GTLMNS
MCID: GTL001
MIFTS: 65

Gitelman Syndrome (GTLMNS)

Categories: Blood diseases, Genetic diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Gitelman Syndrome

MalaCards integrated aliases for Gitelman Syndrome:

Name: Gitelman Syndrome 57 12 74 20 43 58 73 36 13 54 44 15 71
Familial Hypokalemia-Hypomagnesemia 20 43 29 6
Hypomagnesemia-Hypokalemia, Primary Renotubular, with Hypocalciuria 57 12 20
Potassium and Magnesium Depletion 57 20 73
Gitelman's Syndrome 20 43
Gtlmns 57 73
Hypokalemia-Hypomagnesemia, Primary Renotubular, with Hypocalciuria 43
Primary Renal Tubular Hypokalemic Hypomagnesemia with Hypocalciuria 58
Primary Renotubular Hypomagnesemia-Hypokalemia with Hypocalciuria 73
Tubular Hypomagnesemia-Hypokalemia with Hypocalcuria 43
Bartter Syndrome Hypocalciuric Variant 73
Bartter Syndrome Gitelman Variant 73
Syndrome, Gitelman 39
Gs 43

Characteristics:

Orphanet epidemiological data:

58
gitelman syndrome
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in childhood (later than in antenatal bartter syndrome )
prevalence of 19 in 1,000,000 in sweden
prevalence of 1 in 40,000 among caucasians
heterozygous carriers have decreased blood pressure compared to the general population


HPO:

31
gitelman syndrome:
Inheritance autosomal recessive inheritance
Onset and clinical course juvenile onset


Classifications:

Orphanet: 58  
Rare renal diseases


Summaries for Gitelman Syndrome

MedlinePlus Genetics : 43 Gitelman syndrome is a kidney disorder that causes an imbalance of charged atoms (ions) in the body, including ions of potassium, magnesium, and calcium.The signs and symptoms of Gitelman syndrome usually appear in late childhood or adolescence. Common features of this condition include painful muscle spasms (tetany), muscle weakness or cramping, dizziness, and salt craving. Also common is a tingling or prickly sensation in the skin (paresthesias), most often affecting the face. Some individuals with Gitelman syndrome experience excessive tiredness (fatigue), low blood pressure, and a painful joint condition called chondrocalcinosis. Studies suggest that Gitelman syndrome may also increase the risk of a potentially dangerous abnormal heart rhythm called ventricular arrhythmia.The signs and symptoms of Gitelman syndrome vary widely, even among affected members of the same family. Most people with this condition have relatively mild symptoms, although affected individuals with severe muscle cramping, paralysis, and slow growth have been reported.

MalaCards based summary : Gitelman Syndrome, also known as familial hypokalemia-hypomagnesemia, is related to primary hypomagnesemia and chondrocalcinosis, and has symptoms including seizures, polydipsia and generalized muscle weakness. An important gene associated with Gitelman Syndrome is SLC12A3 (Solute Carrier Family 12 Member 3), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Ion channel transport. The drugs Mifepristone and Progesterone have been mentioned in the context of this disorder. Affiliated tissues include Kidney, pancreas and bone, and related phenotypes are hypokalemia and failure to thrive

Disease Ontology : 12 A renal tubular transport disease that is has material basis in mutations in genes that produce proteins involved in the kidneys' reabsorption of salt (sodium chloride or NaCl) from urine back into the bloodstream, thus impairing the kidneys' ability to reabsorb salt, leading to the loss of excess salt in the urine (salt wasting).

GARD : 20 Gitelman syndrome is a kidney function disorder that causes an imbalance of charged atoms (ions) in the body, including ions of potassium, magnesium, and calcium. It is usually diagnosed during late childhood or adulthood. More common symptoms include fatigue, salt craving, thirst, frequent urination, muscle cramping, muscle weakness, dizziness, tingling or numbness, low blood pressure, and heart palpitations. Gitelman syndrome can be caused by changes (mutations) in the SLC12A3 or CLCNKB genes and is inherited in an autosomal recessive manner. Treatment may include supplementation of potassium and magnesium, and a high sodium and high potassium diet.

OMIM® : 57 Gitelman syndrome is an autosomal recessive renal tubular salt-wasting disorder characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. It is the most common renal tubular disorder among Caucasians (prevalence of 1 in 40,000). Most patients have onset of symptoms as adults, but some can present in childhood. Clinical features include transient periods of muscle weakness and tetany, abdominal pains, and chondrocalcinosis (summary by Glaudemans et al., 2012). Gitelman syndrome is sometimes referred to as a mild variant of classic Bartter syndrome (607364). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364. (263800) (Updated 05-Mar-2021)

KEGG : 36 Gitelman syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria and is caused by mutations in the thiazide-sensitive sodium chloride transporter.

UniProtKB/Swiss-Prot : 73 Gitelman syndrome: An autosomal recessive disorder characterized by hypokalemic alkalosis in combination with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. Patients are often asymptomatic or present transient periods of muscular weakness and tetany, usually accompanied by abdominal pain, vomiting and fever. The phenotype is highly heterogeneous in terms of age at onset and severity. Cardinal features such as hypocalciuria and hypomagnesemia might also change during the life cycle of a given patient. It has overlapping features with Bartter syndrome.

Wikipedia : 74 Gitelman syndrome (GS) is an autosomal recessive kidney tubule disorder characterized by low blood... more...

