|
Renal tubular acidosis
|
0.540 |
GeneticVariation
|
phenotype |
BEFREE |
Mutations in the gene SLC4A4, encoding Na+-HCO3- cotransporter (NBC-1), have been found in proximal RTA with ocular abnormalities; in the gene SLC4A1, encoding Cl(-)-HCO3- exchanger (AE1), in autosomal dominant distal RTA; in the gene ATP6B1, encoding B1 subunit of H+-ATPase, in autosomal recessive distal RTA with sensorineural deafness; and in the gene CA2, encoding carbonic anhydrase II, in autosomal recessive osteopetrosis.
|
11045400 |
2000 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
NBCe1-A transmembrane segment 1 (TM1) is involved in forming part of the ion permeation pathway, and a missense mutation S427L in TM1 impairs ion transport, causing proximal renal tubular acidosis.
|
23362273 |
2013 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
This is the first report of congenital proximal renal tubular acidosis carrying compound heterozygous SLC4A4 mutations in exon-intron boundary regions.
|
29914390 |
2018 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
Biomarker
|
disease |
BEFREE |
These results have implications for understanding the role of kNBC1 in the pathophysiologic processes of pRTA associated with ocular abnormalities and mental retardation.
|
11274232 |
2001 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
Biomarker
|
disease |
BEFREE |
Given the important role of proximal tubule transepithelial bicarbonate absorption in systemic acid-base balance, a clear understanding of the structure-functional properties of NBCe1 is a prerequisite for elucidating the mechanisms of defective transepithelial bicarbonate transport in pRTA.
|
23917030 |
2013 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Proximal renal tubular acidosis (pRTA) is a rare, recessively-inherited disease characterized by abnormally acidic blood, blindness, as well as below average height and weight. pRTA is typically associated with homozygous mutation of the solute carrier 4 family gene SLC4A4.
|
27338124 |
2016 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Alkali therapy remains the preferred treatment for pRTA, but it is unclear which nonrenal signs are secondary to acidemia and which are a direct consequence of NBCe1 loss from nonrenal sites (such as the eye and enamel organ) and therefore require separate therapy.
|
31040187 |
2019 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Mutations in Na(+)-HCO(3)(-) cotransporter (NBC-1) cause proximal renal tubular acidosis (pRTA) associated with ocular abnormalities.
|
12444017 |
2003 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Mutations in NBCe1 cause proximal renal tubular acidosis (pRTA) with neurologic and ophthalmologic extrarenal manifestations.
|
24515290 |
2014 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
In patients, NBCe1-A-T485S is predicted to transport Na(+)-HCO3(-) in the reverse direction from blood into proximal tubule cells thereby impairing transepithelial HCO3(-) absorption, possibly representing a new pathogenic mechanism for generating human pRTA.
|
23636456 |
2013 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
These findings represent the first evidence that in the presence of the NBCe1-A-Q29X mutation that causes proximal renal tubular acidosis, full-length functional NBCe1-A protein can be produced.
|
18614622 |
2008 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We have identified and functionally characterized a novel, homozygous, missense mutation (S427L) in NBCe1, also resulting in pRTA and similar eye defects without mental retardation.
|
15471865 |
2004 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Our results expand the spectrum of kNBC1 mutations in permanent isolated pRTA with ocular abnormalities and increase our understanding of the renal tubular mechanism that is essential for acid-base homeostasis.
|
15085340 |
2004 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Mutations in the kidney type Na+/HCO3- cotransporter gene (SLC4A4) cause permanent isolated proximal RTA with ocular abnormalities.
|
12027212 |
2002 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
This study identified a new homozygous NBC1 mutation (G486R) in a patient with severe pRTA.
|
17661077 |
2008 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Though rare, recessive SLC4A4 mutations have been reported in patients with proximal renal tubular acidosis, short stature, and ocular pathology.
|
16636648 |
2006 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Patients with autosomal recessive pRTA and ocular abnormalities have recently been found to have mutations in the kidney type Na(+)/HCO(3)(-) cotransporter gene (SLC4A4).
|
12138151 |
2002 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
Biomarker
|
disease |
BEFREE |
Slc4a4-null mice are a model of proximal renal tubular acidosis (pRTA).
|
24828138 |
2014 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
Biomarker
|
disease |
BEFREE |
In the proximal tubule, mutations of solute carrier 4A4 (SLC4A4) (electrogenic Na<sup>+</sup>/HCO<sub>3</sub><sup>-</sup>-cotransporter Na<sup>+</sup>/bicarbonate cotransporter e1 [NBCe1]) and other genes such as CLCN5 (Cl<sup>-</sup>/H<sup>+</sup>-antiporter), SLC2A2 (GLUT2 glucose transporter), or EHHADH (enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase) causing more generalized proximal tubule dysfunction can cause proximal renal tubular acidosis resulting from bicarbonate wasting and reduced ammoniagenesis.
|
31300090 |
2019 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
Biomarker
|
disease |
BEFREE |
Mutations in the gene encoding the Na+/HCO3- cotransporter, NBC1, have recently been identified in proximal renal tubular acidosis with corneal calcification.
|
10990375 |
2000 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
These results, together with the presence of nonfunctional mutants (Q29X and DeltaA) in other patients, suggest that at least approximately 50% reduction of NBC1 activity would be required to cause severe pRTA.
|
15930088 |
2005 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Homozygous mutations in SLC4A4, encoding the electrogenic Na(+)-HCO(3)(-) cotransporter NBCe1, have been known to cause proximal renal tubular acidosis (pRTA) and ocular abnormalities.
|
20798035 |
2010 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Recently, a novel homozygous missense mutant (R881C) of NBCe1-A was reported from a patient with a severe pRTA phenotype.
|
16707554 |
2006 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Thus, NBC1(W516X/W516X) mice with pRTA represent an animal model for metabolic acidosis and may be useful for testing therapeutic inhibition of NMD in vivo.
|
21228764 |
2011 |
|
Renal Tubular Acidosis, Type II
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
A 3D homology model predicts that Gln913 is located in the gating domain of NBCe1 and neighbours the 3D space occupied by another pRTA-associated residue (Arg881), highlighting an important and conformationally-sensitive region of NBCe1.
|
29449648 |
2018 |