MCID: HYP210
MIFTS: 36

Hypomagnesemia 2, Renal

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

Aliases & Classifications for Hypomagnesemia 2, Renal

MalaCards integrated aliases for Hypomagnesemia 2, Renal:

Name: Hypomagnesemia 2, Renal 57 73
Homg2 57 12 53 59 75
Autosomal Dominant Primary Hypomagnesemia with Hypocalciuria 12 53 59
Magnesium Wasting, Renal 57 53 55
Renal Magnesium Wasting 75 29 6
Renal Hypomagnesemia 2 12 53 75
Isolated Autosomal Dominant Hypomagnesemia 53 59
Isolated Renal Magnesium Wasting 53 59
Magnesium Loss, Isolated Renal 57 53
Renal Hypomagnesemia Type 2 53 59
Hypomagnesemia with Hypocalciuria 75
Renal Hypomagnesemia, Dominant 6
Dominant Renal Hypomagnesemia 75
Isolated Renal Magnesium Loss 75
Hypomagnesemia, Type 2, Renal 40
Hypomagnesemia-2, Renal 13
Hypomagnesemia 2 75

Characteristics:

Orphanet epidemiological data:

59
autosomal dominant primary hypomagnesemia with hypocalciuria
Inheritance: Autosomal dominant; Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
hypomagnesemia 2, renal:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 154020
Disease Ontology 12 DOID:0060885
ICD10 33 E83.4
Orphanet 59 ORPHA34528
UMLS via Orphanet 74 C1835171
ICD10 via Orphanet 34 E83.4
MedGen 42 C1835171
MeSH 44 D015499
UMLS 73 C1835171

Summaries for Hypomagnesemia 2, Renal

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 34528Disease definitionAutosomal dominant primary hypomagnesemia with hypocalciuria (ADPHH) is a mild form of familial primary hypomagnesemia (FPH, see this term), characterized by extreme weakness, tetany and convulsions. Secondary disturbances in calcium excretion are observed.EpidemiologyTo date, only one large pedigree with 18 affected individuals has been reported in the literature.Clinical descriptionADPHH can be detected in childhood or in adult life. Most affected individuals are asymptomatic but patients may suffer from generalized convulsions. In adulthood, chondrocalcinosis may be observed.EtiologyADPHH is caused by mutations in the FXYD2 gene (11q23; mutation p.Gly41Arg) which encodes the gamma subunit of the Na+/K+-ATPase, localized on the basolateral membranes of nephron epithelial cells and expressed in the distal convoluted tubule. A similar phenotype is observed in about 45-65% of patients with mutations in the HNF1Bgene (hepatocyte nuclear factor 1B; 17q12), which encodes a transcription factor expressed in renal epithelia. Indeed, this transcription factor stimulates transcriptional expression of the FXYD2 gene. Hypokalemia is observed in 46% of patients with HNF1B gene mutations.Diagnostic methodsDiagnosis relies on a hypomagnesemia, hypermagnesuria and hypocalciuria phenotype. In patients with FXYD2 mutations, no hypokalemia or metabolic alkalosis is observed. In contrast, in patients with HNF1B mutations, hypokalemia can be detected. Diagnosis is confirmed by the genetic screening of the genes FXYD2 and HNF1B.Differential diagnosisDifferential diagnosis includes all causes of renal hypomagnesemia, particularly diseases associated with hypocalciuria such as Gitelman syndrome, EAST syndrome and familial primary hypomagnesemia with normocalciuria and normocalcemia (see these terms).Antenatal diagnosisPrenatal diagnosis relies on detection of bilateral hyperechogenic kidneys of normal or moderately enlarged size by ultrasound in patients with HNF1B mutations.Genetic counselingTransmission is autosomal dominant. Genetic counseling may be proposed and the recurrence risk is 50%.Management and treatmentManagement is mainly symptomatic and includes oral magnesium supplements.Visit the Orphanet disease page for more resources.

