Property Summary

NCBI Gene PubMed Count 84
PubMed Score 118.15
PubTator Score 129.08

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (5)

Disease log2 FC p
osteosarcoma 1.840 2.9e-06
medulloblastoma, large-cell 1.200 3.7e-03
adult high grade glioma 1.200 8.0e-04
pituitary cancer 1.300 1.7e-02
psoriasis -2.800 4.3e-93

Gene RIF (71)

PMID Text
26405152 Combination of Tmprss6- ASO and the iron chelator deferiprone improves erythropoiesis and reduces iron overload in a mouse model of beta-thalassemia intermedia.
26385264 Data show that p.V736A TMPRSS6 variant (rs855791) influences the susceptibility to hepatic iron accumulation in NTDT patients, and the risk allele is 736(A).
26171609 N-glycan branching regulates HAI-2 through different subcellular distribution and subsequently access to different target proteases
25873000 A novel splicing mutation of TMPRSS6 exon 9 (c.1113G>A) was found in an iron-refractory iron deficiency anemia patient and his father.
25809685 genetic association studies in a population of black women in South Africa: Data suggest that SNPs in TMPRSS6 (rs228918; rs228921) are associated with iron status/iron-deficiency anemia in the population studied.
25704252 Data show that transmembrane serine protease TMPRSS6 cleaves both the heterodimeric and the full-length mutant hemojuvelin (m-HJV).
25588876 Certain domains of matriptase-2 are important for trafficking to the cell surface and are required for cleavage of hemojuvelin.
25567183 genetic variation in TMPRSS6 is higher in celiac disease patients than in controls.
25557470 TMPRSS6 polymorphisms could play a role in iron homeostasis and the response to oral iron supplementation.
25156943 We confirm that TMPRSS6 mutations are spread along the gene and that mechanistically they fully or partially abrogate hepcidin inhibition.
24867957 these data provide new insights into the cell surface expression, zymogen activation, and ectodomain shedding of matriptase-2.
24782651 Our study suggests homozygosity for TMPRSS6 rs855791 C genotype has a protective role against IDA in women at reproductive age, especially in those with menorrhagia.
24661031 Correspondence You have free access to this content A novel tri-allelic mutation of TMPRSS6 in iron-refractory iron deficiency anaemia with response to glucocorticoid.
24382527 report six patients from three unrelated families with mutations in the TMPRSS6 gene, with three of the four identified mutations being novel
24376517 TMPRSS6 inhibition via decreased STAT5 phosphorylation may be an additional mechanism by which inflammation stimulates hepcidin expression to regulate iron homeostasis and immunity.
24175968 In a study of 545 Rwandan pre-school children, 34.4% had anemia (17.6% Iron Deficiency Anemia). The TMPRSS6 736(V) allele, known to reduce iron status and Hb levels, was no more common than other known causes of anemia.
23794717 Investigated and foung SNPs HFE rs1800562 and TMPRSS6 rs855791 are the main determinants of HFE and TMPRSS6 related variation in serum iron, ferritin, transferrin saturation, and total iron binding capacity.
23649491 The association of TMRRSS6 variants with breast cancer risk and survival.
23433094 A736V TMPRSS6 genotype influences hepcidin levels, erythropoiesis, and anemia management in CHD patients.
23293981 data demonstrate that TMPRSS6 variations are very frequently associated with iron deficiency anaemia in patients suffering from polyendocrine autoimmune syndrome type III
23293962 HAI-2 is an inhibitor of matriptase-2 that modulates the synthesis of hepcidin.
23238872 Matriptase-2 could have a potential role in prostate and breast tumour suppression through its anti-angiogenic properties.
23144979 The p.Ala736Val TMPRSS6 variant influences secondary hepatic iron accumulation in patients with nonalcoholic fatty liver disease (NAFLD).
22893705 neogenin forms a ternary complex with both MT2 and HJV at the plasma membrane. The complex facilitates HJV cleavage by MT2, and release of the cleaved HJV from the cell occurs after a retrograde trafficking through the TGN/Golgi compartments.
22885719 The p.A736V TMPRSS6 polymorphism is likely a modifier of Hereditary hemochromatosis (HH) expression.
22858929 matriptase-2 protects against the development and progression of prostate cancer by regulating the motility and invasive capabilities of prostate cancer cells
22765023 2 new TMPRSS6 variants associated, in the heterozygous form, with iron-refractory iron-deficiency anaemia (IRDA) in 2 unrelated families; data suggest although heterozygous TMPRSS6 mutations may not be able to induce a clear IRIDA phenotype, some may increase susceptibility to iron deficiency
22761678 Single nucleotide polymorphisms in TMPRSS6 gene is associated with iron overload.
22628316 action of HIF-1alpha on TMPRSS6 promoter activity
22581667 TMPRSS6 missense mutant proteins are targeted to the plasma membrane.
22509377 sequenced exons and exon-intron boundaries of SLC11A2 and TMPRSS6 in all 6 family members with iron-refractory iron deficiency anaemia; cannot exclude or confirm a gene-gene interaction between SLC11A2 and TMPRSS6; gene sequencing did not reveal causative rare mutations
