NSIAD
MCID: NPH013
MIFTS: 39

Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD)

Categories: Endocrine diseases, Genetic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Nephrogenic Syndrome of Inappropriate Antidiuresis

MalaCards integrated aliases for Nephrogenic Syndrome of Inappropriate Antidiuresis:

Name: Nephrogenic Syndrome of Inappropriate Antidiuresis 57 12 58 72 36 29 13 6 44 39 70
Nsiad 57 12 58 72

Characteristics:

Orphanet epidemiological data:

58
nephrogenic syndrome of inappropriate antidiuresis
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
x-linked recessive

Miscellaneous:
onset within first 3 months of life
normal neonatal course
caused by constitutive activation of the avpr2 receptor


HPO:

31
nephrogenic syndrome of inappropriate antidiuresis:
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare renal diseases


External Ids:

Disease Ontology 12 DOID:0112121
OMIM® 57 300539
KEGG 36 H01294
MeSH 44 C564491
SNOMED-CT 67 723440000
ICD10 via Orphanet 33 E22.2
UMLS via Orphanet 71 C1845202
Orphanet 58 ORPHA93606
MedGen 41 C1845202
UMLS 70 C1845202

Summaries for Nephrogenic Syndrome of Inappropriate Antidiuresis

OMIM® : 57 The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. The syndrome manifests as an inability to excrete a free water load, with inappropriately concentrated urine and resultant hyponatremia, hypoosmolality, and natriuresis. SIADH occurs in a setting of normal blood volume, without evidence of renal disease or deficiency of thyroxine or cortisol. Although usually transient, SIADH may be chronic; it is often associated with drug use or a lesion in the central nervous system or lung. When the cardinal features of SIADH were defined by Bartter and Schwartz (1967), levels of AVP could not be measured. Subsequently, radioimmunoassays revealed that SIADH is usually associated with measurably elevated serum levels of AVP. Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is characterized by a clinical picture similar to SIADH, but is associated with undetectable levels of AVP (Feldman et al., 2005). (300539) (Updated 20-May-2021)

MalaCards based summary : Nephrogenic Syndrome of Inappropriate Antidiuresis, also known as nsiad, is related to diabetes insipidus and diabetes insipidus, nephrogenic, autosomal, and has symptoms including seizures An important gene associated with Nephrogenic Syndrome of Inappropriate Antidiuresis is AVPR2 (Arginine Vasopressin Receptor 2), and among its related pathways/superpathways are Neuroactive ligand-receptor interaction and Vasopressin-regulated water reabsorption. Affiliated tissues include pituitary, kidney and liver, and related phenotypes are irritability and hyponatremia

Disease Ontology : 12 A renal tubular transport disease characterized by inappropriate antidiuretic hormone secretion resulting in inability to excrete a free water load, inappropriately concentrated urine, and undetectable or low plasma arginine vasopressin levels that has material basis in hemizygous gain-of-function mutation in AVPR2 on chromosome Xq28.

KEGG : 36 Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a disorder of water balance caused by gain of function mutation of arginine vasopressin receptor type 2 (AVPR2) resulting in free water reabsorption and episodes of hyponatremia.

UniProtKB/Swiss-Prot : 72 Nephrogenic syndrome of inappropriate antidiuresis: Characterized by an inability to excrete a free water load, with inappropriately concentrated urine and resultant hyponatremia, hypoosmolarity, and natriuresis.