Related Diseases for Gitelman Syndrome

Diseases related to Gitelman Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 188)
# Related Disease Score Top Affiliating Genes
1 primary hypomagnesemia 31.4 TRPM6 SLC12A1 KCNJ1 CLDN16
2 chondrocalcinosis 30.8 SLC12A3 REN CASR
3 hypokalemia 30.8 SLC12A3 SLC12A1 REN KCNJ10 KCNJ1 CLCNKB
4 bartter syndrome, type 3 30.6 TRPM6 SLC12A3 SLC12A1 REN KCNJ1 CLDN16
5 bartter syndrome, type 4b, neonatal, with sensorineural deafness 30.2 CLCNKB CLCNKA
6 bartter syndrome, type 4a, neonatal, with sensorineural deafness 30.1 KCNJ1 CLCNKB BSND
7 bartter syndrome, type 2, antenatal 30.1 SLC12A1 KCNJ1 CASR
8 renal hypertension 30.1 SLC12A3 REN AGT
9 antenatal bartter syndrome 30.0 SLC12A1 REN KCNJ1 BSND
10 diabetes insipidus 29.9 SLC12A1 REN CLCNKB CLCNKA
11 polyhydramnios 29.9 SLC12A3 SLC12A1 KCNJ1 CLCNKB BSND
12 nephrolithiasis, calcium oxalate 29.8 SLC12A1 CLDN16 CASR
13 metabolic acidosis 29.8 WNK4 WNK1 KLHL3
14 kidney disease 29.7 SLC12A3 SLC12A1 REN CASR AGT
15 nephrocalcinosis 29.6 SLC12A3 SLC12A1 KCNJ1 CLDN16 CLCNKB CASR
16 bartter syndrome, type 1, antenatal 29.6 SLC12A3 SLC12A1 KCNJ1 CLDN16 CASR
17 hypocalcemia, autosomal dominant 1 29.5 TRPM6 CLDN16 CLCNKB CASR BSND
18 nephrolithiasis 29.4 SLC12A1 KCNJ1 CLDN16 CLCNKB CASR BSND
19 diabetes insipidus, nephrogenic, autosomal 29.3 SLC12A3 SLC12A1 REN KCNJ1 CLCNKB CLCNKA
20 dent disease 1 29.2 SLC12A1 KCNJ1 CLDN16 CLCNKB CLCNKA CASR
21 liddle syndrome 1 28.4 WNK4 WNK3 WNK1 STK39 SLC12A3 SLC12A1
22 bartter disease 28.1 WNK4 WNK3 WNK1 TRPM6 STK39 STK24
23 hypertension, essential 28.1 WNK4 WNK3 WNK1 STK39 STK24 SLC12A3
24 hypomagnesemia 2, renal 11.0
25 pseudohypoaldosteronism, type i, autosomal recessive 11.0
26 conn's syndrome 10.5
27 autosomal recessive disease 10.5
28 graves' disease 10.3
29 orofaciodigital syndrome x 10.3 CLCNKA BSND
30 potter's syndrome 10.3 REN AGT
31 fibromuscular dysplasia 10.2 REN AGT
32 periodic paralysis 10.2
33 renal artery disease 10.2 REN AGT
34 malignant secondary hypertension 10.2 REN AGT
35 infantile bartter syndrome with sensorineural deafness 10.2 CLCNKB CLCNKA BSND
36 apparent mineralocorticoid excess 10.2 WNK4 REN KCNJ1
37 placenta disease 10.2 SLC12A1 REN KCNJ1
38 idiopathic hypercalciuria 10.2 REN CASR
39 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 10.1
40 proteinuria, chronic benign 10.1
41 diarrhea 10.1
42 hypomagnesemia 4, renal 10.1 WNK3 TRPM6
43 agenesis of the corpus callosum with peripheral neuropathy 10.1 WNK3 STK39 SLC12A1
44 neuropathy, hereditary sensory and autonomic, type iib 10.1 WNK1 STK39
45 atrial standstill 1 10.1
46 autoimmune disease 10.1
47 type 2 diabetes mellitus 10.1
48 hypophosphatemia 10.1
49 focal segmental glomerulosclerosis 10.1
50 hyperparathyroidism 10.1

Graphical network of the top 20 diseases related to Gitelman Syndrome:



Diseases related to Gitelman Syndrome

Symptoms & Phenotypes for Gitelman Syndrome

Human phenotypes related to Gitelman Syndrome:

58 31 (show top 50) (show all 84)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypokalemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002900
2 failure to thrive 58 31 very rare (1%) Frequent (79-30%) HP:0001508
3 muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0001324
4 prolonged qt interval 58 31 frequent (33%) Frequent (79-30%) HP:0001657
5 abdominal pain 58 31 occasional (7.5%) Frequent (79-30%) HP:0002027
6 hypomagnesemia 58 31 frequent (33%) Frequent (79-30%) HP:0002917
7 low-to-normal blood pressure 58 31 frequent (33%) Frequent (79-30%) HP:0002632
8 nausea and vomiting 58 31 occasional (7.5%) Occasional (29-5%) HP:0002017
9 proteinuria 58 31 occasional (7.5%) Occasional (29-5%) HP:0000093
10 delayed puberty 58 31 occasional (7.5%) Occasional (29-5%) HP:0000823
11 hypocalcemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002901
12 insulin resistance 58 31 occasional (7.5%) Occasional (29-5%) HP:0000855
13 muscle spasm 58 31 occasional (7.5%) Occasional (29-5%) HP:0003394
14 enuresis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000805
15 hypermagnesemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002918
16 nocturia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000017
17 metabolic alkalosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0200114
18 salt craving 58 31 occasional (7.5%) Occasional (29-5%) HP:0030083
19 renal potassium wasting 58 31 occasional (7.5%) Occasional (29-5%) HP:0000128
20 hyperhidrosis 58 31 very rare (1%) Very rare (<4-1%) HP:0000975
21 constipation 58 31 very rare (1%) Very rare (<4-1%) HP:0002019
22 cerebral calcification 58 31 very rare (1%) Very rare (<4-1%) HP:0002514
23 type ii diabetes mellitus 58 31 very rare (1%) Very rare (<4-1%) HP:0005978
24 polydipsia 58 31 very rare (1%) Very rare (<4-1%) HP:0001959
25 type i diabetes mellitus 58 31 very rare (1%) Very rare (<4-1%) HP:0100651
26 hashimoto thyroiditis 58 31 very rare (1%) Very rare (<4-1%) HP:0000872
27 vertigo 58 31 very rare (1%) Very rare (<4-1%) HP:0002321
28 arthralgia 58 31 very rare (1%) Very rare (<4-1%) HP:0002829
29 myalgia 58 31 very rare (1%) Very rare (<4-1%) HP:0003326
30 paresthesia 58 31 very rare (1%) Very rare (<4-1%) HP:0003401
31 varicose veins 58 31 very rare (1%) Very rare (<4-1%) HP:0002619
32 insomnia 58 31 very rare (1%) Very rare (<4-1%) HP:0100785
33 headache 58 31 very rare (1%) Very rare (<4-1%) HP:0002315
34 gout 58 31 very rare (1%) Very rare (<4-1%) HP:0001997
35 chondrocalcinosis 58 31 very rare (1%) Very rare (<4-1%) HP:0000934
36 syncope 58 31 very rare (1%) Very rare (<4-1%) HP:0001279
37 maternal diabetes 58 31 very rare (1%) Very rare (<4-1%) HP:0009800
38 neoplasm of the pancreas 58 31 very rare (1%) Very rare (<4-1%) HP:0002894
39 respiratory distress 58 31 very rare (1%) Very rare (<4-1%) HP:0002098
40 diarrhea 58 31 very rare (1%) Very rare (<4-1%) HP:0002014
41 tinnitus 58 31 very rare (1%) Very rare (<4-1%) HP:0000360
42 paralysis 58 31 very rare (1%) Very rare (<4-1%) HP:0003470
43 tubulointerstitial nephritis 58 31 very rare (1%) Very rare (<4-1%) HP:0001970
44 pericardial effusion 58 31 very rare (1%) Very rare (<4-1%) HP:0001698
45 raynaud phenomenon 58 31 very rare (1%) Very rare (<4-1%) HP:0030880
46 urinary incontinence 58 31 very rare (1%) Very rare (<4-1%) HP:0000020
47 abnormal t-wave 58 31 very rare (1%) Very rare (<4-1%) HP:0005135
48 scleroderma 58 31 very rare (1%) Very rare (<4-1%) HP:0100324
49 blurred vision 58 31 very rare (1%) Very rare (<4-1%) HP:0000622
50 graves disease 58 31 very rare (1%) Very rare (<4-1%) HP:0100647

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
seizures
paresthesias
paralysis, episodic, after strenuous exercise

Laboratory Abnormalities:
hypokalemia
hypocalciuria
hypomagnesemia

Skeletal:
chondrocalcinosis

Abdomen:
abdominal pain (in some patients)

Metabolic Features:
polydipsia
hypokalemic alkalosis

Muscle Soft Tissue:
tetany
generalized muscle weakness
muscle cramps

Genitourinary Kidneys:
renal potassium wasting
renal magnesium wasting
polyuria

Endocrine Features:
increased plasma renin

Clinical features from OMIM®:

263800 (Updated 05-Mar-2021)

UMLS symptoms related to Gitelman Syndrome:


seizures, polydipsia, generalized muscle weakness, muscle cramp, polyuria

GenomeRNAi Phenotypes related to Gitelman Syndrome according to GeneCards Suite gene sharing:

26 (show all 12)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00107-A-1 10.19 STK39
2 Decreased viability GR00221-A-1 10.19 STK24 TRPM6 WNK3 WNK4
3 Decreased viability GR00221-A-2 10.19 STK24 STK39 TRPM6 WNK3 WNK4
4 Decreased viability GR00221-A-3 10.19 WNK1
5 Decreased viability GR00221-A-4 10.19 STK24 TRPM6 WNK3 WNK4 WNK1
6 Decreased viability GR00240-S-1 10.19 STK39
7 Decreased viability GR00249-S 10.19 STK39 WNK1
8 Decreased viability GR00301-A 10.19 STK39
9 Decreased viability GR00386-A-1 10.19 WNK1
10 Decreased viability GR00402-S-2 10.19 WNK1
11 Decreased cell viability after pRB stimulation GR00230-A-1 9.16 STK39 WNK4
12 Increased senescence-associated beta-galactosidase protein expression after pRB stimulation GR00230-A-2 8.32 WNK4

MGI Mouse Phenotypes related to Gitelman Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.03 AGT BSND CLCNKA KCNJ1 KLHL3 REN
2 hematopoietic system MP:0005397 9.93 BSND CASR CLCNKA KCNJ1 KCNJ10 KLHL3
3 homeostasis/metabolism MP:0005376 9.91 AGT BSND CASR CLCNKA CLCNKB CLDN16
4 renal/urinary system MP:0005367 9.55 AGT BSND CASR CLCNKA CLCNKB CLDN16

