Polycystic kidney disease 3 (autosomal dominant) is a protein that in humans is encoded by the PKD3 gene. [1]
Polycystic kidney disease (ADPKD) is a life threatening hereditary disorder; it is characterized by the development of fluid-filled cyst formation and expansion of the kidney and other organs. [2] It is an autosomal dominant disease, and it is the most common hereditary disorders with a rate of occurrence of approximately 1 in 1000. [3]
ADPKD is an autosomal dominant disease, it contains 3 types of mutation: PKD1 (16 Chr), PKD2 (4 Chr) PKD3 (11 Chr, this gene). Mutations in the 3 different genes PKD1, PKD2 and PKD3 cause a very similar disorder of the autosomal dominant form of polycystic kidney disease (ADPKD). [4] The PKD3 gene is located on chromosome number 11q12.3; the phenotype MIM number is 600666.
PKD3 it is the result of a mutation in the GANAB gene. The GANAB gene codes the catalytic alpha subunit of glucosidase II and noncatalytic beta subunit; the glycosyl hydrolase 31 families of proteins. The heterodimeric glucosidase II enzyme has an important function in protein folding and catalyzes the hydrolysis of glucose residues. In the endoplasmic reticulum, the quality control is done by cutting the residues of glucose from the immature glycoproteins. The rise in the expression of the protein leads to the lung tumor tissue. Also, any mutation in this gene causes autosomal dominant polycystic liver disease. [7]
PKD3 occurs in adults and it sometimes shows symptoms in children. It is known as 'polycystic kidneys'. Polycystic kidney disease (PKD3) is an autosomal dominant inheritance that leads to renal cysts. It is related to the liver cysts that sometimes causes organ dysfunction. It is usually detected in middle to late aged individuals developing severe cysts in kiddy and liver. However, the renal disease is mild and very few patients have hypertension, it does not happen regularly. Unlike the liver disease where it develops a wide spectrum of severity; some have no cyst, while others have severe liver involvement polycystic kidney disease. [2]
In an analysis of 20 patients from 9 unrelated families develop polycystic kidney disease with heterozygous mutations in the GANAB gene. 5 of the mutations from the GANAB gene were predicted to result in a short protein (frameshift, nonsense, or splicing), and 3 missense mutations. 7 of the families had a diagnosis of PKD, while the other 2 families had a diagnosis of polycystic liver disease (PCLD). Most of the patients developed during adulthood, except one showed symptoms at the age of 9. The recordings indicate that the renal disease was insignificant. Also, very few of them had high blood pressure. Renal imaging has also been done, which present variable numbers of multiple cysts (from less than 10 to more than 40).Those suffering from PCLD, some had no cyst while others develop severe disease, requiring surgery. Therefore, this shows that GANAB-related PKD and PCLD are not necessarily separate diseases, but there was significant phenotypic overlap between the 2, and that the PKD3 is responsible for this disease. [3]
There is no specific treatment for PKD3. However, a lot of research is going on to mimic the symptoms. Regular monitoring and following up on the complications can assist in maintaining the health and extend a person's life. Recent research shows that the treatment with protein kinase C (PKC) inhibitor may help to mimic the increase of PKD3, by RacV12 and aluminum fluoride.
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent, potentially lethal, monogenic human disorder. It is associated with large interfamilial and intrafamilial variability, which can be explained to a large extent by its genetic heterogeneity and modifier genes. It is also the most common of the inherited cystic kidney diseases — a group of disorders with related but distinct pathogenesis, characterized by the development of renal cysts and various extrarenal manifestations, which in case of ADPKD include cysts in other organs, such as the liver, seminal vesicles, pancreas, and arachnoid membrane, as well as other abnormalities, such as intracranial aneurysms and dolichoectasias, aortic root dilatation and aneurysms, mitral valve prolapse, and abdominal wall hernias. Over 50% of patients with ADPKD eventually develop end stage kidney disease and require dialysis or kidney transplantation. ADPKD is estimated to affect at least one in every 1000 individuals worldwide, making this disease the most common inherited kidney disorder with a diagnosed prevalence of 1:2000 and incidence of 1:3000-1:8000 in a global scale.
Chromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 4 spans more than 186 million base pairs and represents between 6 and 6.5 percent of the total DNA in cells.
Cystic kidney disease refers to a wide range of hereditary, developmental, and acquired conditions and with the inclusion of neoplasms with cystic changes, over 40 classifications and subtypes have been identified. Depending on the disease classification, the presentation may be at birth, or much later into adult life. Cystic disease may involve one or both kidneys and may, or may not, occur in the presence of other anomalies. A higher incidence of is found in males and prevalence increases with age. Renal cysts have been reported in more than 50% of patients over the age of 50. Typically, cysts grow up to 2.88 mm annually and may cause related pain and/or hemorrhage.