Related Diseases for Nephrogenic Syndrome of Inappropriate Antidiuresis

Graphical network of the top 20 diseases related to Nephrogenic Syndrome of Inappropriate Antidiuresis:



Diseases related to Nephrogenic Syndrome of Inappropriate Antidiuresis

Symptoms & Phenotypes for Nephrogenic Syndrome of Inappropriate Antidiuresis

Human phenotypes related to Nephrogenic Syndrome of Inappropriate Antidiuresis:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 irritability 31 HP:0000737
2 hyponatremia 31 HP:0002902
3 decreased circulating renin level 31 HP:0003351
4 hypernatriuria 31 HP:0012605
5 decreased serum creatinine 31 HP:0012101
6 elevated systolic blood pressure 31 HP:0004421
7 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures

Laboratory Abnormalities:
hyponatremia
decreased serum osmolality
inappropriately increased urine osmolality
increased urinary sodium
decreased serum bun
more
Neurologic Behavioral Psychiatric Manifestations:
irritability

Cardiovascular Vascular:
systolic hypertension, mild

Clinical features from OMIM®:

300539 (Updated 20-May-2021)

UMLS symptoms related to Nephrogenic Syndrome of Inappropriate Antidiuresis:


seizures

MGI Mouse Phenotypes related to Nephrogenic Syndrome of Inappropriate Antidiuresis:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 renal/urinary system MP:0005367 8.8 AQP2 AVP AVPR2

Drugs & Therapeutics for Nephrogenic Syndrome of Inappropriate Antidiuresis

Search Clinical Trials , NIH Clinical Center for Nephrogenic Syndrome of Inappropriate Antidiuresis

Cochrane evidence based reviews: nephrogenic syndrome of inappropriate antidiuresis

Genetic Tests for Nephrogenic Syndrome of Inappropriate Antidiuresis

Genetic tests related to Nephrogenic Syndrome of Inappropriate Antidiuresis:

# Genetic test Affiliating Genes
1 Nephrogenic Syndrome of Inappropriate Antidiuresis 29 AVPR2

Anatomical Context for Nephrogenic Syndrome of Inappropriate Antidiuresis

MalaCards organs/tissues related to Nephrogenic Syndrome of Inappropriate Antidiuresis:

40
Pituitary, Kidney, Liver

Publications for Nephrogenic Syndrome of Inappropriate Antidiuresis

Articles related to Nephrogenic Syndrome of Inappropriate Antidiuresis:

(show top 50) (show all 60)
# Title Authors PMID Year
1
Nephrogenic syndrome of inappropriate antidiuresis. 61 57
15872203 2005
2
The syndrome of inappropriate secretion of antidiuretic hormone. 57
5337379 1967
3
[Diagnosis and follow-up of 2 cases of pediatric nephrogenic syndrome of inappropriate antidiuresis resulting from activating mutation in AVPR2 and literature review]. 61
33548959 2021
4
Protective effect of tolvaptan against cyclophosphamide-induced nephrotoxicity in rat models. 61
32996719 2020
5
Vasopressin receptor 2 mutations in the nephrogenic syndrome of inappropriate antidiuresis show different mechanisms of constitutive activation for G protein coupled receptors. 61
32499611 2020
6
The Vasopressin Receptor 2 Mutant R137L Linked to the Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD) Signals through an Alternative Pathway that Increases AQP2 Membrane Targeting Independently of S256 Phosphorylation. 61
32486031 2020
7
V2 vasopressin receptor mutations. 61
32138955 2020
8
Gain-of-function mutations of the V2 vasopressin receptor in nephrogenic syndrome of inappropriate antidiuresis (NSIAD): a cell-based assay to assess constitutive water reabsorption. 61
31486901 2019
9
Focus on neonatal and infantile onset of nephrogenic syndrome of inappropriate antidiuresis: 12 years later. 61
29546600 2019
10
Nephrogenic syndrome of inappropriate antidiuresis. 61
31083810 2019
11
Germline-Derived Gain-of-Function Variants of GsĪ±-Coding GNAS Gene Identified in Nephrogenic Syndrome of Inappropriate Antidiuresis. 61
30962325 2019
12
[Nephrogenic syndrome of inappropriate antidiuresis]. 61
31312322 2019
13
Nephrogenic Diabetes Insipidus. 61
31588538 2019
14
Vasopressin-aquaporin-2 pathway: recent advances in understanding water balance disorders. 61
30800291 2019
15
Internalization of NKCC2 is impaired in thick ascending limb of Henle in moesin knockout mice. 61
29541861 2018
16
A case of nephrogenic syndrome of inappropriate antidiuresis caused by carbamazepine. 61
29282644 2018
17
Adult female with symptomatic AVPR2-related nephrogenic syndrome of inappropriate antidiuresis (NSIAD). 61
29472987 2018
18
[Nephrogenic syndrome of inappropriate antidiuresis: Early diagnosis avoids severe hyponatremia complications]. 61
28583780 2017
19
Nephrogenic syndrome of inappropriate antidiuresis secondary to an activating mutation in the arginine vasopressin receptor AVPR2. 61
26715131 2016
20
Mutations of Vasopressin Receptor 2 Including Novel L312S Have Differential Effects on Trafficking. 61
27355191 2016
21
A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2. 61
27117808 2016
22
Ten common pitfalls in the evaluation of patients with hyponatremia. 61
26706473 2016
23
Sodium nitrate alleviates functional muscle ischaemia in patients with Becker muscular dystrophy. 61
26437761 2015
24
Mutation in the V2 vasopressin receptor gene, AVPR2, causes nephrogenic syndrome of inappropriate diuresis. 61
26131744 2015
25
Cyclophosphamide-induced vasopressin-independent activation of aquaporin-2 in the rat kidney. 61
26109089 2015
26
Approach to the treatment of the infant with hyponatremia. 61
25542409 2015
27
Nephrogenic Syndrome of Inappropriate Antidiuresis in a Female Neonate: Review of the Clinical Presentation in Females. 61
25925274 2015
28
[Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis]. 61
25449762 2014
29
Evaluation of the analgesic and anti-inflammatory activity of fixed dose combination: non-steroidal anti-inflammatory drugs in experimental animals. 61
25511049 2014
30
Prehospital use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of trauma-induced coagulopathy. 61
24424149 2014
31
Characteristics, prevalence, risk factors, and underlying mechanism of hyponatremia in elderly patients treated with antidepressants: a cross-sectional study. 61
24094459 2013
32
Transient nephrogenic syndrome of inappropriate antidiuresis. 61
27293575 2013
33
Functional polymorphisms affecting the clinically important arginine-137 residue of AVPR2 do not influence serum sodium concentration at the population level. 61
23362144 2013
34
Characterization of three vasopressin receptor 2 variants: an apparent polymorphism (V266A) and two loss-of-function mutations (R181C and M311V). 61
23762448 2013
35
Identification and characterization of an activating F229V substitution in the V2 vasopressin receptor in an infant with NSIAD. 61
22956819 2012
36
A family with hyponatremia and the nephrogenic syndrome of inappropriate antidiuresis. 61
22154540 2012
37
Lack of responsiveness to 1-desamino-D arginin vasopressin (desmopressin) in male patients with nephrogenic syndrome of inappropriate antidiuresis: from bench to bedside. 61
21834801 2012
38
Persistent elevation of urine aquaporin-2 during water loading in a child with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by a R137L mutation in the V2 vasopressin receptor. 61
22325688 2012
39
Long-term treatment of hyponatremic patients with nephrogenic syndrome of inappropriate antidiuresis: personal experience and review of published case reports. 61
22722264 2012
40
Nephrogenic syndrome of inappropriate antidiuresis. 61
22518188 2012
41
Expression, purification and NMR characterization of the cyclic recombinant form of the third intracellular loop of the vasopressin type 2 receptor. 61
21575724 2011
42
Nephrogenic syndrome of inappropriate antidiuresis. 61
20543212 2010
43
Familial nephrogenic syndrome of inappropriate antidiuresis: dissociation between aquaporin-2 and vasopressin excretion. 61
20631022 2010
44
Functional characterization of vasopressin type 2 receptor substitutions (R137H/C/L) leading to nephrogenic diabetes insipidus and nephrogenic syndrome of inappropriate antidiuresis: implications for treatments. 61
20159941 2010
45
The constitutively active V2 receptor mutants conferring NSIAD are weakly sensitive to agonist and antagonist regulation. 61
20027297 2009
46
Thirst perception and arginine vasopressin production in a kindred with an activating mutation of the type 2 vasopressin receptor: the pathophysiology of nephrogenic syndrome of inappropriate antidiuresis. 61
19542240 2009
47
The syndrome of inappropriate secretion of antidiuretic hormone (SIADH). 61
19523572 2009
48
Agonist-independent interactions between beta-arrestins and mutant vasopressin type II receptors associated with nephrogenic syndrome of inappropriate antidiuresis. 61
19179480 2009
49
Nephrogenic syndrome of inappropriate antidiuresis: a novel cause of euvolemic hypotonic hyponatremia in newborns. Diagnosis and practical management. 61
19925363 2009
50
Long-term outcomes in a family with nephrogenic syndrome of inappropriate antidiuresis. 61
20148077 2009