22323359 TF, TFR2 and TMPRSS6 polymorphisms are significantly associated with decreased iron status, but only variants in TMPRSS6 are genetic risk factors for iron deficiency and iron-deficiency anemia.
22301935 TMPRSS6 variants were significantly associated with plasma ferritin, hemoglobin, risk of iron overload, and type 2 diabetes in Chinese Hans.
22265928 We observed no other significant relationship of TMPRSS6 K253E, A736V, or Y739Y with iron, erythrocyte, or pica phenotypes.
21873547 Data indicate that TMPRSS6 rs855791 has a functional role in determining protease activity and regulating hepcidin expression in normal subjects.
21785125 HFE rs1800562 C282Y variant exerts a direct pleiotropic effect on the iron parameters, in part independent of hepcidin.
21724843 the importance of TMPRSS6 trafficking at the plasma membrane in the regulation of hepcidin expression, an event that is essential for iron homeostasis.
21622652 Modulation of TMPRSS6 expression could serve as a negative feedback inhibitor to avoid excessive hepcidin increases by iron to help maintain tight homeostatic balance of systemic iron levels.
21618415 A novel mutation Gly603Arg of TMPRSS6 in a Korean female with iron-refractory iron deficiency anemia
21150441 Novel genetic forms of iron-related microcytic anemia have been identified, due to defects of iron transport/utilization or to TMPRSS6 deficiency and hepcidin hyperproduction.
20966077 Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis
20964721 Cryptic splice site usage leading to truncated TMPRSS6 is responsible for iron refractory iron deficiency anaemia in an Italian Family
20937842 Matriptase-2- and proprotein convertase-cleaved forms of hemojuvelin have different roles in the down-regulation of hepcidin expression
20927387 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
20858683 Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
20738301 in 16 subjects with iron-refractory iron deficiency anaemia (IRIDA), identified 27 polymorphisms in TMPRSS6 gene; 8 snps and 4 haplotypes were associated with iron-refractory anaemia
20704562 showed that it localizes to similar subcellular compartments as wild-type TMPRSS6 and binds HJV, but fails to auto-catalytically activate itself.
20587610 Observational study of gene-disease association. (HuGE Navigator)
20232450 Results extend the pattern of TMPRSS6 mutations associated with IRIDA and propose a model of causality for some of the novel missense mutation.
19907145 A key biologically relevant substrate for the proteolytic activity of matriptase-2/TMPRSS6 was found to be hemojuvelin, a cell surface protein that regulates hepcidin expression through a BMP/SMAD pathway
19880490 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
19862010 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
19820699 findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.
19820699 Observational study of gene-disease association. (HuGE Navigator)
19820698 findings suggest that TMPRSS6, a regulator of hepcidin synthesis and iron handling, is crucial in hemoglobin level maintenance.
19820698 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
19818657 investigation of genetic variations in TMPRSS6: polymorphisms & mutations in iron deficiency anemia; 3 uncommon non-synonymous polymorphisms were identified, G228D, R446W, & V795I; R446W polymorphism appeared to be overrepresented in the anemic population
19818657 Observational study of gene-disease association. (HuGE Navigator)
19708871 2 new cases of iron-refractory iron deficiency anaemia show the importance of LDLR-1/-2 & CUB1 domains in TMPRSS6 function and its role in hepcidin regulation.
19592582 TMPRSS6 mutations are associated with iron-refractory iron deficiency anemia.
19377077 Article summarized the functional relevance of matriptase-2 in iron metabolism.
18976966 Transmembrane protease serine 6 cleaves hemojuvelin a regulator of hepcidin, on plasma membrane; transmembrane protease serine 6 shows no cleavage activity and the human mutant only partial cleavage capacity.
18976966 TMPRSS6 role in iron metabolism and its interaction with HJV
18603562 TMPRSS6 mutation leads to overproduction of hepcidin and, in turn, to defective iron absorption and utilization
18449907 Data show that genetic upregulation of matriptase-2 reduces the aggressiveness of prostate cancer cells in vitro and in vivo and affects FAK and paxillin localisation.
18408718 These findings demonstrate that TMPRSS6 is essential for normal systemic iron homeostasis in humans.
17981570 identification, structural features, enzymology, expression pattern and potential roles of TMPRSS6 [review]
17575220 Matriptase-2 suppresses breast tumor development in vivo, displays prognostic value for breast cancer patients, inhibits both breast cancer cell invasion and motility in vitro, and may play a contrasting role to matriptase-1 in breast cancer
16533768 Observational study of gene-disease association. (HuGE Navigator)
16533768 Single Nucleotide Polymorphisms in TMPRSS6 is associated with breast cancer
12149247 a membrane-bound sereine proteinase predominantly expressed in human liver and showing degrading activity against extracellular matrix proteins