Drugs & Therapeutics for Gitelman Syndrome

Drugs for Gitelman Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Mifepristone Approved, Investigational Phase 4 84371-65-3 55245
2
Progesterone Approved, Vet_approved Phase 4 57-83-0 5994
3
Eplerenone Approved Phase 1, Phase 2 107724-20-9 150310 443872
4
Amiloride Approved Phase 1, Phase 2 2016-88-8, 2609-46-3 16231
5
Omeprazole Approved, Investigational, Vet_approved Phase 1, Phase 2 73590-58-6 4594
6
Indomethacin Approved, Investigational Phase 1, Phase 2 53-86-1 3715
7 diuretics Phase 1, Phase 2
8 Diuretics, Potassium Sparing Phase 1, Phase 2
9 Sodium Channel Blockers Phase 1, Phase 2
10
Hydrochlorothiazide Approved, Vet_approved 58-93-5 3639
11 Sodium Chloride Symporter Inhibitors
12 Antihypertensive Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Monocentric STUDY, Randomised Double Blinded (Healthy Subjects, or Transversal (Patients With Gitelman Syndrome) Completed NCT02297048 Phase 4
2 Evaluation of Safety and Efficacity of Indometacin and Two Potassium Sparing Diuretics in Adult Patients Affected by Gitelman Syndrome Completed NCT01146197 Phase 1, Phase 2 TREATMENT
3 A Translational Approach to Gitelman Syndrome Completed NCT00822107 Hydrochlorothiazide
4 Clinical Significance of Heterozygosity for Mutations of the SLC12A3 Gene Coding for the Thiazide Sensitive Na-Cl Cotransporter Completed NCT02035046

Search NIH Clinical Center for Gitelman Syndrome

Cochrane evidence based reviews: gitelman syndrome

Genetic Tests for Gitelman Syndrome

Genetic tests related to Gitelman Syndrome:

# Genetic test Affiliating Genes
1 Familial Hypokalemia-Hypomagnesemia 29 SLC12A3

Anatomical Context for Gitelman Syndrome

MalaCards organs/tissues related to Gitelman Syndrome:

40
Kidney, Pancreas, Bone, Thyroid, Brain, Spinal Cord, Heart
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Gitelman Syndrome:
# Tissue Anatomical CompartmentCell Relevance
1 Kidney Distal Tubule Distal Tubule Cells Affected by disease, potential therapeutic candidate

Publications for Gitelman Syndrome

Articles related to Gitelman Syndrome:

(show top 50) (show all 489)
# Title Authors PMID Year
1
Hypokalemic paralysis due to Gitelman syndrome: a family study. 57 6 61
17000984 2006
2
Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. 6 54 57
8528245 1996
3
Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome. 57 61
22009145 2012
4
Generation and analysis of the thiazide-sensitive Na+ -Cl- cotransporter (Ncc/Slc12a3) Ser707X knockin mouse as a model of Gitelman syndrome. 57 61
20848653 2010
5
Mutations in the chloride channel gene, CLCNKB, leading to a mixed Bartter-Gitelman phenotype. 57 61
11102542 2000
6
Association of a mutation in thiazide-sensitive Na-Cl cotransporter with familial Gitelman's syndrome. 6 54
8954067 1996
7
Familial hypokalemia-hypomagnesemia or Gitelman's syndrome: a further case. 61 57
1436349 1992
8
Phosphorylation regulates NCC stability and transporter activity in vivo. 6
23833262 2013
9
Gitelman syndrome: pathophysiological and clinical aspects. 61 20
20650971 2010
10
Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure. 57
17981812 2008
11
Gitelman's not-so-benign syndrome. 57
16120871 2005
12
A case of Gitelman's syndrome with chondrocalcinosis. 57
9700481 1998
13
Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney. 57
8021284 1994
14
Primary structure and functional expression of a cDNA encoding the thiazide-sensitive, electroneutral sodium-chloride cotransporter. 57
8464884 1993
15
Familial hypokalaemia and hypomagnesaemia. A further family. 57
945655 1976
16
A new familial disorder characterized by hypokalemia and hypomagnesemia. 57
5929460 1966
17
Low potassium syndrome due to defective renal tubular mechanisms for handling potassium. 57
14877834 1951
18
Gitelman's syndrome with vomiting manifested by severe metabolic alkalosis and progressive renal insufficiency. 20
24162365 2013
19
A deep intronic mutation in the SLC12A3 gene leads to Gitelman syndrome. 54 61
19668106 2009
20
Identification of five novel variants in the thiazide-sensitive NaCl co-transporter gene in Chinese patients with Gitelman syndrome. 61 54
19207868 2009
21
Reduced urinary excretion of thiazide-sensitive Na-Cl cotransporter in Gitelman syndrome: preliminary data. 54 61
17954289 2007
22
Transcriptional and functional analyses of SLC12A3 mutations: new clues for the pathogenesis of Gitelman syndrome. 61 54
17329572 2007
23
Atypical Gitelman syndrome with L623P mutation of the thiazide-sensitive Na-Cl cotransporter gene exhibiting lack of hypocalciuria and increased proximal tubule salt reabsorption. 61 54
16854846 2006
24
A novel splicing mutation in SLC12A3 associated with Gitelman syndrome and idiopathic intracranial hypertension. 61 54
17059986 2006
25
Gitelman syndrome: genetic and expression analysis of the thiazide-sensitive sodium-chloride transporter in blood cells. 61 54
16221718 2006
26
Genetic analysis of Gitelman syndrome patients from the Czech Republic and Slovakia--three novel mutations found. 54 61
17159356 2006
27
A novel mutation of the thiazide-sensitive sodium chloride cotransporter gene in a Japanese family with Gitelman syndrome. 61 54
16429844 2006
28
Chondrocalcinosis secondary to hypomagnesemia in Gitelman's syndrome. 54 61
16142886 2005
29
Renal tubular transport and the genetic basis of hypertensive disease. 54 61
15980941 2005
30
Intrafamilial phenotype variability in patients with Gitelman syndrome having the same mutations in their thiazide-sensitive sodium/chloride cotransporter. 61 54
14750096 2004
31
A new mutation (intron 9 +1 G>T) in the SLC12A3 gene is linked to Gitelman syndrome in Gypsies. 54 61
14675033 2004
32
[Chondrocalcinosis and hypomagnesaemia in a patient with a new mutation in the gene of the thiazide-sensitive Na-Cl cotransporter]. 61 54
15002785 2003
33
[Gitelman syndrome. An overlooked disease with chronic hypomagnesemia and hypokalemia in adults]. 54 61
12677988 2003
34
Two novel mutations of thiazide-sensitive Na-Cl cotrans porter (TSC) gene in two sporadic Japanese patients with Gitelman syndrome. 54 61
12008755 2002
35
Inherited primary renal tubular hypokalemic alkalosis: a review of Gitelman and Bartter syndromes. 61 54
11780689 2001
36
Inherited disorders of renal magnesium handling. 61 54
11004227 2000
37
Thiazide-induced vasodilation in humans is mediated by potassium channel activation. 61 54
9856976 1998
38
Concomitant occurrence of Gitelman and Bartter syndromes in the same family? 54 61
9502562 1998
39
Linkage of Gitelman syndrome to the thiazide-sensitive sodium-chloride cotransporter gene with identification of mutations in Dutch families. 54 61
8865231 1996
40
[The Bartter-like syndrome in 2 twins]. 54 61
8255271 1993
41
A novel homozygous mutation (p.N958K) of SLC12A3 in Gitelman syndrome is associated with endoplasmic reticulum stress. 61
32642858 2021
42
Phenotypic differences of mutation-negative cases in Gitelman syndrome clinically diagnosed in adulthood. 61
33348466 2021
43
Type-5 Bartter syndrome presenting with metabolic seizure in adulthood. 61
33597159 2021
44
Heterozygosity for a Pathogenic Variant in SLC12A3 That Causes Autosomal Recessive Gitelman Syndrome Is Associated with Lower Serum Potassium. 61
33542107 2021
45
Gitelman Syndrome: A Rare Case of Hypokalaemia and a Novel Mutation. 61
33585337 2021
46
Novel SLC12A3 mutation in Gitelman syndrome. 61
33462018 2021
47
Congenital chloride diarrhea in patient with SLC26A2 mutation - analysis of the clinical phenotype and differential diagnosis. 61
33599438 2021
48
Differential diagnosis of perinatal Bartter, Bartter and Gitelman syndromes. 61
33564404 2021
49
Kidney stones and moderate proteinuria as the rare manifestations of Gitelman syndrome. 61
33413160 2021
50
Outcome of primary tubular tubulopathies diagnosed in pediatric age. 61
33358363 2020