Variations for Nephrogenic Syndrome of Inappropriate Antidiuresis

ClinVar genetic disease variations for Nephrogenic Syndrome of Inappropriate Antidiuresis:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 AVPR2 NM_000054.6(AVPR2):c.409C>T (p.Arg137Cys) SNV Pathogenic 10854 rs104894761 GRCh37: X:153171369-153171369
GRCh38: X:153905915-153905915
2 AVPR2 NM_000054.6(AVPR2):c.410G>T (p.Arg137Leu) SNV Pathogenic 10855 rs104894756 GRCh37: X:153171370-153171370
GRCh38: X:153905916-153905916
3 AVPR2 NM_000054.6(AVPR2):c.26-6T>G SNV Benign 254772 rs56689668 GRCh37: X:153170980-153170980
GRCh38: X:153905526-153905526
4 AVPR2 NM_000054.6(AVPR2):c.797T>C (p.Val266Ala) SNV not provided 441086 rs111643041 GRCh37: X:153171757-153171757
GRCh38: X:153906303-153906303

UniProtKB/Swiss-Prot genetic disease variations for Nephrogenic Syndrome of Inappropriate Antidiuresis:

72
# Symbol AA change Variation ID SNP ID
1 AVPR2 p.Arg137Cys VAR_025901 rs104894761
2 AVPR2 p.Arg137Leu VAR_025902 rs104894756

Expression for Nephrogenic Syndrome of Inappropriate Antidiuresis

Search GEO for disease gene expression data for Nephrogenic Syndrome of Inappropriate Antidiuresis.

Pathways for Nephrogenic Syndrome of Inappropriate Antidiuresis

Pathways related to Nephrogenic Syndrome of Inappropriate Antidiuresis according to KEGG:

36
# Name Kegg Source Accession
1 Neuroactive ligand-receptor interaction hsa04080
2 Vasopressin-regulated water reabsorption hsa04962

Pathways related to Nephrogenic Syndrome of Inappropriate Antidiuresis according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.56 AVPR2 AVP AQP2
2
Show member pathways
11.76 AVPR2 AVP
3
Show member pathways
11.69 AVPR2 AVP
4
Show member pathways
11.55 AVPR2 AVP AQP2
5 11.32 AVPR2 AVP
6 10.44 AVPR2 AVP AQP2

GO Terms for Nephrogenic Syndrome of Inappropriate Antidiuresis

Cellular components related to Nephrogenic Syndrome of Inappropriate Antidiuresis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 clathrin-coated vesicle membrane GO:0030665 8.62 AVPR2 AVP

Biological processes related to Nephrogenic Syndrome of Inappropriate Antidiuresis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane organization GO:0061024 9.32 AVPR2 AVP
2 positive regulation of vasoconstriction GO:0045907 9.26 AVPR2 AVP
3 water transport GO:0006833 9.16 AVP AQP2
4 positive regulation of systemic arterial blood pressure GO:0003084 8.96 AVPR2 AVP
5 renal water homeostasis GO:0003091 8.8 AVPR2 AVP AQP2

Sources for Nephrogenic Syndrome of Inappropriate Antidiuresis

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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