AA Sequence

MLLLFHSKRMPVAEAPQVAGGQGDGGDGEEAEPEGMFKACEDSKRKARGYLRLVPLFVLLALLVLASAGV      1 - 70
LLWYFLGYKAEVMVSQVYSGSLRVLNRHFSQDLTRRESSAFRSETAKAQKMLKELITSTRLGTYYNSSSV     71 - 140
YSFGEGPLTCFFWFILQIPEHRRLMLSPEVVQALLVEELLSTVNSSAAVPYRAEYEVDPEGLVILEASVK    141 - 210
DIAALNSTLGCYRYSYVGQGQVLRLKGPDHLASSCLWHLQGPKDLMLKLRLEWTLAECRDRLAMYDVAGP    211 - 280
LEKRLITSVYGCSRQEPVVEVLASGAIMAVVWKKGLHSYYDPFVLSVQPVVFQACEVNLTLDNRLDSQGV    281 - 350
LSTPYFPSYYSPQTHCSWHLTVPSLDYGLALWFDAYALRRQKYDLPCTQGQWTIQNRRLCGLRILQPYAE    351 - 420
RIPVVATAGITINFTSQISLTGPGVRVHYGLYNQSDPCPGEFLCSVNGLCVPACDGVKDCPNGLDERNCV    421 - 490
CRATFQCKEDSTCISLPKVCDGQPDCLNGSDEEQCQEGVPCGTFTFQCEDRSCVKKPNPQCDGRPDCRDG    491 - 560
SDEEHCDCGLQGPSSRIVGGAVSSEGEWPWQASLQVRGRHICGGALIADRWVITAAHCFQEDSMASTVLW    561 - 630
TVFLGKVWQNSRWPGEVSFKVSRLLLHPYHEEDSHDYDVALLQLDHPVVRSAAVRPVCLPARSHFFEPGL    631 - 700
HCWITGWGALREGGPISNALQKVDVQLIPQDLCSEVYRYQVTPRMLCAGYRKGKKDACQGDSGGPLVCKA    701 - 770
LSGRWFLAGLVSWGLGCGRPNYFGVYTRITGVISWIQQVVT                                 771 - 811
//

Text Mined References (88)

