Table 1 Human and mouse mutations that... | American Society of Hematology

Table 1

Human and mouse mutations that cause systemic iron dysregulation

Component	Putative role
Transferrin^34,35	Iron carrier, presents extracellular iron to hepatocytes for sensing
TfR1	Cellular iron uptake, signals holotransferrin concentration through HFE?
TfR2^36,37	Holotransferrin sensing, partially redundant to TfR1/HFE^38,39
HFE^40,41	Binds to TfR1⁴² and TfR2,⁴³ signals TfR1 occupancy⁴²
Hemojuvelin^44-46	BMP coreceptor,⁴⁷ enhances BMP signaling, target of TMPRSS6^48,49
Neogenin	Binds to hemojuvelin,^50,51 enhances BMP signaling^51,52
TMPRSS6	Negative regulator,^35,75 decreases BMP signaling by cleaving hemojuvelin^53-55
Smad4	Conveys BMP signal to the hepcidin transcription complex⁵⁶
BMP6	Iron-specific ligand^57,58 of the BMP receptor,⁵⁹ increased by hepatic iron⁶⁰

Component	Putative role
Transferrin^34,35	Iron carrier, presents extracellular iron to hepatocytes for sensing
TfR1	Cellular iron uptake, signals holotransferrin concentration through HFE?
TfR2^36,37	Holotransferrin sensing, partially redundant to TfR1/HFE^38,39
HFE^40,41	Binds to TfR1⁴² and TfR2,⁴³ signals TfR1 occupancy⁴²
Hemojuvelin^44-46	BMP coreceptor,⁴⁷ enhances BMP signaling, target of TMPRSS6^48,49
Neogenin	Binds to hemojuvelin,^50,51 enhances BMP signaling^51,52
TMPRSS6	Negative regulator,^35,75 decreases BMP signaling by cleaving hemojuvelin^53-55
Smad4	Conveys BMP signal to the hepcidin transcription complex⁵⁶
BMP6	Iron-specific ligand^57,58 of the BMP receptor,⁵⁹ increased by hepatic iron⁶⁰