TMPRSS6
Transmembrane Serine Protease 6 (Matriptase-2) – Iron Regulation Gene
Gene Information Card
| Symbol | TMPRSS6 |
|---|---|
| Full Name | Transmembrane Serine Protease 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.3 |
| NCBI Gene ID | 164656 ncbi.nlm.nih.gov/gene/164656 |
| Ensembl ID | ENSG00000187045 |
| UniProt ID | Q8IU80 |
| OMIM ID | 609862 |
| HGNC ID | 29517 |
| Aliases | MT2, matriptase-2, IRIDA |
Description
TMPRSS6 encodes matriptase-2, a type II transmembrane serine protease that negatively regulates hepcidin expression by cleaving hemojuvelin (HJV) on hepatocyte membranes. This suppression of hepcidin allows increased iron absorption and release from stores. Loss-of-function mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA) due to inappropriately high hepcidin levels.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Iron-refractory iron deficiency anemia (IRIDA) | Loss-of-function mutations reduce matriptase-2 activity, leading to elevated hepcidin and impaired iron absorption | OMIM #206200; multiple case reports in ClinVar and literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Pancreas | 3.2 | Low |
| Kidney | 2.1 | Low |
| Small intestine | 1.8 | Low |
| Testis | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.3 | Hepatocyte model |
| HEK293 (embryonic kidney) | 8.7 | Overexpression studies |
| Caco-2 (intestinal) | 4.1 | Enterocyte model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2207G>A (p.Cys736Tyr) | Missense | Rare | Loss of proteolytic activity; IRIDA |
| c.2086C>T (p.Arg696Trp) | Missense | Rare | Impaired hemojuvelin cleavage; IRIDA |
| c.1906C>T (p.Arg636Ter) | Nonsense | Rare | Truncated protein; IRIDA |
| c.2536G>A (p.Gly846Arg) | Missense | Rare | Reduced cell surface expression; IRIDA |
Mutation functional classification
Loss of Function (LOF)
Most TMPRSS6 mutations are loss-of-function, leading to reduced matriptase-2 activity, elevated hepcidin, and iron deficiency anemia (IRIDA).
Gain of Function (GOF)
No gain-of-function mutations are clinically reported; such variants would theoretically suppress hepcidin excessively and cause iron overload.
Dominant Negative (DN)
Not described; IRIDA is typically autosomal recessive with biallelic loss-of-function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hepcidin regulation by matriptase-2 (Reactome R-HSA-917937)
• Iron uptake and transport (KEGG hsa04978)
Protein Summary
Matriptase-2 (TMPRSS6) is a 120 kDa type II transmembrane serine protease expressed primarily in the liver. It contains a short cytoplasmic tail, a transmembrane domain, and an extracellular serine protease domain. The protein negatively regulates hepcidin expression by cleaving membrane-bound hemojuvelin, thereby reducing BMP/SMAD signaling. Loss of matriptase-2 function leads to elevated hepcidin, causing iron-refractory iron deficiency anemia (IRIDA).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMPRSS6 Knockout HEK293 Cell Line | EDJ-KQ12152 | Human | 164656 | Details Get a Quote |
| TMPRSS6 Knockout HeLa Cell Line | EDJ-KQ58878 | Human | 164656 | Details Get a Quote |
| TMPRSS6 Knockout A-549 Cell Line | EDJ-KQ67369 | Human | 164656 | Details Get a Quote |
| TMPRSS6 Knockout HCT 116 Cell Line | EDJ-KQ75762 | Human | 164656 | Details Get a Quote |
