusion depending on context. Post-translational phosphorylation of the SR domain modulates its activity and subcellular localization. TRA2A is predominantly nuclear, localizing to speckles, and is involved in the splicing of genes related to cell cycle, apoptosis, and differentiation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRA2A Knockout HEK293 Cell Line | EDC90653 | Human | 29896 | Details Get a Quote |
| TRA2A Knockout HeLa Cell Line | EDJ-KQ34294 | Human | 29896 | Details Get a Quote |
| TRA2A Knockout A-549 Cell Line | EDJ-KQ35546 | Human | 29896 | Details Get a Quote |
| TRA2A Knockout HCT 116 Cell Line | EDJ-KQ35547 | Human | 29896 | Details Get a Quote |
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