Medullary cystic kidney disease (MCKD) is an autosomal dominant kidney disorder characterized by tubulointerstitial sclerosis leading to end-stage renal disease. Because the presence of cysts is neither an early nor a typical diagnostic feature of the disease, and because at least 4 different gene mutations may give rise to the condition, the name autosomal dominant tubulointerstitial kidney disease (ADTKD) has been proposed, to be appended with the underlying genetic variant for a particular individual. Importantly, if cysts are found in the medullary collecting ducts they can result in a shrunken kidney, unlike that of polycystic kidney disease. There are two known forms of medullary cystic kidney disease, mucin-1 kidney disease 1 (MKD1) and mucin-2 kidney disease/uromodulin kidney disease (MKD2). A third form of the disease occurs due to mutations in the gene encoding renin (ADTKD-REN), and has formerly been known as familial juvenile hyperuricemic nephropathy type 2.
Phosphorylase kinase (PhK) is a serine/threonine-specific protein kinase which activates glycogen phosphorylase to release glucose-1-phosphate from glycogen. PhK phosphorylates glycogen phosphorylase at two serine residues, triggering a conformational shift which favors the more active glycogen phosphorylase “a” form over the less active glycogen phosphorylase b.
Polycystic liver disease (PLD) usually describes the presence of multiple cysts scattered throughout normal liver tissue. PLD is commonly seen in association with autosomal-dominant polycystic kidney disease, with a prevalence of 1 in 400 to 1000, and accounts for 8–10% of all cases of end stage renal disease. The much rarer autosomal-dominant polycystic liver disease will progress without any kidney involvement.
Fibrocystin is a large, receptor-like protein that is thought to be involved in the tubulogenesis and/or maintenance of duct-lumen architecture of epithelium. FPC associates with the primary cilia of epithelial cells and co-localizes with the Pkd2 gene product polycystin-2 (PC2), suggesting that these two proteins may function in a common molecular pathway.
Nephronophthisis is a genetic disorder of the kidneys which affects children. It is classified as a medullary cystic kidney disease. The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure. It is a form of ciliopathy. Its incidence has been estimated to be 0.9 cases per million people in the United States, and 1 in 50,000 births in Canada.
Polycystin 1 is a protein that in humans is encoded by the PKD1 gene. Mutations of PKD1 are associated with most cases of autosomal dominant polycystic kidney disease, a severe hereditary disorder of the kidneys characterised by the development of renal cysts and severe kidney dysfunction.
The catalytic subunit α of protein kinase A is a key regulatory enzyme that in humans is encoded by the PRKACA gene. This enzyme is responsible for phosphorylating other proteins and substrates, changing their activity. Protein kinase A catalytic subunit is a member of the AGC kinase family, and contributes to the control of cellular processes that include glucose metabolism, cell division, and contextual memory. PKA Cα is part of a larger protein complex that is responsible for controlling when and where proteins are phosphorylated. Defective regulation of PKA holoenzyme activity has been linked to the progression of cardiovascular disease, certain endocrine disorders and cancers.
cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR1A gene.
Polycystin-2 is a protein that in humans is encoded by the PKD2 gene.
Glucosidase 2 subunit beta is an enzyme that in humans is encoded by the PRKCSH gene.
Polycystic kidney disease 2-like 1 protein also known as transient receptor potential polycystic 2 is a protein that in humans is encoded by the PKD2L1 gene.
HCLS1-associated protein X-1 is a protein that in humans is encoded by the HAX1 gene.
Polycystic kidney disease is a genetic disorder in which the renal tubules become structurally abnormal, resulting in the development and growth of multiple cysts within the kidney. These cysts may begin to develop in utero, in infancy, in childhood, or in adulthood. Cysts are non-functioning tubules filled with fluid pumped into them, which range in size from microscopic to enormous, crushing adjacent normal tubules and eventually rendering them non-functional as well.
Autosomal recessive polycystic kidney disease (ARPKD) is the recessive form of polycystic kidney disease. It is associated with a group of congenital fibrocystic syndromes. Mutations in the PKHD1 cause ARPKD.
Glomerulocystic kidney disease (GCKD) is a cystic disorder of the kidneys. GCKD involves cystic dilation of Bowman's capsule. It can occur with or without congenital abnormality.
The Polycystin Cation Channel (PCC) Family consists of several transporters ranging in size from 500 to over 4000 amino acyl residues (aas) in length and exhibiting between 5 and 18 transmembrane segments (TMSs). This family is a constituent of the Voltage-Gated Ion Channel (VIC) Superfamily. These transporters generally catalyze the export of cations. A representative list of proteins belonging to the PCC family can be found in the Transporter Classification Database.
Protein kinase, X-linked is a protein that in humans is encoded by the PRKX gene.
[7] GANAB glucosidase II alpha subunit Homo sapiens (human). Gene ID:23193, 2016.