HOMG2
MCID: HYP210
MIFTS: 40

Hypomagnesemia 2, Renal (HOMG2)

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

Aliases & Classifications for Hypomagnesemia 2, Renal

MalaCards integrated aliases for Hypomagnesemia 2, Renal:

Name: Hypomagnesemia 2, Renal 57 70
Renal Hypomagnesemia 2 12 20 72 29 6 15
Homg2 57 12 20 58 72
Autosomal Dominant Primary Hypomagnesemia with Hypocalciuria 12 20 58
Magnesium Wasting, Renal 57 20 54
Isolated Autosomal Dominant Hypomagnesemia 20 58
Isolated Renal Magnesium Wasting 20 58
Magnesium Loss, Isolated Renal 57 20
Renal Hypomagnesemia Type 2 20 58
Hypomagnesemia with Hypocalciuria 72
Renal Hypomagnesemia, Dominant 6
Dominant Renal Hypomagnesemia 72
Isolated Renal Magnesium Loss 72
Hypomagnesemia, Type 2, Renal 39
Renal Magnesium Wasting 72
Hypomagnesemia-2, Renal 13
Hypomagnesemia 2 72

Characteristics:

Orphanet epidemiological data:

58
autosomal dominant primary hypomagnesemia with hypocalciuria
Inheritance: Autosomal dominant; Age of onset: All ages; Age of death: normal life expectancy;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant


HPO:

31
hypomagnesemia 2, renal:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare renal diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0060885
OMIM® 57 154020
OMIM Phenotypic Series 57 PS602014
MeSH 44 D015499
ICD10 32 E83.4
ICD10 via Orphanet 33 E83.4
UMLS via Orphanet 71 C1835171
Orphanet 58 ORPHA34528
MedGen 41 C1835171
UMLS 70 C1835171

Summaries for Hypomagnesemia 2, Renal

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 34528 Definition A mild form of familial primary hypomagnesemia (FPH), characterized by extreme weakness, tetany and convulsions. Secondary disturbances in calcium excretion are observed. Epidemiology To date, only one large pedigree with 18 affected individuals has been reported in the literature. Clinical description Autosomal dominant primary hypomagnesemia with hypocalciuria (ADPHH) 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. Etiology ADPHH 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 HNF1B gene (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 methods Diagnosis 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 diagnosis Differential 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 diagnosis Prenatal diagnosis relies on detection of bilateral hyperechogenic kidneys of normal or moderately enlarged size by ultrasound in patients with HNF1B mutations. Genetic counseling Transmission is autosomal dominant. Genetic counseling may be proposed and the recurrence risk is 50%. Management and treatment Management is mainly symptomatic and includes oral magnesium supplements.

MalaCards based summary : Hypomagnesemia 2, Renal, also known as renal hypomagnesemia 2, is related to gitelman syndrome and hypomagnesemia 3, renal, and has symptoms including seizures and weakness. An important gene associated with Hypomagnesemia 2, Renal is FXYD2 (FXYD Domain Containing Ion Transport Regulator 2), and among its related pathways/superpathways are Renin secretion and Endocrine and other factor-regulated calcium reabsorption. Related phenotypes are renal insufficiency and hypokalemia

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 : 72 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.

More information from OMIM: 154020 PS602014

Related Diseases for Hypomagnesemia 2, Renal

Diseases in the Hypomagnesemia 3, Renal family:

Hypomagnesemia 2, Renal Hypomagnesemia 4, Renal
Hypomagnesemia 6, Renal

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

(show all 44)
# Related Disease Score Top Affiliating Genes
1 gitelman syndrome 32.0 FXYD2 CLDN16
2 hypomagnesemia 3, renal 31.9 FXYD2 CLDN16
3 primary hypomagnesemia 30.1 FXYD2 CLDN16
4 hypomagnesemia, seizures, and mental retardation 2 11.3
5 isolated autosomal dominant hypomagnesemia, glaudemans type 11.3
6 genetic primary hypomagnesemia with hypocalciuria 11.3
7 nephrocalcinosis 10.2
8 hypokalemia 10.1
9 bartter syndrome, type 3 10.1 FXYD2 CLDN16
10 renal cysts and diabetes syndrome 10.0
11 glycogen storage disease ii 10.0
12 hypomagnesemia 5, renal, with or without ocular involvement 10.0
13 hyperphenylalaninemia, bh4-deficient, d 10.0
14 maturity-onset diabetes of the young 10.0
15 mulchandani-bhoj-conlin syndrome 10.0
16 proteinuria, chronic benign 10.0
17 hypophosphatemia 10.0
18 hyperphosphatemia 10.0
19 metabolic acidosis 10.0
20 bone disease 10.0
21 short bowel syndrome 10.0
22 rickets 10.0
23 interstitial nephritis 10.0
24 myopia 10.0
25 renal osteodystrophy 10.0
26 renal tubular acidosis 10.0
27 hypothyroidism 10.0
28 leptospirosis 10.0
29 glycogen storage disease 10.0
30 acute kidney failure 10.0
31 osteitis fibrosa 10.0
32 bone inflammation disease 10.0
33 kidney disease 10.0
34 chronic kidney disease 10.0
35 hyperphenylalaninemia 10.0
36 tetrahydrobiopterin deficiency 10.0
37 47,xyy 10.0
38 distal renal tubular acidosis 10.0
39 hnf1b-related autosomal dominant tubulointerstitial kidney disease 10.0
40 dent disease 1 9.9 GRHPR CLDN16
41 nephrolithiasis, calcium oxalate 9.8 GRHPR CLDN16
42 hypocalcemia, autosomal dominant 1 9.8 GNAS CLDN16
43 oligohydramnios 9.8 HNF1B AQP1
44 polyhydramnios 9.7 HNF1B GNAS AQP1

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



Diseases related to Hypomagnesemia 2, Renal

Symptoms & Phenotypes for Hypomagnesemia 2, Renal

Human phenotypes related to Hypomagnesemia 2, Renal:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 renal insufficiency 31 occasional (7.5%) HP:0000083
2 hypokalemia 31 HP:0002900
3 chondrocalcinosis 31 HP:0000934
4 generalized muscle weakness 31 HP:0003324
5 hypocalciuria 31 HP:0003127
6 hypomagnesemia 31 HP:0002917
7 renal magnesium wasting 31 HP:0005567
8 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
dysesthesias of face and hands

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

Laboratory Abnormalities:
hypokalemia
hypocalciuria
hypomagnesemia
normal parathyroid hormone
hypermagnesuria

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

Clinical features from OMIM®:

154020 (Updated 05-Apr-2021)

UMLS symptoms related to Hypomagnesemia 2, Renal:


seizures; weakness

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

26 (show top 50) (show all 57)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-102 10.5 FXYD2
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 10.5 FXYD2
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-105 10.5 FXYD2
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-111 10.5 FXYD2
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-120 10.5 IFT57
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-133 10.5 IFT57
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-150 10.5 HNF1B
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-152 10.5 FXYD2
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-157 10.5 HNF1B
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-158 10.5 FXYD2
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-167 10.5 HNF1B
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-173 10.5 FXYD2
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 10.5 HNF1B
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-179 10.5 IFT57
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-183 10.5 FXYD2
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-184 10.5 HNF1B
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-185 10.5 HNF1B
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-191 10.5 IFT57
19 Decreased shRNA abundance (Z-score < -2) GR00366-A-20 10.5 IFT57
20 Decreased shRNA abundance (Z-score < -2) GR00366-A-214 10.5 HNF1B
21 Decreased shRNA abundance (Z-score < -2) GR00366-A-22 10.5 FXYD2
22 Decreased shRNA abundance (Z-score < -2) GR00366-A-27 10.5 HNF1B
23 Decreased shRNA abundance (Z-score < -2) GR00366-A-31 10.5 IFT57
24 Decreased shRNA abundance (Z-score < -2) GR00366-A-37 10.5 IFT57
25 Decreased shRNA abundance (Z-score < -2) GR00366-A-38 10.5 IFT57
26 Decreased shRNA abundance (Z-score < -2) GR00366-A-43 10.5 HNF1B
27 Decreased shRNA abundance (Z-score < -2) GR00366-A-49 10.5 HNF1B
28 Decreased shRNA abundance (Z-score < -2) GR00366-A-5 10.5 IFT57
29 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 10.5 HNF1B
30 Decreased shRNA abundance (Z-score < -2) GR00366-A-77 10.5 FXYD2 HNF1B
31 Decreased shRNA abundance (Z-score < -2) GR00366-A-8 10.5 HNF1B
32 Decreased shRNA abundance (Z-score < -2) GR00366-A-80 10.5 HNF1B
33 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 10.5 FXYD2
34 Decreased shRNA abundance (Z-score < -2) GR00366-A-99 10.5 FXYD2
35 Increased shRNA abundance (Z-score > 2) GR00366-A-10 9.68 IFT57
36 Increased shRNA abundance (Z-score > 2) GR00366-A-106 9.68 RAB7A
37 Increased shRNA abundance (Z-score > 2) GR00366-A-108 9.68 SORD
38 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.68 SORD
39 Increased shRNA abundance (Z-score > 2) GR00366-A-137 9.68 IFT57
40 Increased shRNA abundance (Z-score > 2) GR00366-A-175 9.68 RAB7A
41 Increased shRNA abundance (Z-score > 2) GR00366-A-196 9.68 RAB7A
42 Increased shRNA abundance (Z-score > 2) GR00366-A-198 9.68 SORD
43 Increased shRNA abundance (Z-score > 2) GR00366-A-208 9.68 IFT57
44 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.68 IFT57
45 Increased shRNA abundance (Z-score > 2) GR00366-A-215 9.68 IFT57
46 Increased shRNA abundance (Z-score > 2) GR00366-A-28 9.68 RAB7A
47 Increased shRNA abundance (Z-score > 2) GR00366-A-36 9.68 RAB7A
48 Increased shRNA abundance (Z-score > 2) GR00366-A-39 9.68 RAB7A
49 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.68 IFT57
50 Increased shRNA abundance (Z-score > 2) GR00366-A-44 9.68 RAB7A