MalaCards based summary : Hypomagnesemia 2, Renal, also known as homg2, is related to isolated autosomal dominant hypomagnesemia, glaudemans type and hypomagnesemia 5, renal, with ocular involvement, and has symptoms including seizures and weakness. An important gene associated with Hypomagnesemia 2, Renal is FXYD2 (FXYD Domain Containing Ion Transport Regulator 2). The drugs Magnesium oxide and Zinc have been mentioned in the context of this disorder. Affiliated tissues include kidney, and related phenotypes are seizures and renal insufficiency

Disease Ontology : 12 A hypomagnesemia characterized by autosomal dominant inheritance of hypomagnesemia due to renal magnesium loss that has material basis in heterozygous mutation in the FXYD2 gene on chromosome 11q23.

UniProtKB/Swiss-Prot : 75 Hypomagnesemia 2: A disorder due to primary renal wasting of magnesium. Plasma levels of other electrolytes are normal. The only abnormality found, in addition to low magnesium levels, is lowered renal excretion of calcium resulting in hypocalciuria.

Description from OMIM: 154020

Related Diseases for Hypomagnesemia 2, Renal

Diseases in the Hypomagnesemia 2, Renal family:

Hypomagnesemia 3, Renal Hypomagnesemia 4, Renal
Hypomagnesemia 6, Renal

Diseases related to Hypomagnesemia 2, Renal via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 isolated autosomal dominant hypomagnesemia, glaudemans type 12.2
2 hypomagnesemia 5, renal, with ocular involvement 11.2
3 gitelman syndrome 11.2
4 hypomagnesemia 3, renal 11.1
5 primary hypomagnesemia 9.6 CLDN16 FXYD2
6 ovarian clear cell carcinoma 9.0 FXYD2 HNF1B

Graphical network of the top 20 diseases related to Hypomagnesemia 2, Renal:



Diseases related to Hypomagnesemia 2, Renal

Symptoms & Phenotypes for Hypomagnesemia 2, Renal

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
dysesthesias of face and hands

Muscle Soft Tissue:
chondrocalcinosis
muscle cramping, especially of legs
generalized weakness

Laboratory Abnormalities:
hypokalemia
hypomagnesemia
hypocalciuria
normal parathyroid hormone
hypermagnesuria

Genitourinary Kidneys:
renal magnesium wasting
decreased renal calcium excretion
renal failure (rare)


Clinical features from OMIM:

154020

Human phenotypes related to Hypomagnesemia 2, Renal:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 renal insufficiency 32 occasional (7.5%) HP:0000083
3 hypokalemia 32 HP:0002900
4 generalized muscle weakness 32 HP:0003324
5 chondrocalcinosis 32 HP:0000934
6 hypomagnesemia 32 HP:0002917
7 hypocalciuria 32 HP:0003127
8 renal magnesium wasting 32 HP:0005567

UMLS symptoms related to Hypomagnesemia 2, Renal:


seizures, weakness

GenomeRNAi Phenotypes related to Hypomagnesemia 2, Renal according to GeneCards Suite gene sharing:

26 (show all 35)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 9.8 FXYD2
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-111 9.8 FXYD2
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-119 9.8 HNF1B
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-150 9.8 HNF1B
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-167 9.8 HNF1B
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-173 9.8 FXYD2
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-184 9.8 HNF1B
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-22 9.8 FXYD2
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-27 9.8 HNF1B
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 9.8 HNF1B
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-75 9.8 FXYD2
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-77 9.8 FXYD2 HNF1B
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 9.8 FXYD2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-102 9.68 FXYD2
15 Increased shRNA abundance (Z-score > 2) GR00366-A-105 9.68 FXYD2
16 Increased shRNA abundance (Z-score > 2) GR00366-A-116 9.68 FXYD2
17 Increased shRNA abundance (Z-score > 2) GR00366-A-152 9.68 FXYD2
18 Increased shRNA abundance (Z-score > 2) GR00366-A-157 9.68 HNF1B
19 Increased shRNA abundance (Z-score > 2) GR00366-A-158 9.68 FXYD2
20 Increased shRNA abundance (Z-score > 2) GR00366-A-164 9.68 FXYD2
21 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.68 HNF1B
22 Increased shRNA abundance (Z-score > 2) GR00366-A-183 9.68 FXYD2
23 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.68 HNF1B
24 Increased shRNA abundance (Z-score > 2) GR00366-A-19 9.68 FXYD2
25 Increased shRNA abundance (Z-score > 2) GR00366-A-195 9.68 FXYD2
26 Increased shRNA abundance (Z-score > 2) GR00366-A-197 9.68 FXYD2
27 Increased shRNA abundance (Z-score > 2) GR00366-A-210 9.68 FXYD2
28 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.68 HNF1B
29 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.68 HNF1B
30 Increased shRNA abundance (Z-score > 2) GR00366-A-49 9.68 HNF1B
31 Increased shRNA abundance (Z-score > 2) GR00366-A-5 9.68 HNF1B FXYD2
32 Increased shRNA abundance (Z-score > 2) GR00366-A-52 9.68 FXYD2
33 Increased shRNA abundance (Z-score > 2) GR00366-A-8 9.68 HNF1B
34 Increased shRNA abundance (Z-score > 2) GR00366-A-80 9.68 HNF1B
35 Increased shRNA abundance (Z-score > 2) GR00366-A-99 9.68 FXYD2

