TMX3: Thioredoxin-Related Transmembrane Protein 3
A key oxidoreductase in the endoplasmic reticulum with roles in protein folding and redox homeostasis.
Gene Information Card
| Symbol | TMX3 |
|---|---|
| Full Name | Thioredoxin-Related Transmembrane Protein 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q22.1 |
| NCBI Gene ID | 54495 ncbi.nlm.nih.gov/gene/54495 |
| Ensembl ID | ENSG00000168497 |
| UniProt ID | Q96JJ7 |
| OMIM ID | 616216 |
| HGNC ID | 1356 |
| Aliases | PDIA13, TXNDL, TMX3_HUMAN |
Description
TMX3 encodes a transmembrane protein of the endoplasmic reticulum (ER) belonging to the protein disulfide isomerase (PDI) family. It contains a thioredoxin-like domain with a CXXC active site motif and functions as an oxidoreductase, catalyzing the formation, reduction, and isomerization of disulfide bonds in nascent proteins. TMX3 is involved in ER redox homeostasis and quality control, and its expression is associated with various cancers and developmental processes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | TMX3 overexpression may promote tumor cell survival by enhancing ER stress resistance and redox buffering. | COSMIC; literature (PMID: 25691885) |
| Developmental disorders | Rare missense variants in TMX3 have been reported in individuals with intellectual disability and congenital anomalies, suggesting a role in neurodevelopment. | ClinVar; literature (PMID: 28135719) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Thyroid | 9.8 | Medium |
| Adrenal gland | 8.2 | Medium |
| Liver | 6.1 | Low |
| Brain | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | High expression in cervical cancer line |
| HepG2 | 10.1 | Moderate expression in liver cancer line |
| A549 | 8.7 | Moderate expression in lung cancer line |
| MCF7 | 6.4 | Low expression in breast cancer line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.374C>T (p.Thr125Met) | Missense | 0.0004 (gnomAD) | Substitution in thioredoxin domain; potential impact on redox activity |
| c.1A>G (p.Met1Val) | Start loss | <0.0001 | Loss of translation initiation; likely loss-of-function |
| c.1036C>T (p.Arg346*) | Nonsense | <0.0001 | Premature stop; predicted loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and start-loss variants (e.g., p.Arg346*, p.Met1Val) are predicted to cause loss of TMX3 function through truncation or absence of protein.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TMX3.
Dominant Negative (DN)
Missense variants in the thioredoxin domain (e.g., p.Thr125Met) may act in a dominant-negative manner by interfering with dimerization or substrate binding, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endoplasmic reticulum protein processing (KEGG: hsa04141)
• Protein folding and ER stress response (Reactome: R-HSA-9014519)
Protein Summary
TMX3 is a 454-amino-acid transmembrane protein anchored in the ER membrane. It contains an N-terminal signal peptide, a thioredoxin-like domain with a CXXC (CPAC) active site, and a C-terminal transmembrane domain. The protein acts as an oxidoreductase, catalyzing disulfide bond formation and isomerization in client proteins. TMX3 is widely expressed, with highest levels in testis and thyroid. It interacts with other PDI family members and may play a role in ER stress adaptation. Structural studies indicate that the thioredoxin domain adopts a typical α/β fold with a redox-active disulfide bond.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMX3 Knockout HEK293 Cell Line | EDJ-KQ11439 | Human | 54495 | Details Get a Quote |
| TMX3 Knockout A-549 Cell Line | EDJ-KQ39703 | Human | 54495 | Details Get a Quote |
| TMX3 Knockout HCT 116 Cell Line | EDJ-KQ39704 | Human | 54495 | Details Get a Quote |
| TMX3 Knockout HeLa Cell Line | EDJ-KQ39705 | Human | 54495 | Details Get a Quote |