Variations for Gitelman Syndrome

ClinVar genetic disease variations for Gitelman Syndrome:

6 (show top 50) (show all 278)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SLC12A3 NM_001126108.2(SLC12A3):c.625C>T (p.Arg209Trp) SNV Pathogenic 8586 rs28936388 16:56904031-56904031 16:56870119-56870119
2 SLC12A3 NM_001126108.2(SLC12A3):c.1964G>T (p.Arg655Leu) SNV Pathogenic 8589 rs121909380 16:56920314-56920314 16:56886402-56886402
3 SLC12A3 NM_001126108.2(SLC12A3):c.1046C>T (p.Pro349Leu) SNV Pathogenic 8592 rs121909383 16:56906649-56906649 16:56872737-56872737
4 SLC12A3 SLC12A3, 3-BP DEL Deletion Pathogenic 8593
5 SLC12A3 NM_001126108.2(SLC12A3):c.1889G>T (p.Gly630Val) SNV Pathogenic 8594 rs121909384 16:56919240-56919240 16:56885328-56885328
6 SLC12A3 SLC12A3, 2-BP DEL, 2881AG Deletion Pathogenic 8597
7 SLC12A3 NM_001126108.2(SLC12A3):c.1338del (p.Thr446_Met447insTer) Deletion Pathogenic 279587 rs886041108 16:56913455-56913455 16:56879543-56879543
8 SLC12A3 NM_001126108.2(SLC12A3):c.2191G>A (p.Gly731Arg) SNV Pathogenic 562347 rs752101663 16:56921849-56921849 16:56887937-56887937
9 SLC12A3 NM_001126108.2(SLC12A3):c.2576del (p.Cys859fs) Deletion Pathogenic 522467 rs1555501632 16:56928497-56928497 16:56894585-56894585
10 SLC12A3 NM_001126108.2(SLC12A3):c.1926-1G>T SNV Pathogenic 8587 rs755560627 16:56920275-56920275 16:56886363-56886363
11 SLC12A3 NM_001126108.2(SLC12A3):c.2720+1G>T SNV Pathogenic 8590 rs1347239469 16:56933529-56933529 16:56899617-56899617
12 SLC12A3 NM_001126108.2(SLC12A3):c.1261T>C (p.Cys421Arg) SNV Pathogenic 8585 rs28936387 16:56913065-56913065 16:56879153-56879153
13 SLC12A3 NM_001126108.2(SLC12A3):c.1868T>C (p.Leu623Pro) SNV Pathogenic 8595 rs121909385 16:56919219-56919219 16:56885307-56885307
14 SLC12A3 NM_001126108.2(SLC12A3):c.488C>T (p.Thr163Met) SNV Pathogenic 8596 rs267607050 16:56902267-56902267 16:56868355-56868355
15 SLC12A3 NM_001126108.2(SLC12A3):c.1924C>G (p.Arg642Gly) SNV Pathogenic 397523 rs200697179 16:56919275-56919275 16:56885363-56885363
16 SLC12A3 NM_001126108.2(SLC12A3):c.35dup (p.Asp12fs) Duplication Pathogenic 975084 16:56899181-56899182 16:56865269-56865270
17 SLC12A3 NM_001126108.2(SLC12A3):c.473G>A (p.Arg158Gln) SNV Pathogenic 647629 rs1274973729 16:56902252-56902252 16:56868340-56868340
18 SLC12A3 NM_001126108.2(SLC12A3):c.1919A>G (p.Asn640Ser) SNV Pathogenic 267286 rs886039754 16:56919270-56919270 16:56885358-56885358
19 SLC12A3 NM_001126108.2(SLC12A3):c.237_238dup (p.Arg80fs) Duplication Pathogenic 653276 rs780299444 16:56899381-56899382 16:56865469-56865470
20 SLC12A3 NM_001126108.2(SLC12A3):c.1670-191C>T SNV Pathogenic 665361 rs374182921 16:56917770-56917770 16:56883858-56883858
21 SLC12A3 NM_001126108.2(SLC12A3):c.2856+1G>T SNV Pathogenic 372504 rs199974259 16:56936421-56936421 16:56902509-56902509
22 SLC12A3 NM_001126108.2(SLC12A3):c.2954G>A (p.Cys985Tyr) SNV Pathogenic 448395 rs199849117 16:56947205-56947205 16:56913293-56913293
23 SLC12A3 NM_001126108.2(SLC12A3):c.1456G>A (p.Asp486Asn) SNV Pathogenic 642516 rs753523115 16:56914054-56914054 16:56880142-56880142
24 SLC12A3 NM_001126108.2(SLC12A3):c.1489A>T (p.Lys497Ter) SNV Pathogenic 852297 16:56914087-56914087 16:56880175-56880175
25 SLC12A3 NM_001126108.2(SLC12A3):c.2089_2095del (p.Thr697fs) Deletion Pathogenic 448392 rs771701344 16:56920916-56920922 16:56887004-56887010