Drugs & Therapeutics for Hypomagnesemia 2, Renal

Drugs for Hypomagnesemia 2, Renal (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Magnesium oxide Approved Not Applicable 1309-48-4 14792
2
Zinc Approved, Investigational Not Applicable 7440-66-6 23994
3 Hypoglycemic Agents Not Applicable
4 insulin Not Applicable
5 Insulin, Globin Zinc Not Applicable
6 Magnesium Supplement Nutraceutical Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 The Impact of Magnesium Supplementation on Insulin Resistance and Secretion in Renal Transplant Recipients Completed NCT01291030 Not Applicable

Search NIH Clinical Center for Hypomagnesemia 2, Renal

Genetic Tests for Hypomagnesemia 2, Renal

Genetic tests related to Hypomagnesemia 2, Renal:

# Genetic test Affiliating Genes
1 Renal Magnesium Wasting 29 FXYD2

Anatomical Context for Hypomagnesemia 2, Renal

MalaCards organs/tissues related to Hypomagnesemia 2, Renal:

41
Kidney

Publications for Hypomagnesemia 2, Renal

Articles related to Hypomagnesemia 2, Renal:

# Title Authors Year
1
Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement. ( 17033971 )
2006

Variations for Hypomagnesemia 2, Renal

UniProtKB/Swiss-Prot genetic disease variations for Hypomagnesemia 2, Renal:

75
# Symbol AA change Variation ID SNP ID
1 FXYD2 p.Gly41Arg VAR_013280 rs28938168

ClinVar genetic disease variations for Hypomagnesemia 2, Renal:

6
(show top 50) (show all 110)
# Gene Variation Type Significance SNP ID Assembly Location
1 FXYD2 NM_021603.3(FXYD2): c.115G> A (p.Gly39Arg) single nucleotide variant Pathogenic rs28938168 GRCh37 Chromosome 11, 117693139: 117693139
2 FXYD2 NM_021603.3(FXYD2): c.115G> A (p.Gly39Arg) single nucleotide variant Pathogenic rs28938168 GRCh38 Chromosome 11, 117822424: 117822424
3 CNNM2 NM_017649.4(CNNM2): c.-110A> T single nucleotide variant Likely benign rs555951352 GRCh37 Chromosome 10, 104678128: 104678128
4 CNNM2 NM_017649.4(CNNM2): c.49C> G (p.Gln17Glu) single nucleotide variant Uncertain significance rs886046669 GRCh37 Chromosome 10, 104678286: 104678286
5 CNNM2 NM_017649.4(CNNM2): c.49C> G (p.Gln17Glu) single nucleotide variant Uncertain significance rs886046669 GRCh38 Chromosome 10, 102918529: 102918529
6 CNNM2 NM_017649.4(CNNM2): c.1764C> T (p.Tyr588=) single nucleotide variant Uncertain significance rs747058788 GRCh37 Chromosome 10, 104809606: 104809606
7 CNNM2 NM_017649.4(CNNM2): c.1764C> T (p.Tyr588=) single nucleotide variant Uncertain significance rs747058788 GRCh38 Chromosome 10, 103049849: 103049849
8 CNNM2 NM_017649.4(CNNM2): c.2310C> T (p.Ala770=) single nucleotide variant Benign rs943037 GRCh38 Chromosome 10, 103076162: 103076162
9 CNNM2 NM_017649.4(CNNM2): c.2310C> T (p.Ala770=) single nucleotide variant Benign rs943037 GRCh37 Chromosome 10, 104835919: 104835919
10 CNNM2 NM_017649.4(CNNM2): c.2544C> T (p.Asp848=) single nucleotide variant Benign rs35647154 GRCh37 Chromosome 10, 104836853: 104836853
11 CNNM2 NM_017649.4(CNNM2): c.2544C> T (p.Asp848=) single nucleotide variant Benign rs35647154 GRCh38 Chromosome 10, 103077096: 103077096
12 CNNM2 NM_017649.4(CNNM2): c.*455C> T single nucleotide variant Likely benign rs3740389 GRCh37 Chromosome 10, 104837392: 104837392
13 CNNM2 NM_017649.4(CNNM2): c.*455C> T single nucleotide variant Likely benign rs3740389 GRCh38 Chromosome 10, 103077635: 103077635
14 CNNM2 NM_017649.4(CNNM2): c.*528G> A single nucleotide variant Benign rs3740388 GRCh37 Chromosome 10, 104837465: 104837465
15 CNNM2 NM_017649.4(CNNM2): c.*528G> A single nucleotide variant Benign rs3740388 GRCh38 Chromosome 10, 103077708: 103077708
16 CNNM2 NM_017649.4(CNNM2): c.*619A> G single nucleotide variant Likely benign rs138807273 GRCh37 Chromosome 10, 104837556: 104837556
17 CNNM2 NM_017649.4(CNNM2): c.*619A> G single nucleotide variant Likely benign rs138807273 GRCh38 Chromosome 10, 103077799: 103077799
18 CNNM2 NM_017649.4(CNNM2): c.*686T> A single nucleotide variant Uncertain significance rs886046674 GRCh37 Chromosome 10, 104837623: 104837623
19 CNNM2 NM_017649.4(CNNM2): c.*686T> A single nucleotide variant Uncertain significance rs886046674 GRCh38 Chromosome 10, 103077866: 103077866
20 CNNM2 NM_017649.4(CNNM2): c.*811A> G single nucleotide variant Uncertain significance rs886046676 GRCh37 Chromosome 10, 104837748: 104837748
21 CNNM2 NM_017649.4(CNNM2): c.*811A> G single nucleotide variant Uncertain significance rs886046676 GRCh38 Chromosome 10, 103077991: 103077991
22 CNNM2 NM_017649.4(CNNM2): c.*834C> T single nucleotide variant Uncertain significance rs886046677 GRCh37 Chromosome 10, 104837771: 104837771
23 CNNM2 NM_017649.4(CNNM2): c.*834C> T single nucleotide variant Uncertain significance rs886046677 GRCh38 Chromosome 10, 103078014: 103078014
24 CNNM2 NM_017649.4(CNNM2): c.*873G> A single nucleotide variant Uncertain significance rs886046678 GRCh37 Chromosome 10, 104837810: 104837810
25 CNNM2 NM_017649.4(CNNM2): c.*873G> A single nucleotide variant Uncertain significance rs886046678 GRCh38 Chromosome 10, 103078053: 103078053
26 CNNM2 NM_017649.4(CNNM2): c.*1162G> A single nucleotide variant Likely benign rs148051463 GRCh37 Chromosome 10, 104838099: 104838099
27 CNNM2 NM_017649.4(CNNM2): c.*1162G> A single nucleotide variant Likely benign rs148051463 GRCh38 Chromosome 10, 103078342: 103078342
28 CNNM2 NM_017649.4(CNNM2): c.*1246G> C single nucleotide variant Uncertain significance rs553490290 GRCh37 Chromosome 10, 104838183: 104838183
29 CNNM2 NM_017649.4(CNNM2): c.*1246G> C single nucleotide variant Uncertain significance rs553490290 GRCh38 Chromosome 10, 103078426: 103078426
30 FXYD2 NM_001680.4(FXYD2): c.*215G> A single nucleotide variant Likely benign rs41304349 GRCh37 Chromosome 11, 117690879: 117690879
31 FXYD2 NM_001680.4(FXYD2): c.*215G> A single nucleotide variant Likely benign rs41304349 GRCh38 Chromosome 11, 117820164: 117820164
32 FXYD2 NM_001680.4(FXYD2): c.*124T> A single nucleotide variant Uncertain significance rs756608243 GRCh37 Chromosome 11, 117690970: 117690970
33 FXYD2 NM_001680.4(FXYD2): c.*124T> A single nucleotide variant Uncertain significance rs756608243 GRCh38 Chromosome 11, 117820255: 117820255
34 FXYD2 NM_001680.4(FXYD2): c.*105C> T single nucleotide variant Likely benign rs78017409 GRCh37 Chromosome 11, 117690989: 117690989
35 FXYD2 NM_001680.4(FXYD2): c.*105C> T single nucleotide variant Likely benign rs78017409 GRCh38 Chromosome 11, 117820274: 117820274
36 FXYD2 NM_001680.4(FXYD2): c.*78C> A single nucleotide variant Likely benign rs114952534 GRCh37 Chromosome 11, 117691016: 117691016
37 FXYD2 NM_001680.4(FXYD2): c.*78C> A single nucleotide variant Likely benign rs114952534 GRCh38 Chromosome 11, 117820301: 117820301
38 FXYD2 NM_001680.4(FXYD2): c.183C> T (p.Ile61=) single nucleotide variant Likely benign rs201669990 GRCh37 Chromosome 11, 117691405: 117691405
39 FXYD2 NM_001680.4(FXYD2): c.183C> T (p.Ile61=) single nucleotide variant Likely benign rs201669990 GRCh38 Chromosome 11, 117820690: 117820690
40 CNNM2 NM_017649.4(CNNM2): c.-110A> T single nucleotide variant Likely benign rs555951352 GRCh38 Chromosome 10, 102918371: 102918371
41 CNNM2 NM_017649.4(CNNM2): c.342G> T (p.Thr114=) single nucleotide variant Likely benign rs375416482 GRCh37 Chromosome 10, 104678579: 104678579
42 CNNM2 NM_017649.4(CNNM2): c.342G> T (p.Thr114=) single nucleotide variant Likely benign rs375416482 GRCh38 Chromosome 10, 102918822: 102918822
43 CNNM2 NM_017649.4(CNNM2): c.801C> T (p.Cys267=) single nucleotide variant Likely benign rs367789750 GRCh37 Chromosome 10, 104679038: 104679038
44 CNNM2 NM_017649.4(CNNM2): c.801C> T (p.Cys267=) single nucleotide variant Likely benign rs367789750 GRCh38 Chromosome 10, 102919281: 102919281
45 CNNM2 NM_017649.4(CNNM2): c.1515C> T (p.Pro505=) single nucleotide variant Uncertain significance rs144140948 GRCh37 Chromosome 10, 104679752: 104679752
46 CNNM2 NM_017649.4(CNNM2): c.1515C> T (p.Pro505=) single nucleotide variant Uncertain significance rs144140948 GRCh38 Chromosome 10, 102919995: 102919995
47 CNNM2 NM_017649.4(CNNM2): c.*3C> T single nucleotide variant Benign rs2296568 GRCh37 Chromosome 10, 104836940: 104836940
48 CNNM2 NM_017649.4(CNNM2): c.*3C> T single nucleotide variant Benign rs2296568 GRCh38 Chromosome 10, 103077183: 103077183
49 CNNM2 NM_017649.4(CNNM2): c.*53G> A single nucleotide variant Uncertain significance rs886046672 GRCh38 Chromosome 10, 103077233: 103077233
50 CNNM2 NM_017649.4(CNNM2): c.*53G> A single nucleotide variant Uncertain significance rs886046672 GRCh37 Chromosome 10, 104836990: 104836990

Expression for Hypomagnesemia 2, Renal

Search GEO for disease gene expression data for Hypomagnesemia 2, Renal.

Pathways for Hypomagnesemia 2, Renal

GO Terms for Hypomagnesemia 2, Renal

Biological processes related to Hypomagnesemia 2, Renal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transmembrane transport GO:0034220 9.16 FXYD2 FXYD6-FXYD2
2 ion transport GO:0006811 9.13 CLDN16 FXYD2 FXYD6-FXYD2
3 regulation of sodium ion transmembrane transporter activity GO:2000649 8.62 FXYD2 FXYD6-FXYD2

Molecular functions related to Hypomagnesemia 2, Renal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sodium channel regulator activity GO:0017080 8.62 FXYD2 FXYD6-FXYD2

Sources for Hypomagnesemia 2, Renal

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