General information about the gene

– This gene encodes a kidney-specific sodium-potassium-chloride cotransporter

that is expressed on the luminal

– membrane of renal epithelial cells of the thick ascending limb of Henle's loop and
the macula densa. It plays a

– key role in concentrating urine and accounts for most of the NaCl resorption. It is
sensitive to such diuretics

– as furosemide and bumetanide. Some Bartter-like syndromes result from defects

in this gene. Alternative splicing

– results in multiple transcript variants encoding distinct isoforms. Additional splice

variants have been

– described but their biological validity in humans has not been experimentally
proven
Other names for this gene :

BSC1
- bumetanide-sensitive sodium-(potassium)-chloride
cotransporter 2
- kidney-specific Na-K-Cl symporter
- Na-K-2Cl cotransporter
- NKCC2
- S12A1_HUMAN
- solute carrier family 12 (sodium/potassium/chloride
transporter), member 1
- solute carrier family 12 (sodium/potassium/chloride
transporters), member 1
Data about the gene:

Locus : 15q21.1 , which is the long (q) arm of chromosome 15 at position 21.1
Nr.exons : 29
Genomic Locations for SLC12A1 Gene : chr15:48,191,664-48,304,078
(GRCh38/hg38
Size: 112,415 bases
Gene exeprission :
Molecular level :
Cellular level :
Organism level :
Mutations in slc12a1 gene:

More than 40 mutations in the SLC12A1 gene have been

identified in people with Bartter syndrome type I. This form of
the disorder is very severe, causing life-threatening health
problems that become apparent before or soon after birth.
Most of the SLC12A1 gene mutations responsible for Bartter
syndrome change single protein building blocks (amino acids) in
the NKCC2 protein. Other mutations delete amino acids from
the protein or lead to the production of an abnormally short
version of the NKCC2 protein. Each of the known mutations
prevents the NKCC2 protein from transporting ions into kidney
cells. As a result, the kidneys cannot reabsorb salt normally and
excess salt is lost through the urine (salt wasting). The abnormal
salt loss disrupts the normal balance of sodium, potassium, and
other ions in the body. These imbalances underlie the major
features of Bartter syndrome.
Bartter syndrome:

Bartter syndrome is a group of very similar kidney disorders that cause

an imbalance of potassium, sodium, chloride, and related molecules in
the body.
In some cases, Bartter syndrome becomes apparent before birth. The
disorder can cause polyhydramnios, which is an increased volume of fluid
surrounding the fetus (amniotic fluid). Polyhydramnios increases the risk
of premature birth.
Beginning in infancy, affected individuals often fail to grow and gain
weight at the expected rate (failure to thrive). They lose excess amounts
of salt (sodium chloride) in their urine, which leads to dehydration,
constipation, and increased urine production (polyuria). In addition, large
amounts of calcium are lost through the urine (hypercalciuria), which can
cause weakening of the bones (osteopenia). Some of the calcium is
deposited in the kidneys as they are concentrating urine, leading to
hardening of the kidney tissue (nephrocalcinosis). Bartter syndrome is
also characterized by low levels of potassium in the blood (hypokalemia),
which can result in muscle weakness, cramping, and fatigue. Rarely,
affected children develop hearing loss caused by abnormalities in the
inner ear (sensorineural deafness).
Two major forms of Bartter syndrome are distinguished by their age of onset and
severity. One form begins before birth (antenatal) and is often life-threatening. The
other form, often called the classical form, begins in early childhood and tends to be
less severe. Once the genetic causes of Bartter syndrome were identified,
researchers also split the disorder into different types based on the genes involved.
Types I, II, and IV have the features of antenatal Bartter syndrome. Because type IV
is also associated with hearing loss, it is sometimes called antenatal Bartter
syndrome with sensorineural deafness. Type III usually has the features of

classical Bartter syndrome.

Treatment for bartter syndrome :

Since first described in 1962, several types of medical treatment have

been used, including the following:

1) Sodium and potassium supplements - Used for the electrolyte

imbalances
2) Aldosterone antagonists and diuretic spironolactone - Are mainstays of
therapy
3) Angiotensin-converting enzyme (ACE) inhibitors - Used to counteract
the effects of angiotensin II (ANG II) and aldosterone
4) Indomethacin - Used to decrease prostaglandin excretion
5) Growth hormone (GH) - Used to treat short stature
6) Calcium or magnesium supplements - May occasionally be needed if
tetany or muscle spasms are present