Ask about this productRelated genes to: TMPRSS6 Blocking Peptide
- Gene:
- TMPRSS6 NIH gene
- Name:
- transmembrane serine protease 6
- Previous symbol:
- -
- Synonyms:
- FLJ30744
- Chromosome:
- 22q12.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-12-17
- Date modifiied:
- 2019-04-23
Related products to: TMPRSS6 Blocking Peptide
Related articles to: TMPRSS6 Blocking Peptide
- Heart failure (HF) is frequently associated with iron deficiency and anemia, negatively impacting patient outcomes. This study aimed to investigate the contribution of genetic variation in iron metabolism-related genes to biochemical and hematological phenotypes in HF. An HF population of 182 patients with functional iron deficiency (ID) and anemia was stratified by sex and heart failure subtype, including HF with reduced ejection fraction (HFrEF) and HF with non-reduced ejection fraction (HFnrEF). Genetic variants in (rs1799945), (rs1439816, rs2304704), and (rs855791) were evaluated. Variants in and were associated with differences in serum iron, ferritin, transferrin saturation, hemoglobin, and RDW. The phenotypic impact of these variants was modulated by sex and heart failure subtype, highlighting the influence of iron availability, inflammatory burden, and erythropoietic demand. In contrast, no significant associations were observed for the variant. In conclusion, genetic variation in key regulators of iron metabolism contributes to the heterogeneity of iron-related biochemical and hematological phenotypes in HF. These findings emphasize the interplay between genetic background, sex, and heart failure physiology and support the relevance of personalized approaches to iron assessment and management in heart failure. - Source: PubMed
Publication date: 2026/04/23
Barbosa MárioAguiar LauraMatias AnaFerreira JoanaCaldeira JoãoMelício AnaFaustino PaulaFalcão Luiz MenezesBicho ManuelInácio Ângela - Hepcidin is the central regulator of iron homeostasis, controlling iron sequestration and dietary iron absorption. Transmembrane serine protease 6 (TMPRSS6) suppresses hepcidin via the bone morphogenetic protein/small mothers against decapentaplegic (BMP/SMAD) pathway by cleaving the co-receptor hemojuvelin. DISC-3405 is a novel humanized monoclonal antibody that enhances hepcidin expression by inhibiting TMPRSS6, thereby promoting iron restriction. This Phase 1 study evaluated the safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of DISC-3405 or placebo in 56 healthy participants. DISC-3405 (37.5 to 300 mg) or placebo was administered subcutaneously (SC) or intravenously (IV). DISC-3405 was well tolerated. No deaths, serious adverse events, or participant discontinuations occurred. Most treatment-emergent adverse events were Grade 1 (mild) in severity, with 2 participants reporting Grade 2 (moderate) events following single dosing and no Grade 3/4 (severe/life-threatening) events reported. Median time to maximum plasma concentration was ≈96 to 168 h. Elimination half-life rose from 130 h at 37.5 mg to 265 h at 300 mg, with a clinically relevant half-life of ≈11 days. Absolute bioavailability was 39.7% (75 mg SC vs. IV). Minor accumulation occurred with repeat 4-week dosing of two doses, and PK was greater than dose proportional. DISC-3405 increased hepcidin-25 and reduced serum iron and transferrin saturation across dose levels. Single and repeated dosing of DISC-3405 produced reductions in reticulocyte hemoglobin, hemoglobin, and hematocrit. Overall, DISC-3405 was well tolerated with PK/PD data supporting further development for patients who could benefit from iron restriction, such as those with polycythemia vera. - Source: PubMed
Liu GuowenHowell HaleyCarden Marcus AYang HuaSavage Will - Non-transfusion dependent β-thalassemia (NTDT) is characterized by ineffective erythropoiesis, suppression of hepcidin, and iron overload, which is a major cause of morbidity and mortality. Hepatic protease Tmprss6 regulates hepcidin by modulating BMP/Smad signaling. Suppression of Tmprss6 in the mouse model of NTDT (Th3 mice), increased hepcidin and improved disease outcomes, but similar benefits have not been reported in human trials. We hypothesized that the resistance to the effects of anti-TMPRSS6 treatment in patients with NTDT may be caused by high erythroferrone (ERFE) concentrations and more severe iron overload, both known to modulate BMP/Smad signaling in hepatocytes. We therefore examined how ERFE and iron overload modulate the effects of Tmprss6 antisense oligonucleotides (ASO) in mouse models.We treated ERFE-overexpressing Th3 mice (T-E(M)) and their littermates (wild-type, Th3, and Erfe-overexpressing E(M) mice) with Tmprss6 ASO or non-targeting ASO for 4 weeks. Tmprss6 ASO increased phospho-Smad1/5/8 and hepcidin levels, decreased splenomegaly, reduced extramedullary erythropoiesis and improved iron parameters in Th3 mice but not in T-E(M) mice, despite similar Tmprss6 decrease. To determine whether iron overload alone blunted the effects of Tmprss6 ASO, we assessed the responses of C57BL/6 mice after 10 mg of iron dextran or 5000 ppm high iron diet. Unlike iron-adequate mice, iron-overloaded mice already had high phospho-Smad and hepcidin, with no further increase after Tmprss6 ASO treatment, and no effect on erythroid or iron parameters.Higher ERFE concentrations and more severe iron overload may be responsible for diminished benefits of Tmprss6 ASO in human NTDT. - Source: PubMed
Publication date: 2026/04/09
Zhang VidaBarrett Terrance DNemeth ElizabetaGanz Tomas - Liver steatosis, fibroinflammation, and iron overload, are growing global health concerns, yet the genetic architecture and causal pathways linking liver pathology to systemic disease remain incompletely understood. - Source: PubMed
Publication date: 2026/02/28
Meena DevendraPansini MicheleFichera AlessandroHuang JingxianAhmed AltayebDehghan AbbasBanerjee RajarshiYaghootkar Hanieh - Iron deficiency, anemia, and infection are global health challenges with overlapping geographical distributions, particularly affecting pregnant women in Africa, yet the mechanisms underlying their interactions remain poorly understood. We used a multilayered approach combining clinical data from Malawian pregnant women ( = 711) in the REVAMP trial, a genetic mouse model [-knockout (KO)], and in vitro cultures to clarify iron-malaria associations. Iron deficiency was associated with 50% reduced parasitemia in pregnant women [95% CI (30 to 64%), < 0.0001], while iron-deficient mice exhibited improved survival against (median 15.5 days versus 7.0 days for WT mice) and protection from cerebral malaria (83% versus 17% survival). Iron chelation substantially changed the transcriptomic and proteomic profile of cultured parasites. Intravenous iron supplementation did not increase parasitemia when coupled with malaria prevention. These findings demonstrate that iron deficiency protects against infection and support World Health Organization recommendations for iron supplementation in malaria-endemic regions when combined with adequate malaria prevention strategies in place. - Source: PubMed
Publication date: 2026/02/27
Clucas DanielleBennett CavanHarding RebeccaPettikiriarachchi AnneBaldi AndrewRandall Louise MSteel RyanMellin RonanHobbs MelissaCaiazzo SabrinaMwangi Martin NFielding Katherine LHickey Peter FBaldwin Tracey MAmann-Zalcenstein DanielaEmery-Corbin Samantha JMzembe GloryMoya ErnestBraat SabineJex AaronDemir Ayse YVerhoef HansPhiri Kamija SBiggs Beverley-AnnTham Wai-HongBoddey Justin APasricha Sant-RaynAtaíde Ricardo