PMID Year Title
26405152 2016 Combination of Tmprss6- ASO and the iron chelator deferiprone improves erythropoiesis and reduces iron overload in a mouse model of beta-thalassemia intermedia.
26385264 2015 The V736A TMPRSS6 polymorphism influences liver iron concentration in nontransfusion-dependent thalassemias.
26171609 2015 N-Glycan Branching Affects the Subcellular Distribution of and Inhibition of Matriptase by HAI-2/Placental Bikunin.
25873000 2015 A novel splicing mutation of TMPRSS6 in a Chinese child with iron-refractory iron deficiency anaemia.
25809685 2015 Common Variants and Haplotypes in the TF, TNF-?, and TMPRSS6 Genes Are Associated with Iron Status in a Female Black South African Population.
25704252 2015 Identification of TMPRSS6 cleavage sites of hemojuvelin.
25588876 2015 Functional analysis of matriptase-2 mutations and domains: insights into the molecular basis of iron-refractory iron deficiency anemia.
25567183 2015 Does TMPRSS6 RS855791 polymorphism contribute to iron deficiency in treated celiac disease?
25557470 2015 The role of TMPRSS6 polymorphisms in iron deficiency anemia partially responsive to oral iron treatment.
25352340 2014 Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis.
25156943 2014 Functional and clinical impact of novel TMPRSS6 variants in iron-refractory iron-deficiency anemia patients and genotype-phenotype studies.
24867957 2014 N-glycosylation is required for matriptase-2 autoactivation and ectodomain shedding.
24782651 2014 TMPRSS6 rs855791 polymorphism influences the susceptibility to iron deficiency anemia in women at reproductive age.
24661031 2014 A novel tri-allelic mutation of TMPRSS6 in iron-refractory iron deficiency anaemia with response to glucocorticoid.
24382527 Is the acronym IRIDA acceptable for slow responders to iron in the presence of TMPRSS6 mutations?
24376517 2013 Inflammation regulates TMPRSS6 expression via STAT5.
24175968 2014 Anaemia, iron deficiency and a common polymorphism of iron-regulation, TMPRSS6 rs855791, in Rwandan children.
23935956 2013 Genome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans.
23794717 2013 Associations of common variants in HFE and TMPRSS6 with iron parameters are independent of serum hepcidin in a general population: a replication study.
23649491 2013 Matriptase-2 gene (TMPRSS6) variants associate with breast cancer survival, and reduced expression is related to triple-negative breast cancer.
23433094 2013 The A736V TMPRSS6 polymorphism influences hepcidin and iron metabolism in chronic hemodialysis patients: TMPRSS6 and hepcidin in hemodialysis.
23293981 2013 Very high frequency of TMPRSS6 gene variations in iron deficiency anaemia of patients with polyendocrine autoimmune syndromes: more than a casual association?
23293962 2013 Hepatocyte growth factor activator inhibitor type 2 (HAI-2) modulates hepcidin expression by inhibiting the cell surface protease matriptase-2.
23263863 2013 GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.
23238872 2013 Matriptase-2 inhibits HECV motility and tubule formation in vitro and tumour angiogenesis in vivo.
23222517 2012 Seventy-five genetic loci influencing the human red blood cell.
23144979 2012 The A736V TMPRSS6 polymorphism influences hepatic iron overload in nonalcoholic fatty liver disease.
22893705 2012 Neogenin interacts with matriptase-2 to facilitate hemojuvelin cleavage.
22885719 2012 Effect of the A736V TMPRSS6 polymorphism on the penetrance and clinical expression of hereditary hemochromatosis.
22858929 2012 The influence of matriptase-2 on prostate cancer in vitro: a possible role for ?-catenin.
22765023 2012 Two novel mutations in the tmprss6 gene associated with iron-refractory iron-deficiency anaemia (irida) and partial expression in the heterozygous form.
22761678 2012 Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations.
22628316 2012 Matriptase-2 (TMPRSS6) is directly up-regulated by hypoxia inducible factor-1: identification of a hypoxia-responsive element in the TMPRSS6 promoter region.
22581667 2012 Inactive matriptase-2 mutants found in IRIDA patients still repress hepcidin in a transfection assay despite having lost their serine protease activity.
22509377 2012 Candidate gene sequencing of SLC11A2 and TMPRSS6 in a family with severe anaemia: common SNPs, rare haplotypes, no causative mutation.
22323359 2012 TMPRSS6, but not TF, TFR2 or BMP2 variants are associated with increased risk of iron-deficiency anemia.
22301935 2012 Association of TMPRSS6 polymorphisms with ferritin, hemoglobin, and type 2 diabetes risk in a Chinese Han population.
22265928 2012 Common TMPRSS6 mutations and iron, erythrocyte, and pica phenotypes in 48 women with iron deficiency or depletion.
