renal tubular dysgenesis At least six mutations in the AGT gene have been found to cause a severe kidney disorder called renal tubular dysgenesis. This condition is characterized by abnormal kidney development before birth, the inability to produce urine (anuria), and severe low blood pressure (hypotension). These problems result in a reduction of amniotic fluid (oligohydramnios), which leads to a set of birth defects known as the Potter sequence. Renal tubular dysgenesis can be caused by mutations in both copies of any of the genes involved in the renin-angiotensin system. Most of the mutations in the AGT gene that cause this disorder change single protein building blocks (amino acids) in the angiotensinogen protein. These changes occur in a region of the protein that is necessary for its conversion to angiotensin I. It is thought that the altered angiotensinogen cannot be converted, leading to a nonfunctional renin-angiotensin system. Without this system, the kidneys cannot control blood pressure. Because of low blood pressure, the flow of blood is reduced (hypoperfusion), and the body does not get enough oxygen during fetal development. As a result, kidney development is impaired, leading to the features of renal tubular dysgenesis. other disorders Variations in the AGT gene are associated with susceptibility to a form of high blood pressure (hypertension) called essential hypertension. Essential hypertension is a complex disorder associated with many genetic and environmental factors. The AGT gene variations associated with this condition affect single DNA building blocks (nucleotides) and likely lead to higher levels of the angiotensinogen protein.

     The AGT gene provides instructions for making a protein called angiotensinogen. This protein is part of the renin-angiotensin system, which regulates blood pressure and the balance of fluids and salts in the body. In the first step of this process, angiotensinogen is converted to angiotensin I. Through an additional step, angiotensin I is converted to angiotensin II. Angiotensin II causes blood vessels to narrow (constrict), which results in increased blood pressure. This molecule also stimulates production of the hormone aldosterone, which triggers the absorption of salt and water by the kidneys. The increased amount of fluid in the body also increases blood pressure. Proper blood pressure during fetal growth, which delivers oxygen to the developing tissues, is required for normal development of the kidneys, particularly of structures called the proximal tubules, and other tissues. In addition, angiotensin II may play a more direct role in kidney development, perhaps by affecting growth factors involved in the development of kidney structures.

The following transcription factors affect gene expression:

• PPAR-gamma1
• PPAR-gamma2
• p53
• STAT3
• NF-kappaB1
• C/EBPalpha
• Sp1
• STAT1
• STAT1alpha
• p300

Tissue specificity:

Expressed by the liver and secreted in plasma.

Caution:

It is uncertain whether Met-1 or Met-10 is the initiator.

Molecular Function:

• Serine-Type Endopeptidase Inhibitor Activity
• Hormone Activity
• Growth Factor Activity
• Superoxide-Generating Nadph Oxidase Activator Activity
• Sodium Channel Regulator Activity
• Type 1 Angiotensin Receptor Binding
• Type 2 Angiotensin Receptor Binding
• Receptor Agonist Activity

Biological Processes:

• Regulation Of Cell Growth
• Positive Regulation Of Cytokine Production
• Kidney Development
• Blood Vessel Remodeling
• Angiotensin Maturation
• Regulation Of Blood Volume By Renin-Angiotensin
• Renin-Angiotensin Regulation Of Aldosterone Production
• Regulation Of Renal Output By Angiotensin
• Regulation Of Heart Rate
• Regulation Of Blood Vessel Diameter By Renin-Angiotensin
• Renal System Process
• Angiotensin-Mediated Drinking Behavior
• Positive Regulation Of Extracellular Matrix Constituent Secretion
• Cellular Sodium Ion Homeostasis
• Cell Surface Receptor Signaling Pathway
• G-Protein Coupled Receptor Signaling Pathway
• G-Protein Coupled Receptor Signaling Pathway Coupled To Cgmp Nucleotide Second Messenger
• Phospholipase C-Activating G-Protein Coupled Receptor Signaling Pathway
• Activation Of Phospholipase C Activity
• Positive Regulation Of Cytosolic Calcium Ion Concentration
• Nitric Oxide Mediated Signal Transduction
• Cell-Cell Signaling
• Female Pregnancy
• Aging
• Regulation Of Blood Pressure
• Positive Regulation Of Activation Of Jak2 Kinase Activity
• Positive Regulation Of Endothelial Cell Migration
• Positive Regulation Of Cardiac Muscle Hypertrophy
• Negative Regulation Of Gene Expression
• Positive Regulation Of Cardiac Muscle Cell Apoptotic Process
• Positive Regulation Of Macrophage Derived Foam Cell Differentiation
• Positive Regulation Of Cholesterol Esterification
• Regulation Of Norepinephrine Secretion
• Positive Regulation Of Phosphatidylinositol 3-Kinase Signaling
• Artery Smooth Muscle Contraction
• Response To Muscle Activity Involved In Regulation Of Muscle Adaptation
• Negative Regulation Of Angiogenesis
• Regulation Of Vasoconstriction
• Negative Regulation Of Cell Growth
• Positive Regulation Of Cellular Protein Metabolic Process
• Positive Regulation Of Superoxide Anion Generation
• Positive Regulation Of Nad(P)H Oxidase Activity
• Negative Regulation Of Tissue Remodeling
• Low-Density Lipoprotein Particle Remodeling
• Catenin Import Into Nucleus
• Regulation Of Renal Sodium Excretion
• Positive Regulation Of Renal Sodium Excretion
• Angiotensin-Activated Signaling Pathway
• Regulation Of Cell Proliferation
• Vasodilation
• Positive Regulation Of Nitric Oxide Biosynthetic Process
• Positive Regulation Of Epidermal Growth Factor Receptor Signaling Pathway
• Positive Regulation Of Blood Pressure
• Positive Regulation Of Transcription, Dna-Templated
• Positive Regulation Of Vasodilation
• Fibroblast Proliferation
• Positive Regulation Of Fibroblast Proliferation
• Regulation Of Long-Term Neuronal Synaptic Plasticity
• Smooth Muscle Cell Proliferation
• Cytokine Secretion
• Positive Regulation Of Inflammatory Response
• Positive Regulation Of Peptidyl-Tyrosine Phosphorylation
• Positive Regulation Of Nf-Kappab Transcription Factor Activity
• Negative Regulation Of Neurotrophin Trk Receptor Signaling Pathway
• Stress-Activated Mapk Cascade
• Regulation Of Calcium Ion Transport
• Regulation Of Transmission Of Nerve Impulse
• Cell Growth Involved In Cardiac Muscle Cell Development
• Positive Regulation Of Protein Tyrosine Kinase Activity
• Erk1 And Erk2 Cascade
• Uterine Smooth Muscle Contraction
• Cellular Response To Mechanical Stimulus
• Positive Regulation Of Branching Involved In Ureteric Bud Morphogenesis
• Regulation Of Extracellular Matrix Assembly
• Positive Regulation Of Membrane Hyperpolarization
• Positive Regulation Of L-Arginine Import Into Cell
• Positive Regulation Of Gap Junction Assembly
• Regulation Of Cardiac Conduction
• Positive Regulation Of Vascular Smooth Muscle Cell Proliferation
• Positive Regulation Of Vascular Associated Smooth Muscle Cell Migration
• Positive Regulation Of L-Lysine Import Into Cell
• Positive Regulation Of Reactive Oxygen Species Metabolic Process
• Negative Regulation Of Sodium Ion Transmembrane Transporter Activity
• Positive Regulation Of Extrinsic Apoptotic Signaling Pathway
• Positive Regulation Of Glucose Import In Response To Insulin Stimulus