HYP
MCID: XLN002
MIFTS: 62

X-Linked Hypophosphatemia (HYP) malady

Genetic diseases, Rare diseases, Nephrological diseases, Bone diseases, Endocrine diseases, Fetal diseases categories

Summaries for X-Linked Hypophosphatemia

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9Disease Ontology, 44NIH Rare Diseases, 66Wikipedia, 48OMIM, 20GeneReviews, 34MalaCards
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NIH Rare Diseases:44 Hypophosphatemic rickets (previously called vitamin d-resistant rickets) is aĀ disorder in which the bones become painfully soft and bend easily because the blood contains low levels of phosphate and has inadequate amounts of the active form of vitamin d.Ā the conditionĀ can be caused by mutations in the phosphate-regulating endopeptidase gene, also known as the phex gene and is nearly always inherited. the aim of treatment is to raise phosphate levels in the blood, which will promote normal bone formation. phosphate can be taken by mouth and should be combined with calcitriol, the activated form of vitamin d. last updated: 9/17/2009

MalaCards: X-Linked Hypophosphatemia, also known as hypophosphatemic rickets, is related to hypophosphatemic rickets with hypercalciuria and hypophosphatemia, and has symptoms including mutiple fractures/bone fragility, hearing loss/hypoacusia/deafness and short stature/dwarfism/nanism. An important gene associated with X-Linked Hypophosphatemia is PHEX (phosphate regulating endopeptidase homolog, X-linked), and among its related pathways are FGFR ligand binding and activation and Insulin receptor signalling cascade. The compounds chloride and hydroxyapatite have been mentioned in the context of this disorder. Affiliated tissues include bone and kidney, and related mouse phenotypes are craniofacial and digestive/alimentary.

Disease Ontology:9 A metal metabolism disorder that results from the inactivation of hormone-like substances (phosphatonins) that promote phosphate excretion which has material basis in a x-linked mutation in the phex gene.

Wikipedia:66 X-linked hypophosphatemia (XLH), also called X-linked dominant hypophosphatemic rickets, X-linked... more...

Description from OMIM:48 241520,613312,300554,193100,307800

GeneReviews summary for rickets-xlh

Aliases & Classifications for X-Linked Hypophosphatemia

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9Disease Ontology, 10diseasecard, 20GeneReviews, 44NIH Rare Diseases, 21GeneTests, 48OMIM, 11DISEASES, 46Novoseek, 50Orphanet, 63UMLS, 36MeSH, 60SNOMED-CT via Orphanet, 27ICD10 via Orphanet
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Classifications:



Characteristics (Orphanet epidemiological data):

50
x-linked hypophosphatemia:
Inheritance: X-linked dominant; Prevalence: 1-9/100000; Age of onset: Childhood; Age of death: Normal


Aliases & Descriptions:

x-linked hypophosphatemia 9 20 11 50
hypophosphatemic rickets 10 44 21 48
hypophosphatemia, vitamin d-resistant rickets 9 44
hypophosphatemic rickets, x-linked dominant 10 48
vitamin d-resistant rickets, x-linked 9 44
x-linked hypophosphatemic rickets 20 50
hypophosphatemia, x-linked 44 21
xlh 44 50
hypophosphatemic rickets x-linked dominant 9
familial hypophosphatemic bone disease 63
x-linked vitamin d-resistant rickets 20
rickets, vitamin d-resistant 9
rickets, hypophosphatemic 9
rickets hypophosphatemic 46
xlhr 20
hyp 44


External Ids:

Disease Ontology9 DOID:0050445
MeSH36 D053098
SNOMED-CT via Orphanet60 82236004
ICD10 via Orphanet27 E83.3