MGI Mouse Phenotypes related to Hypomagnesemia 2, Renal:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 renal/urinary system MP:0005367 9.02 AQP1 CLDN16 GNAS GRHPR HNF1B

Drugs & Therapeutics for Hypomagnesemia 2, Renal

Search Clinical Trials , 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 Hypomagnesemia 2 29 FXYD2

Anatomical Context for Hypomagnesemia 2, Renal

Publications for Hypomagnesemia 2, Renal

Articles related to Hypomagnesemia 2, Renal:

# Title Authors PMID Year
1
Recurrent FXYD2 p.Gly41Arg mutation in patients with isolated dominant hypomagnesaemia. 57 6
25765846 2015
2
Renal magnesium wasting in two families with autosomal dominant inheritance. 6 57
3298795 1987
3
Exclusion of mutations in FXYD2, CLDN16 and SLC12A3 in two families with primary renal Mg2+ loss. 57
12584272 2003
4
Distinct regulatory effects of the Na,K-ATPase gamma subunit. 6
11929868 2002
5
Genetic heterogeneity in familial renal magnesium wasting. 57
11836293 2002
6
Dominant isolated renal magnesium loss is caused by misrouting of the Na(+),K(+)-ATPase gamma-subunit. 57
11062458 2000
7
Hereditary isolated renal magnesium loss maps to chromosome 11q23. 57
9915957 1999
8
Disorders of renal magnesium handling explain renal magnesium transport. 54
17918133 2007
9
Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement. 61
17033971 2006
10
Pearson's syndrome presenting with Fanconi syndrome. 61
8883332 1996

Variations for Hypomagnesemia 2, Renal

ClinVar genetic disease variations for Hypomagnesemia 2, Renal:

6 (show all 23)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.121G>A (p.Gly41Arg) SNV Pathogenic 7684 rs28938168 GRCh37: 11:117693139-117693139
GRCh38: 11:117822424-117822424
2 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.36C>G (p.Pro12=) SNV Uncertain significance 880461 GRCh37: 11:117693422-117693422
GRCh38: 11:117822707-117822707
3 CNNM2 NM_017649.5(CNNM2):c.*873G>A SNV Uncertain significance 298664 rs886046678 GRCh37: 10:104837810-104837810
GRCh38: 10:103078053-103078053
4 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.*188C>T SNV Uncertain significance 302514 rs886047704 GRCh37: 11:117690906-117690906
GRCh38: 11:117820191-117820191
5 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.*124T>A SNV Uncertain significance 302516 rs756608243 GRCh37: 11:117690970-117690970
GRCh38: 11:117820255-117820255
6 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.*149A>G SNV Uncertain significance 878676 GRCh37: 11:117690945-117690945
GRCh38: 11:117820230-117820230
7 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.183C>T (p.Ile61=) SNV Likely benign 302523 rs201669990 GRCh37: 11:117691405-117691405
GRCh38: 11:117820690-117820690
8 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.*176T>G SNV Benign 302515 rs11999 GRCh37: 11:117690918-117690918
GRCh38: 11:117820203-117820203
9 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.76G>A (p.Val26Ile) SNV Benign 302524 rs149878562 GRCh37: 11:117693184-117693184
GRCh38: 11:117822469-117822469
10 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.*1C>T SNV Benign 302521 rs869789 GRCh37: 11:117691386-117691386
GRCh38: 11:117820671-117820671
11 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.*78C>A SNV Benign 302518 rs114952534 GRCh37: 11:117691016-117691016
GRCh38: 11:117820301-117820301
12 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.-10A>G SNV Benign 302527 rs12279985 GRCh37: 11:117695403-117695403
GRCh38: 11:117824688-117824688
13 FXYD2 , FXYD6-FXYD2 NM_021603.4(FXYD2):c.20-2040C>T SNV Benign 368933 rs12273102 GRCh37: 11:117695472-117695472
GRCh38: 11:117824757-117824757
14 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.*105C>T SNV Benign 302517 rs78017409 GRCh37: 11:117690989-117690989
GRCh38: 11:117820274-117820274
15 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.6+6C>A SNV Benign 302520 rs11827585 GRCh37: 11:117691375-117691375
GRCh38: 11:117820660-117820660
16 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.28G>A (p.Gly10Ser) SNV Benign 302526 rs146614981 GRCh37: 11:117693430-117693430
GRCh38: 11:117822715-117822715
17 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.198G>T (p.Pro66=) SNV Benign 724848 rs149353193 GRCh37: 11:117691390-117691390
GRCh38: 11:117820675-117820675
18 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.126C>T (p.Leu42=) SNV Benign 719221 rs144279659 GRCh37: 11:117693134-117693134
GRCh38: 11:117822419-117822419
19 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.90C>T (p.Gly30=) SNV Benign 879279 GRCh37: 11:117693170-117693170
GRCh38: 11:117822455-117822455
20 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.*215G>A SNV Benign 302513 rs41304349 GRCh37: 11:117690879-117690879
GRCh38: 11:117820164-117820164
21 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.*71G>A SNV Benign 302519 rs565539331 GRCh37: 11:117691023-117691023
GRCh38: 11:117820308-117820308
22 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.45C>T (p.Asp15=) SNV Benign 302525 rs35705701 GRCh37: 11:117693413-117693413
GRCh38: 11:117822698-117822698
23 FXYD2 , FXYD6-FXYD2 NM_001680.5(FXYD2):c.195G>A (p.Glu65=) SNV Benign 302522 rs144519777 GRCh37: 11:117691393-117691393
GRCh38: 11:117820678-117820678

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

72
# Symbol AA change Variation ID SNP ID
1 FXYD2 p.Gly41Arg VAR_013280 rs28938168

Expression for Hypomagnesemia 2, Renal

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

Pathways for Hypomagnesemia 2, Renal

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

# Super pathways Score Top Affiliating Genes
1 11.1 GNAS AQP1
2 10.88 GNAS FXYD2
3 10.75 GNAS FXYD2 AQP1
4 10.32 FXYD2 AQP1

GO Terms for Hypomagnesemia 2, Renal

Cellular components related to Hypomagnesemia 2, Renal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.1 SORD RAB7A GRHPR GNAS FXYD2 AQP1

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

# Name GO ID Score Top Affiliating Genes
1 response to drug GO:0042493 9.43 SORD HNF1B GNAS
2 renal water homeostasis GO:0003091 9.16 GNAS AQP1
3 excretion GO:0007588 8.96 GRHPR CLDN16
4 regulation of ion transport GO:0043269 8.62 FXYD6-FXYD2 FXYD2

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

# Name GO ID Score Top Affiliating Genes
1 NAD binding GO:0051287 8.96 SORD GRHPR
2 ion channel regulator activity GO:0099106 8.62 FXYD6-FXYD2 FXYD2

Sources for Hypomagnesemia 2, Renal

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