21873547 2011 TMPRSS6 rs855791 modulates hepcidin transcription in vitro and serum hepcidin levels in normal individuals.
21785125 2011 Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations.
21724843 2011 Essential role of endocytosis of the type II transmembrane serine protease TMPRSS6 in regulating its functionality.
21643693 2011 Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia.
21622652 2011 Regulation of TMPRSS6 by BMP6 and iron in human cells and mice.
21618415 2012 A novel mutation Gly603Arg of TMPRSS6 in a Korean female with iron-refractory iron deficiency anemia.
21208937 2011 Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels.
21150441 2011 Inherited disorders of iron metabolism.
21149283 2011 Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels.
20966077 2011 Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis.
20964721 2011 Cryptic splice site usage leading to truncated TMPRSS6 is responsible for iron refractory iron deficiency anaemia in an Italian Family.
20937842 2010 Matriptase-2- and proprotein convertase-cleaved forms of hemojuvelin have different roles in the down-regulation of hepcidin expression.
20927387 2010 A genome-wide association study of red blood cell traits using the electronic medical record.
20858683 2010 Common variants at 10 genomic loci influence hemoglobin A?(C) levels via glycemic and nonglycemic pathways.
20738301 2010 Genetic variability of TMPRSS6 and its association with iron deficiency anaemia.
20704562 2010 A novel TMPRSS6 mutation that prevents protease auto-activation causes IRIDA.
20587610 2010 Examination of genetic polymorphisms in newborns for signatures of sex-specific prenatal selection.
20518742 2010 Proteolytic processing of the serine protease matriptase-2: identification of the cleavage sites required for its autocatalytic release from the cell surface.
20232450 2010 Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia (IRIDA).
20139978 2010 Genome-wide association study of hematological and biochemical traits in a Japanese population.
19907145 2009 Role of matriptase-2 (TMPRSS6) in iron metabolism.
19880490 2010 A genome-wide association analysis of serum iron concentrations.
19862010 2009 Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
19853236 2009 Sequence variants in three loci influence monocyte counts and erythrocyte volume.
19820699 2009 Common variants in TMPRSS6 are associated with iron status and erythrocyte volume.
19820698 2009 Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels.
19820697 2009 A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.
19818657 2010 Polymorphisms and mutations of human TMPRSS6 in iron deficiency anemia.
19747362 2009 A novel splice site mutation c.2278 (-1) G>C in the TMPRSS6 gene causes deletion of the substrate binding site of the serine protease resulting in refractory iron deficiency anaemia.
19708871 2009 Haematologic data, iron parameters and molecular findings in two new cases of iron-refractory iron deficiency anaemia.
19592582 2009 Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms.
19377077 2009 Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis.
19357398 2009 Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia.
19084217 2009 Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels.
18976966 2008 The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin.
18603562 2008 A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron.
18449907 2008 Genetic upregulation of matriptase-2 reduces the aggressiveness of prostate cancer cells in vitro and in vivo and affects FAK and paxillin localisation.
18408718 2008 Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA).
17981570 2008 The type II transmembrane serine protease matriptase-2--identification, structural features, enzymology, expression pattern and potential roles.
17575220 2007 Matriptase-2 inhibits breast tumor growth and invasion and correlates with favorable prognosis for breast cancer patients.
16959974 2006 The consensus coding sequences of human breast and colorectal cancers.
16533768 2006 Refinement of the 22q12-q13 breast cancer--associated region: evidence of TMPRSS6 as a candidate gene in an eastern Finnish population.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15461802 2004 A genome annotation-driven approach to cloning the human ORFeome.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12975309 2003 The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.
12784999 Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12149247 2002 Matriptase-2, a membrane-bound mosaic serine proteinase predominantly expressed in human liver and showing degrading activity against extracellular matrix proteins.
10591208 1999 The DNA sequence of human chromosome 22.