26 SLC12A3 NM_001126108.2(SLC12A3):c.1315G>A (p.Gly439Ser) SNV Pathogenic 586601 rs759377924 16:56913119-56913119 16:56879207-56879207
27 SLC12A3 NM_001126108.2(SLC12A3):c.1367del (p.Leu456fs) Deletion Pathogenic 974506 16:56913485-56913485 16:56879573-56879573
28 SLC12A3 NM_001126108.2(SLC12A3):c.1925G>A (p.Arg642His) SNV Pathogenic 319909 rs147901432 16:56919276-56919276 16:56885364-56885364
29 SLC12A3 NM_001126108.2(SLC12A3):c.1180+1G>T SNV Pathogenic 437426 rs749098014 16:56912074-56912074 16:56878162-56878162
30 SLC12A3 NM_001126108.2(SLC12A3):c.2554C>T (p.Arg852Cys) SNV Pathogenic 437926 rs373899077 16:56928475-56928475 16:56894563-56894563
31 SLC12A3 NM_001126108.2(SLC12A3):c.283del (p.Gln95fs) Deletion Pathogenic 448955 rs1555499234 16:56900982-56900982 16:56867070-56867070
32 SLC12A3 NM_001126108.2(SLC12A3):c.506-1G>A SNV Pathogenic 448398 rs201555148 16:56903640-56903640 16:56869728-56869728
33 SLC12A3 NM_001126108.2(SLC12A3):c.1195C>T (p.Arg399Cys) SNV Pathogenic 448391 rs775931992 16:56912999-56912999 16:56879087-56879087
34 SLC12A3 NM_001126108.2(SLC12A3):c.179C>T (p.Thr60Met) SNV Pathogenic 101514 rs371443644 16:56899326-56899326 16:56865414-56865414
35 SLC12A3 NM_001126108.2(SLC12A3):c.1276A>T (p.Asn426Tyr) SNV Pathogenic 403666 rs200817545 16:56913080-56913080 16:56879168-56879168
36 SLC12A3 NM_001126108.2(SLC12A3):c.1928C>T (p.Pro643Leu) SNV Pathogenic 417863 rs140012781 16:56920278-56920278 16:56886366-56886366
37 SLC12A3 NM_001126108.2(SLC12A3):c.1664C>T (p.Ser555Leu) SNV Pathogenic 642947 rs148038173 16:56916404-56916404 16:56882492-56882492
38 SLC12A3 NM_001126108.2(SLC12A3):c.1763C>T (p.Ala588Val) SNV Pathogenic/Likely pathogenic 8591 rs121909382 16:56918054-56918054 16:56884142-56884142
39 SLC12A3 NM_001126108.2(SLC12A3):c.1919A>G (p.Asn640Ser) SNV Likely pathogenic 267286 rs886039754 16:56919270-56919270 16:56885358-56885358
40 SLC12A3 NM_001126108.2(SLC12A3):c.2863C>T (p.Arg955Trp) SNV Likely pathogenic 319919 rs559626481 16:56938313-56938313 16:56904401-56904401
41 SLC12A3 NM_001126108.2(SLC12A3):c.247C>T (p.Arg83Trp) SNV Likely pathogenic 319889 rs201255508 16:56899394-56899394 16:56865482-56865482
42 SLC12A3 NM_001126108.2(SLC12A3):c.2495A>G (p.Asp832Gly) SNV Likely pathogenic 487479 rs1555501437 16:56926940-56926940 16:56893028-56893028
43 SLC12A3 NM_001126108.2(SLC12A3):c.55C>T (p.Arg19Cys) SNV Likely pathogenic 813955 rs374055486 16:56899202-56899202 16:56865290-56865290
44 SLC12A3 NM_001126108.2(SLC12A3):c.1964G>A (p.Arg655His) SNV Likely pathogenic 8588 rs121909380 16:56920314-56920314 16:56886402-56886402
45 SLC12A3 NM_001126108.2(SLC12A3):c.1963C>T (p.Arg655Cys) SNV Likely pathogenic 840885 16:56920313-56920313 16:56886401-56886401
46 SLC12A3 NM_001126108.2(SLC12A3):c.2549T>C (p.Leu850Pro) SNV Likely pathogenic 8584 rs121909379 16:56928470-56928470 16:56894558-56894558
47 SLC12A3 NM_001126108.2(SLC12A3):c.2660G>A (p.Arg887Gln) SNV Likely pathogenic 805469 rs369360334 16:56933468-56933468 16:56899556-56899556
48 SLC12A3 NM_001126108.2(SLC12A3):c.2721-1G>A SNV Likely pathogenic 651512 rs761242621 16:56936284-56936284 16:56902372-56902372
49 SLC12A3 NM_001126108.2(SLC12A3):c.938C>T (p.Ala313Val) SNV Likely pathogenic 448400 rs140551719 16:56906348-56906348 16:56872436-56872436
50 SLC12A3 NM_001126108.2(SLC12A3):c.1180G>A (p.Gly394Ser) SNV Likely pathogenic 992416 16:56912073-56912073 16:56878161-56878161