Related Diseases for X-Linked Hypophosphatemia

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18GeneCards, 19GeneDecks
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Diseases related to X-Linked Hypophosphatemia via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 66)
idRelated DiseaseScoreTop Affiliating Genes
1hypophosphatemic rickets with hypercalciuria31.4SLC34A3
2hypophosphatemia31.4FGF23, SLC34A1, SLC34A3, PHEX, CLCN5, DMP1
3rickets30.7CLCN5, DMP1, FGF23, SLC34A3, PHEX
4nephrocalcinosis30.6CLCN5, PHEX, SLC34A3, SLC34A1
5osteomalacia30.5DMP1, KL, PHEX, SLC34A3, FGF23
6hyperparathyroidism30.5KL, PHEX, FGF23
7nephrolithiasis30.4FGF23, SLC34A1, CLCN5, SLC34A3
8hypophosphatemic rickets, autosomal dominant30.3FGF23, PHEX
9hyperphosphatemic familial tumoral calcinosis30.2FGF23, KL
10osteoporosis30.2KL, FGF23
11hyperphosphatemia30.0SLC34A1, FGF23, KL
12hereditary hypophosphatemic rickets with hypercalciuria10.8
13rickets, vitamin d-resistant, type iia10.5
14hypophosphatemic rickets, autosomal recessive 210.5
15epidermal nevus10.5
16hereditary hypophosphatemic rickets10.4
17oncogenic osteomalacia10.4
18dent's disease10.4
19hypophosphatemic rickets, ar10.4
20hypophosphatemic rickets and hyperparathyroidism10.4
21enthesopathy10.3
22mccune albright syndrome10.3
23fanconi syndrome10.3
24craniosynostosis10.3
25synostosis10.3
26hypophosphatemic rickets, autosomal recessive 110.3
27vitamin d-dependent rickets type i10.3
28renal tubular acidosis10.2
29hypophosphatasia10.2
30paraplegia10.2
31periodontitis10.2
32dwarfism10.2
33klinefelter's syndrome10.2
34aggressive periodontitis10.2
35osteopetrosis10.2
36kallmann syndrome10.2
37arterial calcification of infancy10.2
38osteogenesis imperfecta10.2
39tyrosinemia type i10.2
40fibrous dysplasia10.2
41papilledema10.2
42respiratory failure10.2
43rhabdomyosarcoma10.2
44aminoaciduria10.2
45familial glucocorticoid deficiency10.2
46fanconi bickel syndrome10.2
47linear nevus sebaceous syndrome10.2
48mitochondrial complex i deficiency10.2
49opsismodysplasia10.2
50phacomatosis pigmentokeratotica10.2

Graphical network of the top 20 diseases related to X-Linked Hypophosphatemia:



Diseases related to x-linked hypophosphatemia

Symptoms for X-Linked Hypophosphatemia

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48OMIM, 50Orphanet
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Symptoms by clinical synopsis from OMIM:

300554

Clinical features from OMIM:

241520,613312,300554,193100,307800

Symptoms:

50 (show all 15)
  • mutiple fractures/bone fragility
  • hearing loss/hypoacusia/deafness
  • short stature/dwarfism/nanism
  • enthesis anomaly/inflammation/enthesitis/enthesopathy
  • osteoarthritis
  • dense/thickened skull/calvarium/cranial/facial hyperostosis
  • x-linked dominant inheritance
  • hypophosphatemia
  • joint/articular deformation
  • metaphyseal anomaly
  • bone pain
  • osteoporosis/osteopenia/demineralisation/osteomalacia/rickets
  • genu varum
  • abnormal erosion/resorption of teeth/odontolysis
  • enamel anomaly

Drugs & Therapeutics for X-Linked Hypophosphatemia

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6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials, 63UMLS, 42NDF-RT
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Approved drugs:

Search CenterWatch for X-Linked Hypophosphatemia

Drug clinical trials:

Search ClinicalTrials for X-Linked Hypophosphatemia

Search NIH Clinical Center for X-Linked Hypophosphatemia

Search CenterWatch for X-Linked Hypophosphatemia

Genetic Tests for X-Linked Hypophosphatemia

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21GeneTests
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Genetic tests related to X-Linked Hypophosphatemia:

id Genetic test Affiliating Genes
1 X-Linked Hypophosphatemia21 PHEX
2 Hypophosphatemic Rickets Multi-Gene Panels21

Anatomical Context for X-Linked Hypophosphatemia

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32LifeMap Discoveryā„¢, 34MalaCards
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MalaCards organs/tissues related to X-Linked Hypophosphatemia:

34
Bone, Kidney

LifeMap Discovery
The database of embryonic development, stem cell research and regenerative medicine

Cells/anatomical compartments in embryo or adult related to X-Linked Hypophosphatemia:
id TissueAnatomical CompartmentCell Relevance
1 KidneyProximal TubuleProximal Tubule Cells Potential therapeutic candidate, affected by disease