UniProtKB/Swiss-Prot genetic disease variations for Gitelman Syndrome:

73 (show top 50) (show all 117)
# Symbol AA change Variation ID SNP ID
1 SLC12A3 p.Arg209Trp VAR_007113 rs28936388
2 SLC12A3 p.Pro349Leu VAR_007114 rs121909383
3 SLC12A3 p.Cys421Arg VAR_007115 rs28936387
4 SLC12A3 p.Asp486Asn VAR_007116 rs753523115
5 SLC12A3 p.Gly496Cys VAR_007117 rs777612082
6 SLC12A3 p.Ala588Val VAR_007119 rs121909382
7 SLC12A3 p.Gly630Val VAR_007120 rs121909384
8 SLC12A3 p.Arg655His VAR_007121 rs121909380
9 SLC12A3 p.Arg655Leu VAR_007122 rs121909380
10 SLC12A3 p.Gly741Arg VAR_007124 rs138977195
11 SLC12A3 p.Leu850Pro VAR_007125 rs121909379
12 SLC12A3 p.Arg955Gln VAR_007126 rs202114767
13 SLC12A3 p.Thr60Met VAR_039475 rs371443644
14 SLC12A3 p.Asp62Asn VAR_039476
15 SLC12A3 p.Glu68Lys VAR_039477 rs763210286
16 SLC12A3 p.His69Asn VAR_039478 rs780502516
17 SLC12A3 p.His90Tyr VAR_039479
18 SLC12A3 p.Arg145His VAR_039480 rs374324018
19 SLC12A3 p.Val153Met VAR_039481 rs779074538
20 SLC12A3 p.Ile154Phe VAR_039482 rs748547209
21 SLC12A3 p.Arg158Gln VAR_039483 rs127497372
22 SLC12A3 p.Thr163Met VAR_039484 rs267607050
23 SLC12A3 p.Trp172Arg VAR_039485 rs757792232
24 SLC12A3 p.Ser178Leu VAR_039486 rs772589653
25 SLC12A3 p.Thr180Lys VAR_039487 rs146158333
26 SLC12A3 p.Gly186Asp VAR_039488 rs759426055
27 SLC12A3 p.Arg209Gln VAR_039489 rs758035631
28 SLC12A3 p.Leu215Pro VAR_039490 rs780594361
29 SLC12A3 p.Ala226Thr VAR_039491 rs774753202
30 SLC12A3 p.Gly230Asp VAR_039492 rs375990084
31 SLC12A3 p.Arg261His VAR_039493 rs914588619
32 SLC12A3 p.Ser283Tyr VAR_039495 rs138003187
33 SLC12A3 p.Lys284Arg VAR_039496
34 SLC12A3 p.Thr304Pro VAR_039497 rs753840283
35 SLC12A3 p.Ala313Val VAR_039498 rs140551719
36 SLC12A3 p.Gly316Val VAR_039499 rs748920885
37 SLC12A3 p.Arg321Trp VAR_039500 rs150046661
38 SLC12A3 p.Arg334Trp VAR_039501 rs770702194
39 SLC12A3 p.Gly342Ala VAR_039502
40 SLC12A3 p.Gly374Val VAR_039503 rs773669504
41 SLC12A3 p.Arg399Cys VAR_039504 rs775931992
42 SLC12A3 p.Gly439Ser VAR_039505 rs759377924
43 SLC12A3 p.Gly463Glu VAR_039506 rs137551552
44 SLC12A3 p.Ala464Thr VAR_039507 rs201945662
45 SLC12A3 p.Lys478Glu VAR_039508 rs135570504
46 SLC12A3 p.Leu542Pro VAR_039509 rs574357286
47 SLC12A3 p.Ser555Leu VAR_039510 rs148038173
48 SLC12A3 p.Pro560His VAR_039511 rs140244480
49 SLC12A3 p.Ala569Glu VAR_039512 rs79351185
50 SLC12A3 p.Ala569Val VAR_039513 rs79351185

Copy number variations for Gitelman Syndrome from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 102593 16 55456619 55507263 ,deletion SLC12A3 Gitelman Syndrome
2 102594 16 55456619 55507263 Genomic rearrangement SLC12A3 Gitelman Syndrome

Expression for Gitelman Syndrome

Search GEO for disease gene expression data for Gitelman Syndrome.

Pathways for Gitelman Syndrome

Pathways related to Gitelman Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.94 WNK4 WNK3 WNK1 TRPM6 SLC12A3 SLC12A1
2
Show member pathways
12 WNK4 WNK3 WNK1 TRPM6 CLCNKB CLCNKA
3
Show member pathways
11.49 KCNJ16 KCNJ10 KCNJ1
4 10.78 WNK4 WNK3 WNK1 STK39 SLC12A3 SLC12A1

GO Terms for Gitelman Syndrome

Cellular components related to Gitelman Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 10.1 TRPM6 SLC12A3 SLC12A1 REN KCNJ16 KCNJ10
2 membrane GO:0016020 10.06 WNK4 WNK1 TRPM6 STK39 STK24 SLC12A3
3 integral component of plasma membrane GO:0005887 9.8 TRPM6 SLC12A3 KCNJ10 CLCNKB CLCNKA CASR
4 bicellular tight junction GO:0005923 9.54 WNK4 WNK3 CLDN16
5 apical plasma membrane GO:0016324 9.35 TRPM6 STK39 SLC12A3 SLC12A1 CASR
6 basolateral plasma membrane GO:0016323 9.02 STK39 KCNJ16 KCNJ10 CASR BSND

Biological processes related to Gitelman Syndrome according to GeneCards Suite gene sharing:

(show all 33)
# Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 10.1 WNK4 WNK3 WNK1 TRPM6 STK39 STK24
2 protein phosphorylation GO:0006468 10.08 WNK4 WNK3 WNK1 TRPM6 STK39 STK24
3 transmembrane transport GO:0055085 10.06 TRPM6 SLC12A3 SLC12A1 CLCNKB CLCNKA
4 protein autophosphorylation GO:0046777 9.92 WNK3 WNK1 STK39 STK24
5 regulation of ion transmembrane transport GO:0034765 9.89 KCNJ16 KCNJ10 KCNJ1 CLCNKB CLCNKA
6 potassium ion transport GO:0006813 9.88 SLC12A1 KCNJ16 KCNJ10 KCNJ1
7 chloride transport GO:0006821 9.83 WNK4 CLCNKB CLCNKA BSND
8 peptidyl-threonine phosphorylation GO:0018107 9.81 WNK3 WNK1 STK39
9 regulation of blood pressure GO:0008217 9.8 STK39 REN AGT
10 ion transmembrane transport GO:0034220 9.76 TRPM6 SLC12A1 KCNJ16 KCNJ10 KCNJ1 CLCNKB
11 chloride transmembrane transport GO:1902476 9.73 SLC12A3 SLC12A1 CLCNKB CLCNKA CASR BSND
12 potassium ion import across plasma membrane GO:1990573 9.72 SLC12A3 SLC12A1 KCNJ16 KCNJ10 KCNJ1
13 cell volume homeostasis GO:0006884 9.71 WNK3 SLC12A3 SLC12A1
14 excretion GO:0007588 9.71 KCNJ1 CLDN16 CLCNKB CLCNKA
15 potassium ion homeostasis GO:0055075 9.69 SLC12A3 SLC12A1 KCNJ10
16 regulation of long-term neuronal synaptic plasticity GO:0048169 9.65 KCNJ10 AGT
17 cellular response to chemokine GO:1990869 9.65 WNK1 STK39
18 sodium ion homeostasis GO:0055078 9.65 SLC12A3 SLC12A1
19 positive regulation of sodium ion transmembrane transporter activity GO:2000651 9.65 WNK4 WNK3 WNK1
20 positive regulation of T cell chemotaxis GO:0010820 9.64 WNK1 STK39
21 chloride ion homeostasis GO:0055064 9.64 SLC12A3 SLC12A1
22 positive regulation of potassium ion import GO:1903288 9.63 WNK4 WNK3 WNK1
23 renal sodium ion absorption GO:0070294 9.61 WNK4 KLHL3
24 positive regulation of ion transmembrane transporter activity GO:0032414 9.61 WNK3 STK39
25 negative regulation of sodium ion transport GO:0010766 9.61 WNK4 WNK3 WNK1
26 renin-angiotensin regulation of aldosterone production GO:0002018 9.59 REN AGT
27 regulation of cation transmembrane transport GO:1904062 9.58 WNK3 WNK1
28 distal tubule morphogenesis GO:0072156 9.57 WNK4 KLHL3
29 regulation of cellular process GO:0050794 9.56 WNK4 WNK1
30 regulation of blood volume by renin-angiotensin GO:0002016 9.55 REN AGT
31 negative regulation of pancreatic juice secretion GO:0090188 9.54 WNK4 WNK1 STK39
32 ion transport GO:0006811 9.36 WNK4 WNK1 TRPM6 SLC12A3 SLC12A1 KCNJ16
33 ion homeostasis GO:0050801 9.35 WNK4 WNK3 WNK1 STK39 KLHL3

Molecular functions related to Gitelman Syndrome according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 10.13 WNK4 WNK3 WNK1 TRPM6 STK39 STK24
2 ATP binding GO:0005524 10.01 WNK4 WNK3 WNK1 TRPM6 STK39 STK24
3 protein kinase activity GO:0004672 9.95 WNK4 WNK3 WNK1 STK39 STK24
4 kinase activity GO:0016301 9.91 WNK4 WNK3 WNK1 TRPM6 STK39 STK24
5 protein serine/threonine kinase activity GO:0004674 9.8 WNK4 WNK3 WNK1 TRPM6 STK39 STK24
6 chloride channel activity GO:0005254 9.67 CLCNKB CLCNKA BSND
7 voltage-gated ion channel activity GO:0005244 9.55 KCNJ16 KCNJ10 KCNJ1 CLCNKB CLCNKA
8 voltage-gated chloride channel activity GO:0005247 9.54 CLCNKB CLCNKA
9 potassium:chloride symporter activity GO:0015379 9.51 SLC12A3 SLC12A1
10 cation:chloride symporter activity GO:0015377 9.48 SLC12A3 SLC12A1
11 ATP-activated inward rectifier potassium channel activity GO:0015272 9.46 KCNJ10 KCNJ1
12 inward rectifier potassium channel activity GO:0005242 9.43 KCNJ16 KCNJ10 KCNJ1
13 sodium:potassium:chloride symporter activity GO:0008511 9.37 SLC12A3 SLC12A1
14 chloride channel inhibitor activity GO:0019869 9.13 WNK4 WNK3 WNK1
15 potassium channel inhibitor activity GO:0019870 8.8 WNK4 WNK3 WNK1

Sources for Gitelman Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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