Animal Models for X-Linked Hypophosphatemia or affiliated genes

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38MGI
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MGI Mouse Phenotypes related to X-Linked Hypophosphatemia:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053829.1DMP1, PHEX, CLCN5
2MP:00053818.5KL, PHEX, SLC34A3, FGF23
3MP:00053718.5KL, DMP1, PHEX, FGF23
4MP:00053677.5KL, PHEX, SLC34A3, SLC34A1, FGF23, CLCN5
5MP:00053787.5FGF23, SLC34A1, SLC34A3, PHEX, KL
6MP:00053767.4SLC34A3, CLCN5, KL, PHEX, SLC34A1, FGF23
7MP:00053906.9FGF23, DMP1, CLCN5, KL, PHEX, SLC34A3

Publications for X-Linked Hypophosphatemia

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53PubMed
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Articles related to X-Linked Hypophosphatemia:

(show top 50)    (show all 94)
idTitleAuthorsYear
1
High bone mineral apparent density in children with X-linked hypophosphatemia. (23389694)
2013
2
Dosage effect of a Phex mutation in a murine model of X-linked hypophosphatemia. (23700148)
2013
3
Iron and fibroblast growth factor 23 in X-linked hypophosphatemia. (24325979)
2013
4
MEPE-derived ASARM peptide inhibits odontogenic differentiation of dental pulp stem cells and impairs mineralization in tooth models of X-linked hypophosphatemia. (23451077)
2013
5
Calcitonin administration in X-linked hypophosphatemia. (21524226)
2011
6
Circulating levels of soluble klotho and FGF23 in X-linked hypophosphatemia: circadian variance, effects of treatment, and relationship to parathyroid status. (20685863)
2010
7
Autism and X-linked hypophosphatemia: A possible association? (20838491)
2010
8
X-linked hypophosphatemia: dental and histologic findings. (16480608)
2006
9
Role of prostaglandins in the pathogenesis of X-linked hypophosphatemia. (16721588)
2006
10
Role of matrix extracellular phosphoglycoprotein in the pathogenesis of X-linked hypophosphatemia. (15843468)
2005
11
Anthropometric characteristics of X-linked hypophosphatemia. (15057978)
2004
12
New intragenic deletions in the Phex gene clarify X-linked hypophosphatemia-related abnormalities in mice. (15029877)
2004
13
Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. (12890852)
2003
14
Effect of GH replacement therapy in two male siblings with combined X-linked hypophosphatemia and partial GH deficiency. (14514346)
2003
15
An ethyl-nitrosourea-induced point mutation in phex causes exon skipping, x-linked hypophosphatemia, and rickets. (12414538)
2002
16
Thiazide diuretics arrest the progression of nephrocalcinosis in children with X-linked hypophosphatemia. (11433085)
2001
17
X-linked hypophosphatemia in Polish patients. 1. Mutations in the PHEX gene. (14564077)
2000
18
Effect of dipyridamole on serum and urinary phosphate in X-linked hypophosphatemia. (11095012)
2000
19
PHEXdb, a locus-specific database for mutations causing X-linked hypophosphatemia. (10874297)
2000
20
PHEX expression in parathyroid gland and parathyroid hormone dysregulation in X-linked hypophosphatemia. (10460513)
1999
21
Evidence for Phex haploinsufficiency in murine X-linked hypophosphatemia. (10087298)
1999
22
Mutational analysis of PHEX gene in X-linked hypophosphatemia. (9768674)
1998
23
The effect of recombinant human growth hormone in children with X-linked hypophosphatemia. (9346990)
1997
24
New insights into X-linked hypophosphatemia. (9051349)
1997
25
Pex gene deletions in Gy and Hyp mice provide mouse models for X-linked hypophosphatemia. (9063736)
1997
26
Paraplegia due to ossification of ligamenta flava in X-linked hypophosphatemia. A case report. (9089946)
1997
27
Phosphate transport in renal cell cultures of gy mice: evidence of a single defect in X-linked hypophosphatemia. (9249598)
1997
28
X-linked hypophosphatemia: effects of treatment with recombinant human growth hormone. (9323282)
1997
29
Whole-body bone scan findings in X-linked hypophosphatemia. (8744188)
1996
30
X-linked hypophosphatemia: a search for gender, race, anticipation, or parent of origin effects on disease expression in children. (8923863)
1996
31
Nephrocalcinosis is associated with renal tubular acidosis in children with X-linked hypophosphatemia. (8545232)
1996
32
Nephrocalcinosis in X-linked hypophosphatemia: effect of treatment versus disease. (7794712)
1995
33
Stimulation of growth hormone secretion in children with X-linked hypophosphatemia. (8747120)
1995
34
Chromosomal localization of the human renal sodium phosphate transporter to chromosome 5: implications for X-linked hypophosphatemia. (8047391)
1994
35
Nocturnal hyperparathyroidism: a frequent feature of X-linked hypophosphatemia. (8200940)
1994
36
Enthesopathy as the presenting feature of X-linked hypophosphatemia. A case report. (8498190)
1993
37
X-Linked Hypophosphatemia (22319799)
1993
38
Effects of calcitriol and phosphorus therapy on the growth of patients with X-linked hypophosphatemia. (8473393)
1993
39
X-linked hypophosphatemia: an appreciation of a classic paper and a survey of progress since 1958. (1851532)
1991
40
X-linked hypophosphatemia: skeletal mass in adults assessed by histomorphometry, computed tomography, and absorptiometry. (1986592)
1991
41
X-linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features. (2539609)
1989
42
Calcitonin stimulation of renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity in hypophosphatemic mice. Evidence that the regulation of calcitriol production is not universally abnormal in X-linked hypophosphatemia. (3793922)
1987
43
Audiometric evidence for two forms of X-linked hypophosphatemia in humans, apparent counterparts of Hyp and Gy mutations in mouse. (3425609)
1987
44
The Gy mutation: another cause of X-linked hypophosphatemia in mouse. (3460077)
1986
45
X-linked hypophosphatemia (familial or sex-linked vitamin-D-resistant rickets). X-linked hypophosphatemic (Hyp) mice. (2982272)
1985
46
Renal adaptation to phosphate deprivation in the Hyp mouse with X-linked hypophosphatemia. (476527)
1979
47
The defect in transcellular transport of phosphate in the nephron is located in brush-border membranes in X-linked hypophosphatemia (Hyp mouse model). (566613)
1978
48
Occurrence of hyperparathyroidism in children with X-linked hypophosphatemia under treatment with vitamin D and phsophate. (899930)
1977
49
Familial forms of vitamin D-resistant rickets revisited. X-linked hypophosphatemia and autosomal recessive vitamin D dependency. (187056)
1976
50
Serum parathyroid hormone in X-linked hypophosphatemia. (5315247)
1971

Variations for X-Linked Hypophosphatemia

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65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar)
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UniProtKB/Swiss-Prot genetic disease variations for X-Linked Hypophosphatemia:

65 (show all 31)
id Symbol AA change Variation ID SNP ID
1CLCN5p.Ser244LeuVAR_001618
2PHEXp.Cys77SerVAR_006738
3PHEXp.Cys85TyrVAR_006739
4PHEXp.Leu138ProVAR_006740
5PHEXp.Arg166CysVAR_006741
6PHEXp.Phe252SerVAR_006742
7PHEXp.Met253IleVAR_006743
8PHEXp.Pro534LeuVAR_006744
9PHEXp.Gly579ArgVAR_006745
10PHEXp.Gly579ValVAR_006746
11PHEXp.Phe80SerVAR_010616
12PHEXp.Cys85PheVAR_010617
13PHEXp.Cys85ArgVAR_010618
14PHEXp.Ser141ProVAR_010619
15PHEXp.Cys142PheVAR_010620
16PHEXp.Leu160ArgVAR_010621
17PHEXp.Asp237GlyVAR_010622
18PHEXp.Tyr317PheVAR_010623
19PHEXp.Trp530CysVAR_010626
20PHEXp.Leu555ProVAR_010627
21PHEXp.Arg567ProVAR_010628
22PHEXp.Ala573AspVAR_010629
23PHEXp.Gln621ArgVAR_010630
24PHEXp.Arg651ProVAR_010631
25PHEXp.Asn680LysVAR_010633
26PHEXp.Cys693TyrVAR_010634
27PHEXp.Ala720ThrVAR_010635
28PHEXp.Phe731TyrVAR_010636
29PHEXp.Cys733SerVAR_010637
30PHEXp.Cys746TrpVAR_010638
31PHEXp.Trp749ArgVAR_010639

Clinvar genetic disease variations for X-Linked Hypophosphatemia:

1 (show all 12)
id Gene Name Type Significance SNP ID Assembly Location
1PHEXPHEX, 2-BP DEL, 675TCdeletionPathogenic
2PHEXPHEX, IVS1AS, G-A, -1single nucleotide variantPathogenic
3PHEXPHEX, IVS1AS, G-C, -1single nucleotide variantPathogenic
4PHEXNM_000444.5(PHEX): c.830T> A (p.Leu277Ter)single nucleotide variantPathogenicrs137853268GRCh37Chr X, 22112198: 22112198
5PHEXNM_000444.5(PHEX): c.254G> A (p.Cys85Tyr)single nucleotide variantPathogenicrs137853269GRCh37Chr X, 22065234: 22065234
6PHEXNM_000444.5(PHEX): c.755T> C (p.Phe252Ser)single nucleotide variantPathogenicrs267606945GRCh37Chr X, 22112123: 22112123
7PHEXNM_000444.5(PHEX): c.1664T> C (p.Leu555Pro)single nucleotide variantPathogenicrs137853270GRCh37Chr X, 22231039: 22231039
8PHEXPHEX, A-G, NT-429single nucleotide variantPathogenic
9PHEXPHEX, IVS7, +1268, G-Tsingle nucleotide variantPathogenic
10PHEXNM_000444.5(PHEX): c.1699C> T (p.Arg567Ter)single nucleotide variantPathogenicrs137853271GRCh37Chr X, 22231074: 22231074
11PHEXPHEX, IVS4, T-C, +6single nucleotide variantPathogenic
12CLCN5NM_001127899.3(CLCN5): c.941C> T (p.Ser314Leu)single nucleotide variantPathogenicrs151340626GRCh37Chr X, 49850644: 49850644

Expression for genes affiliated with X-Linked Hypophosphatemia

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2BioGPS, 16Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with X-Linked Hypophosphatemia

Search GEO for disease gene expression data for X-Linked Hypophosphatemia.

Pathways for genes affiliated with X-Linked Hypophosphatemia

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51PathCards, 56Reactome, 61Thomson Reuters, 39NCBI BioSystems Database
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Pathways related to X-Linked Hypophosphatemia according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.5FGF23, KL
2
Show member pathways
9.5FGF23, KL
3
Show member pathways
8.7SLC34A1, SLC34A3, CLCN5

Compounds for genes affiliated with X-Linked Hypophosphatemia

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46Novoseek, 62Tocris Bioscience, 25HMDB, 12DrugBank, 52PharmGKB
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Compounds related to X-Linked Hypophosphatemia according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1chloride469.2SLC34A1, CLCN5
2hydroxyapatite469.1FGF23, DMP1
3phosphorus468.9PHEX, SLC34A1, FGF23
41,25 dihydroxy vitamin d3468.8FGF23, SLC34A1, PHEX
5calcitriol46 62 25 1211.7FGF23, SLC34A1, PHEX
6vitamin d468.3DMP1, PHEX, SLC34A1, FGF23
7calcium46 52 25 129.9FGF23, DMP1, CLCN5, KL, PHEX, SLC34A3

GO Terms for genes affiliated with X-Linked Hypophosphatemia

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17Gene Ontology
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Cellular components related to X-Linked Hypophosphatemia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1integral component of plasma membraneGO:0058878.3SLC34A1, PHEX, KL, CLCN5

Biological processes related to X-Linked Hypophosphatemia according to GeneCards/GeneDecks:

(show all 13)
idNameGO IDScoreTop Affiliating Genes
1positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathwayGO:0900809.8KL, FGF23
2cellular phosphate ion homeostasisGO:0306439.7FGF23, SLC34A3
3phosphatidylinositol-mediated signalingGO:0480159.6KL, FGF23
4insulin receptor signaling pathwayGO:0082869.6KL, FGF23
5epidermal growth factor receptor signaling pathwayGO:0071739.5FGF23, KL
6phosphate ion homeostasisGO:0550629.5SLC34A1, FGF23
7fibroblast growth factor receptor signaling pathwayGO:0085439.4FGF23, KL
8phosphate ion transportGO:0068179.4SLC34A1, SLC34A3
9sodium ion transportGO:0068149.3SLC34A3, SLC34A1
10ossificationGO:0015039.2SLC34A1, DMP1
11Fc-epsilon receptor signaling pathwayGO:0380959.2KL, FGF23
12ion transportGO:0068119.1SLC34A3, SLC34A1
13transmembrane transportGO:0550858.9CLCN5, SLC34A3, SLC34A1

Molecular functions related to X-Linked Hypophosphatemia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1sodium-dependent phosphate transmembrane transporter activityGO:0153219.1SLC34A1, SLC34A3

Products for genes affiliated with X-Linked Hypophosphatemia

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Sources for X-Linked Hypophosphatemia

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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet