HPP
MCID: HYP035
MIFTS: 61

Hypophosphatasia (HPP)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Oral diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Hypophosphatasia

MalaCards integrated aliases for Hypophosphatasia:

Name: Hypophosphatasia 12 73 25 20 43 58 36 29 54 6 44 15 39 70
Phosphoethanolaminuria 20 43 58
Deficiency of Alkaline Phosphatase 12 43
Childhood Hypophosphatasia 12 70
Hypophosphatasia, Childhood 44
Infantile Hypophosphatasia 70
Hypophospatasia, Childhood 12
Phosphoethanol-Aminuria 20
Hypophosphatasia Mild 20
Rathburn Disease 20
Rathbun Disease 58
Hpp 58

Characteristics:

Orphanet epidemiological data:

58
hypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: 1-9/1000000 (Europe),1-9/1000000 (France),1-9/1000000 (United Kingdom),1-9/1000000 (Ireland),1-9/1000000 (Japan); Age of onset: All ages; Age of death: any age;

Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:14213
KEGG 36 H00213
NCIt 50 C26798
SNOMED-CT 67 30174008 70848009
ICD10 32 E83.39
MESH via Orphanet 45 D007014
ICD10 via Orphanet 33 E83.3
UMLS via Orphanet 71 C0020630
Orphanet 58 ORPHA436
UMLS 70 C0020630 C0220743 C0268412

Summaries for Hypophosphatasia

MedlinePlus Genetics : 43 Hypophosphatasia is an inherited disorder that affects the development of bones and teeth. This condition disrupts a process called mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding.The signs and symptoms of hypophosphatasia vary widely and can appear anywhere from before birth to adulthood. The most severe forms of the disorder tend to occur before birth and in early infancy. Hypophosphatasia weakens and softens the bones, causing skeletal abnormalities similar to another childhood bone disorder called rickets. Affected infants are born with short limbs, an abnormally shaped chest, and soft skull bones. Additional complications in infancy include poor feeding and a failure to gain weight, respiratory problems, and high levels of calcium in the blood (hypercalcemia), which can lead to recurrent vomiting and kidney problems. These complications are life-threatening in some cases.The forms of hypophosphatasia that appear in childhood or adulthood are typically less severe than those that appear in infancy. Early loss of primary (baby) teeth is one of the first signs of the condition in children. Affected children may have short stature with bowed legs or knock knees, enlarged wrist and ankle joints, and an abnormal skull shape. Adult forms of hypophosphatasia are characterized by a softening of the bones known as osteomalacia. In adults, recurrent fractures in the foot and thigh bones can lead to chronic pain. Affected adults may lose their secondary (adult) teeth prematurely and are at increased risk for joint pain and inflammation.The mildest form of this condition, called odontohypophosphatasia, only affects the teeth. People with this disorder typically experience abnormal tooth development and premature tooth loss, but do not have the skeletal abnormalities seen in other forms of hypophosphatasia.

MalaCards based summary : Hypophosphatasia, also known as phosphoethanolaminuria, is related to hypophosphatasia, childhood and hypophosphatasia, infantile, and has symptoms including seizures, constipation and vomiting. An important gene associated with Hypophosphatasia is ALPL (Alkaline Phosphatase, Biomineralization Associated), and among its related pathways/superpathways are Folate biosynthesis and NAD metabolism. The drugs Immunoglobulin G and Immunoglobulins have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and kidney, and related phenotypes are bowing of the long bones and abnormality of the dentition

Disease Ontology : 12 A syndrome characterized by disruption of mineralization of bones and teeth that has material basis in mutation in ALPL on chromosome 1p36.12.

GARD : 20 Hypophosphatasia (HPP) is a genetic condition that causes abnormal development of the bones and teeth. The severity of HPP can vary widely, from fetal death to fractures that don't begin until adulthood. Signs and symptoms may include poor feeding and respiratory problems in infancy; short stature ; weak and soft bones; short limbs; other skeletal abnormalities; and hypercalcemia. Complications can be life-threatening. The mildest form of the condition, called odontohypophosphatasia, only affects the teeth. HPP is caused by mutations in the ALPL gene. Perinatal (onset before birth) and infantile HPP are inherited in an autosomal recessive manner. The milder forms, especially adult forms and odontohypophosphatasia, may be inherited in an autosomal recessive or autosomal dominant manner. While treatment has always been symptomatic and supportive, recently an enzyme replacement therapy (ERT) called asfotase alfa has been show to improve bone manifestations people with childhood onset HPP and has been approved by the FDA.

KEGG : 36 Hypophosphatasia is an autosomal recessive disorder caused by deficiency of alkaline phosphatase activity and characterized by defective bone and teeth mineralization.

Wikipedia : 73 Hypophosphatasia (also called deficiency of alkaline phosphatase or phosphoethanolaminuria and sometimes... more...

GeneReviews: NBK1150

Related Diseases for Hypophosphatasia

Diseases in the Hypophosphatasia family:

Hypophosphatasia, Adult Hypophosphatasia, Infantile

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

(show top 50) (show all 212)
# Related Disease Score Top Affiliating Genes
1 hypophosphatasia, childhood 32.8 PTH PHOSPHO1 ENPP1 ALPL
2 hypophosphatasia, infantile 32.4 PNPO PHOSPHO1 KHDRBS3 ENPP1 ALPP ALPL
3 hypophosphatasia, adult 32.0 PTH PHOSPHO1 KHDRBS3 ENPP1 ANKH ALPL
4 chondrocalcinosis 30.8 ENPP1 ANKH ALPL
5 craniosynostosis 30.6 RUNX2 PHEX ENPP1 ANKH ALPL
6 osteomalacia 30.5 PTH PHEX ENPP1 BGLAP ALPP ALPL
7 rickets 30.4 PTH PHEX ENPP1 DSPP BGLAP ALPP
8 periarthritis 30.3 PHOSPHO1 ENPP1 ANKH ALPL
9 root resorption 30.2 SPP1 RUNX2 DSPP
10 teeth, supernumerary 30.1 RUNX2 DSPP
11 hypophosphatemic rickets, x-linked recessive 30.0 PHEX ENPP1 DSPP
12 bone resorption disease 29.8 SPP1 RUNX2 PTH BGLAP
13 hyperostosis 29.8 SPP1 ANKH ALPL
14 cleidocranial dysplasia 29.8 SPP1 RUNX2 BGLAP ALPP ALPL
15 hyperparathyroidism 29.8 SLPI PTH PHEX BGLAP ALPP
16 hyperphosphatemia 29.7 SPP1 RUNX2 PTH PHEX BGLAP
17 calcinosis 29.7 SPP1 PHEX ENPP1 ANKH
18 chronic recurrent multifocal osteomyelitis 29.7 CCL27 BGLAP ALPL
19 renal osteodystrophy 29.7 SLPI PTH BGLAP
20 autoimmune lymphoproliferative syndrome 29.6 SPP1 ALPP ALPL ALPI ALPG
21 enthesopathy 29.6 PTH PHEX ENPP1 ANKH
22 secondary hyperparathyroidism 29.5 SLPI PTH PHEX BGLAP
23 uremia 29.5 SPP1 RUNX2 PTH ENPP1
24 pseudoxanthoma elasticum 29.5 SPP1 ENPP1 ANKH ALPL
25 brittle bone disorder 29.5 SPP1 RUNX2 PTH PHEX DSPP BGLAP
26 bone disease 29.4 SPP1 SLPI RUNX2 PTH PHEX BGLAP
27 metaphyseal chondrodysplasia, jansen type 29.4 PTH PHEX
28 hyperthyroidism 29.4 PTH BGLAP ALPP
29 primary hyperparathyroidism 29.4 PTH BGLAP ALPP
30 spondyloarthropathy 1 29.3 PTH BGLAP ANKH
31 ankylosis 29.3 RUNX2 PLCB4 PHOSPHO1 ENPP1 BGLAP ANKH
32 osteochondrodysplasia 29.2 SPP1 RUNX2 PTH PHEX DSPP BGLAP
33 kidney disease 29.2 SPP1 SLPI PTH ENPP1 BGLAP
34 arterial calcification of infancy 29.1 SPP1 PHOSPHO1 PHEX ENPP1 ANKH ALPL
35 hypophosphatemia 29.1 SPP1 PTH PHEX ENPP1 DSPP BGLAP
36 osteogenic sarcoma 29.1 SPP1 RUNX2 PTH BGLAP
37 hypophosphatemic rickets, x-linked dominant 29.0 SPP1 PTH PHEX ENPP1 DSPP BGLAP
38 chronic kidney disease 28.7 SPP1 SLPI RUNX2 PTH ENPP1 BGLAP
39 pyropoikilocytosis, hereditary 11.5
40 prenatal benign hypophosphatasia 11.0
41 multiple congenital anomalies-hypotonia-seizures syndrome 3 10.9
42 atelosteogenesis, type i 10.9
43 boomerang dysplasia 10.9
44 dentin dysplasia, type i 10.9
45 respiratory failure 10.4
46 nephrocalcinosis 10.4
47 pediatric ovarian germ cell tumor 10.3 PTH ALPP
48 pediatric ovarian dysgerminoma 10.3 PTH ALPP
49 suppurative periapical periodontitis 10.3 PHEX DSPP
50 seizure disorder 10.3

Graphical network of the top 20 diseases related to Hypophosphatasia:



Diseases related to Hypophosphatasia

Symptoms & Phenotypes for Hypophosphatasia

Human phenotypes related to Hypophosphatasia:

58 31 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 bowing of the long bones 58 31 hallmark (90%) Very frequent (99-80%) HP:0006487
2 abnormality of the dentition 58 31 hallmark (90%) Very frequent (99-80%) HP:0000164
3 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
4 feeding difficulties in infancy 58 31 hallmark (90%) Very frequent (99-80%) HP:0008872
5 abnormality of the metaphysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000944
6 failure to thrive in infancy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001531
7 emphysema 58 31 hallmark (90%) Very frequent (99-80%) HP:0002097
8 abnormality of the ribs 58 31 hallmark (90%) Very frequent (99-80%) HP:0000772
9 large fontanelles 58 31 hallmark (90%) Very frequent (99-80%) HP:0000239
10 narrow chest 58 31 hallmark (90%) Very frequent (99-80%) HP:0000774
11 skin dimple over apex of long bone angulation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001024
12 craniosynostosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001363
13 respiratory insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002093
14 anemia 58 31 frequent (33%) Frequent (79-30%) HP:0001903
15 irritability 58 31 frequent (33%) Frequent (79-30%) HP:0000737
16 recurrent fractures 58 31 frequent (33%) Frequent (79-30%) HP:0002757
17 hypercalcemia 58 31 frequent (33%) Frequent (79-30%) HP:0003072
18 seizure 31 frequent (33%) HP:0001250
19 hypotonia 31 frequent (33%) HP:0001252
20 seizures 58 Frequent (79-30%)
21 muscular hypotonia 58 Frequent (79-30%)
22 skin dimples 58 Very frequent (99-80%)

UMLS symptoms related to Hypophosphatasia:


seizures; constipation; vomiting; waddling gait; apnea; fever of unknown origin

GenomeRNAi Phenotypes related to Hypophosphatasia according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.62 PLCB4
2 Decreased viability GR00221-A-4 9.62 PLCB4
3 Decreased viability GR00240-S-1 9.62 DSPP
4 Decreased viability GR00249-S 9.62 ALPI ALPL ANKH ENPP1 PLCB4 PNPO
5 Decreased viability GR00381-A-1 9.62 ALPG DSPP SLPI
6 Decreased viability GR00386-A-1 9.62 ALPL ANKH KHDRBS3 RUNX2
7 Decreased viability GR00402-S-2 9.62 DSPP ENPP1
8 Decreased cell migration GR00055-A-1 8.96 ALPL PLCG1

MGI Mouse Phenotypes related to Hypophosphatasia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.8 ALPL ANKH ENPP1 PHEX PTH RUNX2
2 mortality/aging MP:0010768 9.8 ALPG ALPL ANKH ENPP1 KHDRBS3 PHEX
3 limbs/digits/tail MP:0005371 9.7 ALPL ANKH ENPP1 PHEX PHOSPHO1 PTH
4 skeleton MP:0005390 9.32 ALPL ANKH BGLAP ENPP1 PHEX PHOSPHO1

Drugs & Therapeutics for Hypophosphatasia

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


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Immunoglobulin G Phase 1, Phase 2
2 Immunoglobulins Phase 1, Phase 2
3 Immunologic Factors Phase 1, Phase 2
4 Antibodies Phase 1, Phase 2
5 Immunoglobulins, Intravenous Phase 1, Phase 2

Interventional clinical trials:

(show all 29)
# Name Status NCT ID Phase Drugs
1 A Multicenter, Post-Approval Clinical Study for Asfotase Alfa (Human Recombinant Tissue-nonspecific Alkaline Phosphatase Fusion Protein) Treatment for Patients With Hypophosphatasia (HPP) in Japan Completed NCT02531867 Phase 4
2 A Phase 4, Randomized, Multicenter, Open-Label, 2-Dosage Regimen, Safety and Tolerability, Efficacy, Pharmacokinetic, and Pharmacodynamic Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia Withdrawn NCT04189315 Phase 4 asfotase alfa
3 An Open-Label, Multicenter, Multinational Study of the Safety, Efficacy and Pharmacokinetics of Asfotase Alfa (Human Recombinant Tissue-nonspecific Alkaline Phosphatase Fusion Protein) in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP) Completed NCT01176266 Phase 2, Phase 3 asfotase alfa
4 A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of Asfotase Alfa in up to 10 Severely Affected Patients With for the Treatment of Severely Affected Patients With Infantile Hypophosphatasia (HPP) Completed NCT00744042 Phase 1, Phase 2
5 A Multicenter Study of the Safety and Efficacy of Asfotase Alfa (ALXN1215) (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Patients With Hypophosphatasia (HPP) Completed NCT02456038 Phase 2 Asfotase Alfa (ALXN1215)
6 A Randomized, Open-Label, Multicenter, Multinational, Dose-Ranging, Historical Control Study of the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Children With Hypophosphatasia (HPP) Completed NCT00952484 Phase 2
7 Extension Study of Protocol ENB-006-09 Evaluating the Long-term Safety and Efficacy of Asfotase Alfa (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Children With Hypophosphatasia (HPP) Completed NCT01203826 Phase 2
8 A Phase 2a, Randomized, Multicenter, Open-Label, Pharmacokinetic, and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia Completed NCT02797821 Phase 2 Asfotase alfa
9 A Randomized, Open-Label, Multicenter, Multinational, Dose-Ranging, Concurrent Control Study of the Safety, Efficacy, Pharmacokinetic of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Adolescents and Adults With Hypophosphatasia (HPP) Completed NCT01163149 Phase 2 asfotase alfa;asfotase alfa
10 An Open-label, Intra-patient Dose-escalation Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP). Completed NCT01406977 Phase 2 BPS804
11 Extension Study of ENB-0040 (Human Recombinant Tissue-Nonspecific Alkaline Phosphatase Fusion Protein) in Severely Affected Infants and Young Children With Hypophosphatasia (HPP) Completed NCT01205152 Phase 2
12 Single-Center, Case-Control Study of Safety, Efficacy and Pharmacokinetics of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) for Treatment of Hypophosphatasia in Children Withdrawn NCT00894075 Phase 2
13 A Multicenter, Open-Label, Dose Escalating Study of the Safety, Tolerability and Pharmacology of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP) Completed NCT00739505 Phase 1
14 An Open-label, Multicenter, Expanded Access Program for Asfotase Alfa (Human Recombinant Tissue-nonspecific Alkaline Phosphatase Fusion Protein) Treatment for Patients With Infantile- or Juvenile-onset Hypophosphatasia (HPP) Approved for marketing NCT02496689
15 A Retrospective, Non-interventional Epidemiologic Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP) Completed NCT01419028
16 Health Burden of Hypophosphatasia Completed NCT02751801
17 A Retrospective, Non-interventional, Epidemiologic Study of the Natural History of Patients With Juvenile-onset Hypophosphatasia (HPP) Completed NCT02104219
18 Non-interventional, Prospective, Single-center Investigation With Exploratory Data Analysis to Delineate the Variability and Frequency of Symptoms and Disease Manifestations in Adult HPP Patients Completed NCT02291497
19 A Single-Center, Non-interventional Substudy of ALX-HPP-502 to Assess Functional Natural History Data of Patients With Juvenile Historical Controls in ENB-006-09 Completed NCT02235493
20 Characterisation of Adult-Onset Hypophosphatasia Recruiting NCT02796885
21 Natural History Study of Adult and Pediatric Patients With Hypophosphatasia Recruiting NCT02237625
22 Circulating miRNAs and Bone Microstructure in Adults With Hypophosphatasia Recruiting NCT04018287
23 Coordination of Rare Diseases at Sanford Recruiting NCT01793168
24 Evaluation of Bone Architecture and Bone Strength in Adults With Hypophosphatasia (HPP) Active, not recruiting NCT04181164
25 Biomarker for Hypophosphatasia Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL Active, not recruiting NCT02603042
26 An Observational, Longitudinal Study to Evaluate and Monitor Physical Performance of Adults Treated With Asfotase Alfa for Pediatric-Onset Hypophosphatasia Enrolling by invitation NCT03418389
27 A Prospective Study to Evaluate the Patient Reported Quality of Life Prior to and After Strensiq® Treatment in Adults With Pediatric Onset Hypophosphatasia Enrolling by invitation NCT04195763 asfotase alfa
28 An Observational, Longitudinal, Prospective, Long-Term Registry Of Patients With Hypophosphatasia (HPP) Enrolling by invitation NCT02306720
29 Clinical Consequences of Adults Presenting With hyPophOsphatasia With Special Focus on Gait, Bone micRosTRucture And cognITion: The PORTRAIT Study Suspended NCT04222452

Search NIH Clinical Center for Hypophosphatasia

Cochrane evidence based reviews: hypophosphatasia

Genetic Tests for Hypophosphatasia

Genetic tests related to Hypophosphatasia:

# Genetic test Affiliating Genes
1 Hypophosphatasia 29 ALPL

Anatomical Context for Hypophosphatasia

MalaCards organs/tissues related to Hypophosphatasia:

40
Bone, Bone Marrow, Kidney, Lung, Skin, Neutrophil, Eye

Publications for Hypophosphatasia

Articles related to Hypophosphatasia:

(show top 50) (show all 1027)
# Title Authors PMID Year
1
Delayed transport of tissue-nonspecific alkaline phosphatase with missense mutations causing hypophosphatasia. 54 25 6 61
17719863 2007
2
Common mutations F310L and T1559del in the tissue-nonspecific alkaline phosphatase gene are related to distinct phenotypes in Japanese patients with hypophosphatasia. 6 25 54 61
15660230 2005
3
A molecular approach to dominance in hypophosphatasia. 61 54 6 25
11479741 2001
4
Intracellular retention and degradation of tissue-nonspecific alkaline phosphatase with a Gly317-->Asp substitution associated with lethal hypophosphatasia. 61 54 6 25
9618260 1998
5
Defective intracellular transport of tissue-nonspecific alkaline phosphatase with an Ala162-->Thr mutation associated with lethal hypophosphatasia. 6 25 54 61
9562633 1998
6
An asparagine at position 417 of tissue-nonspecific alkaline phosphatase is essential for its structure and function as revealed by analysis of the N417S mutation associated with severe hypophosphatasia. 61 25 6
23688511 2013
7
Enzyme-replacement therapy in life-threatening hypophosphatasia. 25 6 61
22397652 2012
8
Hypophosphatasia: nonlethal disease despite skeletal presentation in utero (17 new cases and literature review). 6 25 61
21713987 2011
9
Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles. 25 6 61
19500388 2009
10
Characterization of missense mutations and large deletions in the ALPL gene by sequencing and quantitative multiplex PCR of short fragments. 61 6 25
17253930 2006
11
Mild autosomal dominant hypophosphatasia: in utero presentation in two families. 25 6 61
10508980 1999
12
Correlations of genotype and phenotype in hypophosphatasia. 61 6 25
10332035 1999
13
Chronic recurrent multifocal osteomyelitis mimicked in childhood hypophosphatasia. 61 54 6
19335222 2009
14
Orodental phenotype and genotype findings in all subtypes of hypophosphatasia. 61 54 6
19232125 2009
15
How can calcium pyrophosphate crystals induce inflammation in hypophosphatasia or chronic inflammatory joint diseases? 54 61 6
18821074 2009
16
Autosomal recessive hypophosphatasia manifesting in utero with long bone deformity but showing spontaneous postnatal improvement. 61 54 6
18559907 2008
17
Functional assay of the mutant tissue-nonspecific alkaline phosphatase gene using U2OS osteoblast-like cells. 61 54 6
18455459 2008
18
A case of lethal hypophosphatasia providing new insights into the perinatal benign form of hypophosphatasia and expression of the ALPL gene. 6 54 61
17922851 2008
19
Hypophosphatasia. 61 6 54
18328985 2008
20
Mutations of the tissue non-specific alkaline phosphatase gene (TNAP) causing a non-lethal case of perinatal hypophosphatasia. 6 61 54
17409132 2007
21
Adult hypophosphatasia treated with teriparatide. 61 6 54
17213282 2007
22
[Hypophosphatasia: report of two affected girls with spontaneous improvement of skeletal defects]. 6 61 54
16583935 2005
23
Novel aggregate formation of a frame-shift mutant protein of tissue-nonspecific alkaline phosphatase is ascribed to three cysteine residues in the C-terminal extension. Retarded secretion and proteasomal degradation. 61 6 54
15794757 2005
24
Positive maternal serum triple test screening in severe early onset hypophosphatasia. 6 54 61
15300736 2004
25
[Childhood hypophosphatasia: a case report due to a novel mutation]. 6 61 54
15135428 2004
26
The mutant (F310L and V365I) tissue-nonspecific alkaline phosphatase gene from hypophosphatasia. 6 61 54
15137467 2004
27
Severe hypophosphatasia: characterization of fifteen novel mutations in the ALPL gene. 61 6 54
12815606 2003
28
Evidence of a founder effect for the tissue-nonspecific alkaline phosphatase (TNSALP) gene E174K mutation in hypophosphatasia patients. 61 54 6
12357339 2002
29
Kinetic characterization of hypophosphatasia mutations with physiological substrates. 6 61 54
12162492 2002
30
Glu274Lys/Gly309Arg mutation of the tissue-nonspecific alkaline phosphatase gene in neonatal hypophosphatasia associated with convulsions. 61 54 6
11999978 2002
31
Denaturing gradient gel electrophoresis analysis of the tissue nonspecific alkaline phosphatase isoenzyme gene in hypophosphatasia. 6 61 54
11855933 2002
32
Importance of deletion of T at nucleotide 1559 in the tissue-nonspecific alkaline phosphatase gene in Japanese patients with hypophosphatasia. 54 6 61
11810413 2002
33
Mutational analysis and functional correlation with phenotype in German patients with childhood-type hypophosphatasia. 6 54 61
11760847 2001
34
Perinatal hypophosphatasia: radiology, pathology and molecular biology studies in a family harboring a splicing mutation (648+1A) and a novel missense mutation (N400S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. 6 54 61
11745997 2001
35
Twelve novel mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL) in patients with various forms of hypophosphatasia. 54 6 61
11438998 2001
36
Possible interference between tissue-non-specific alkaline phosphatase with an Arg54-->Cys substitution and acounterpart with an Asp277-->Ala substitution found in a compound heterozygote associated with severe hypophosphatasia. 54 6 61
10839996 2000
37
Fifteen new mutations (-195C>T, L-12X, 298-2A>G, T117N, A159T, R229S, 997+2T>A, E274X, A331T, H364R, D389G, 1256delC, R433H, N461I, C472S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with hypophosphatasia. 54 61 6
10679946 2000
38
Characterization of eleven novel mutations (M45L, R119H, 544delG, G145V, H154Y, C184Y, D289V, 862+5A, 1172delC, R411X, E459K) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with severe hypophosphatasia. Mutations in brief no. 217. Online. 61 54 6
10094560 1999
39
Expression of the mutant (1735T-DEL) tissue-nonspecific alkaline phosphatase gene from hypophosphatasia patients. 61 54 6
9844100 1998
40
Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia. 61 54 6
9781036 1998
41
Hypophosphatasia: identification of five novel missense mutations (G507A, G705A, A748G, T1155C, G1320A) in the tissue-nonspecific alkaline phosphatase gene among Japanese patients. 61 54 6
9452105 1998
42
Aberrant properties of alkaline phosphatase in patient fibroblasts correlate with clinical expressivity in severe forms of hypophosphatasia. 61 54 6
8675582 1996
43
Novel missense and frameshift mutations in the tissue-nonspecific alkaline phosphatase gene in a Japanese patient with hypophosphatasia. 54 61 6
7833929 1994
44
A homoallelic Gly317-->Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian mennonites. 61 6 54
8406453 1993
45
Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia. 61 6 54
1409720 1992
46
Genotype-Phenotype Associations in 72 Adults with Suspected ALPL-Associated Hypophosphatasia. 6 61
33191482 2021
47
Large-scale in vitro functional testing and novel variant scoring via protein modeling provide insights into alkaline phosphatase activity in hypophosphatasia. 6 61
32160374 2020
48
Effect of Asfotase Alfa on Muscle Weakness in a Japanese Adult Patient of Hypophosphatasia with Low ALP Levels. 61 6
31787692 2020
49
Skeletal mineralization: mechanisms and diseases. 6 61
31905439 2019
50
Japanese nationwide survey of hypophosphatasia reveals prominent differences in genetic and dental findings between odonto and non-odonto types. 6 61
31600233 2019

Variations for Hypophosphatasia

ClinVar genetic disease variations for Hypophosphatasia:

6 (show top 50) (show all 266)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ALPL NM_000478.6(ALPL):c.1282C>T (p.Arg428Ter) SNV Pathogenic 929188 GRCh37: 1:21903107-21903107
GRCh38: 1:21576614-21576614
2 ALPL NM_000478.6(ALPL):c.738G>T (p.Arg246Ser) SNV Pathogenic 984475 GRCh37: 1:21894686-21894686
GRCh38: 1:21568193-21568193
3 ALPL NM_000478.6(ALPL):c.212G>C (p.Arg71Pro) SNV Pathogenic 13665 rs121918003 GRCh37: 1:21887620-21887620
GRCh38: 1:21561127-21561127
4 ALPL NM_000478.6(ALPL):c.620A>C (p.Gln207Pro) SNV Pathogenic 13666 rs121918004 GRCh37: 1:21890681-21890681
GRCh38: 1:21564188-21564188
5 ALPL NM_000478.6(ALPL):c.98C>T (p.Ala33Val) SNV Pathogenic 13667 rs121918005 GRCh37: 1:21887155-21887155
GRCh38: 1:21560662-21560662
6 ALPL NM_000478.6(ALPL):c.1306T>C (p.Tyr436His) SNV Pathogenic 13668 rs121918006 GRCh37: 1:21903131-21903131
GRCh38: 1:21576638-21576638
7 ALPL NM_000478.6(ALPL):c.892G>A (p.Glu298Lys) SNV Pathogenic 13669 rs121918017 GRCh37: 1:21900187-21900187
GRCh38: 1:21573694-21573694
8 ALPL NM_000478.6(ALPL):c.1559del (p.Leu520fs) Deletion Pathogenic 13674 rs387906525 GRCh37: 1:21904125-21904125
GRCh38: 1:21577632-21577632
9 ALPL NM_000478.6(ALPL):c.485G>T (p.Gly162Val) SNV Pathogenic 13676 rs121918012 GRCh37: 1:21890546-21890546
GRCh38: 1:21564053-21564053
10 ALPL NM_000478.6(ALPL):c.1250A>G (p.Asn417Ser) SNV Pathogenic 13679 rs121918014 GRCh37: 1:21903075-21903075
GRCh38: 1:21576582-21576582
11 ALPL NM_000478.6(ALPL):c.1366G>A (p.Gly456Arg) SNV Pathogenic 13681 rs121918016 GRCh37: 1:21903932-21903932
GRCh38: 1:21577439-21577439
12 ALPL NM_000478.6(ALPL):c.746G>T (p.Gly249Val) SNV Pathogenic 13682 rs121918018 GRCh37: 1:21894694-21894694
GRCh38: 1:21568201-21568201
13 ALPL NM_000478.6(ALPL):c.526G>A (p.Ala176Thr) SNV Pathogenic 13683 rs121918019 GRCh37: 1:21890587-21890587
GRCh38: 1:21564094-21564094
14 ALPL NM_000478.6(ALPL):c.814C>T (p.Arg272Cys) SNV Pathogenic 13684 rs121918020 GRCh37: 1:21896819-21896819
GRCh38: 1:21570326-21570326
15 ALPL NM_000478.6(ALPL):c.814C>T (p.Arg272Cys) SNV Pathogenic 13684 rs121918020 GRCh37: 1:21896819-21896819
GRCh38: 1:21570326-21570326
16 ALPL NM_000478.6(ALPL):c.1559del (p.Leu520fs) Deletion Pathogenic 13674 rs387906525 GRCh37: 1:21904125-21904125
GRCh38: 1:21577632-21577632
17 ALPL NM_000478.6(ALPL):c.997+2T>G SNV Pathogenic 371591 rs1057517391 GRCh37: 1:21900294-21900294
GRCh38: 1:21573801-21573801
18 ALPL NM_000478.6(ALPL):c.18del (p.Val7fs) Deletion Pathogenic 518424 rs1558543066 GRCh37: 1:21880592-21880592
GRCh38: 1:21554099-21554099
19 ALPL NM_000478.6(ALPL):c.1098_1100CTC[1] (p.Ser368del) Microsatellite Pathogenic 545020 rs1558557341 GRCh37: 1:21902325-21902327
GRCh38: 1:21575832-21575834
20 ALPL NM_000478.6(ALPL):c.400_401delinsCA (p.Thr134His) Indel Pathogenic 188877 rs786204530 GRCh37: 1:21889705-21889706
GRCh38: 1:21563212-21563213
21 ALPL NM_000478.6(ALPL):c.1471G>A (p.Gly491Arg) SNV Pathogenic 551446 rs1413274209 GRCh37: 1:21904037-21904037
GRCh38: 1:21577544-21577544
22 ALPL NM_000478.6(ALPL):c.529G>A (p.Ala177Thr) SNV Pathogenic 556961 rs199669988 GRCh37: 1:21890590-21890590
GRCh38: 1:21564097-21564097
23 ALPL NM_000478.6(ALPL):c.1363G>A (p.Gly455Ser) SNV Pathogenic 371400 rs149889416 GRCh37: 1:21903929-21903929
GRCh38: 1:21577436-21577436
24 ALPL NM_000478.6(ALPL):c.1250A>G (p.Asn417Ser) SNV Pathogenic 13679 rs121918014 GRCh37: 1:21903075-21903075
GRCh38: 1:21576582-21576582
25 ALPL NM_000478.6(ALPL):c.331G>A (p.Ala111Thr) SNV Pathogenic 829876 rs773257111 GRCh37: 1:21889636-21889636
GRCh38: 1:21563143-21563143
26 ALPL NM_000478.6(ALPL):c.571G>T (p.Glu191Ter) SNV Pathogenic 931472 GRCh37: 1:21890632-21890632
GRCh38: 1:21564139-21564139
27 ALPL NM_000478.6(ALPL):c.500C>T (p.Thr167Met) SNV Pathogenic 975901 GRCh37: 1:21890561-21890561
GRCh38: 1:21564068-21564068
28 ALPL NM_000478.6(ALPL):c.1250A>G (p.Asn417Ser) SNV Pathogenic 13679 rs121918014 GRCh37: 1:21903075-21903075
GRCh38: 1:21576582-21576582
29 ALPL NM_000478.6(ALPL):c.1190-2A>T SNV Pathogenic 976090 GRCh37: 1:21903013-21903013
GRCh38: 1:21576520-21576520
30 ALPL NM_000478.6(ALPL):c.46_49del (p.Asn16fs) Deletion Pathogenic 370095 rs1057516230 GRCh37: 1:21880617-21880620
GRCh38: 1:21554124-21554127
31 ALPL NM_000478.6(ALPL):c.98C>T (p.Ala33Val) SNV Pathogenic 13667 rs121918005 GRCh37: 1:21887155-21887155
GRCh38: 1:21560662-21560662
32 ALPL NM_000478.6(ALPL):c.526G>A (p.Ala176Thr) SNV Pathogenic 13683 rs121918019 GRCh37: 1:21890587-21890587
GRCh38: 1:21564094-21564094
33 ALPL NM_000478.6(ALPL):c.1017dup (p.His340fs) Duplication Pathogenic 554623 rs764908423 GRCh37: 1:21902242-21902243
GRCh38: 1:21575749-21575750
34 ALPL NM_000478.6(ALPL):c.1171C>T (p.Arg391Cys) SNV Pathogenic 550442 rs371243939 GRCh37: 1:21902399-21902399
GRCh38: 1:21575906-21575906
35 ALPL NM_000478.6(ALPL):c.1283G>C (p.Arg428Pro) SNV Pathogenic 992375 GRCh37: 1:21903108-21903108
GRCh38: 1:21576615-21576615
36 ALPL NM_000478.6(ALPL):c.1182dup (p.Ile395fs) Duplication Pathogenic 632629 rs754826836 GRCh37: 1:21902409-21902410
GRCh38: 1:21575916-21575917
37 ALPL NM_000478.6(ALPL):c.881A>C (p.Asp294Ala) SNV Pathogenic 13664 rs121918002 GRCh37: 1:21900176-21900176
GRCh38: 1:21573683-21573683
38 ALPL NM_000478.6(ALPL):c.881A>C (p.Asp294Ala) SNV Pathogenic 13664 rs121918002 GRCh37: 1:21900176-21900176
GRCh38: 1:21573683-21573683
39 ALPL NM_000478.6(ALPL):c.881A>C (p.Asp294Ala) SNV Pathogenic 13664 rs121918002 GRCh37: 1:21900176-21900176
GRCh38: 1:21573683-21573683
40 ALPL NM_000478.6(ALPL):c.571G>A (p.Glu191Lys) SNV Pathogenic 13670 rs121918007 GRCh37: 1:21890632-21890632
GRCh38: 1:21564139-21564139
41 ALPL NM_000478.6(ALPL):c.571G>A (p.Glu191Lys) SNV Pathogenic 13670 rs121918007 GRCh37: 1:21890632-21890632
GRCh38: 1:21564139-21564139
42 ALPL NM_000478.6(ALPL):c.571G>A (p.Glu191Lys) SNV Pathogenic 13670 rs121918007 GRCh37: 1:21890632-21890632
GRCh38: 1:21564139-21564139
43 ALPL NM_000478.6(ALPL):c.1133A>T (p.Asp378Val) SNV Pathogenic 13671 rs121918008 GRCh37: 1:21902361-21902361
GRCh38: 1:21575868-21575868
44 ALPL NM_000478.6(ALPL):c.1133A>T (p.Asp378Val) SNV Pathogenic 13671 rs121918008 GRCh37: 1:21902361-21902361
GRCh38: 1:21575868-21575868
45 ALPL NM_000478.6(ALPL):c.407G>A (p.Arg136His) SNV Pathogenic 13675 rs121918011 GRCh37: 1:21889712-21889712
GRCh38: 1:21563219-21563219
46 ALPL NM_000478.6(ALPL):c.346G>A (p.Ala116Thr) SNV Pathogenic 13677 rs121918013 GRCh37: 1:21889651-21889651
GRCh38: 1:21563158-21563158
47 ALPL NM_000478.6(ALPL):c.346G>A (p.Ala116Thr) SNV Pathogenic 13677 rs121918013 GRCh37: 1:21889651-21889651
GRCh38: 1:21563158-21563158
48 ALPL NM_000478.6(ALPL):c.407G>A (p.Arg136His) SNV Pathogenic 13675 rs121918011 GRCh37: 1:21889712-21889712
GRCh38: 1:21563219-21563219
49 ALPL NM_000478.6(ALPL):c.119C>T (p.Ala40Val) SNV Pathogenic 975919 GRCh37: 1:21887176-21887176
GRCh38: 1:21560683-21560683
50 ALPL NM_000478.6(ALPL):c.1133A>T (p.Asp378Val) SNV Pathogenic 13671 rs121918008 GRCh37: 1:21902361-21902361
GRCh38: 1:21575868-21575868

Expression for Hypophosphatasia

Search GEO for disease gene expression data for Hypophosphatasia.

Pathways for Hypophosphatasia

Pathways related to Hypophosphatasia according to KEGG:

36
# Name Kegg Source Accession
1 Folate biosynthesis hsa00790

Pathways related to Hypophosphatasia according to GeneCards Suite gene sharing:

(show all 13)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.11 ENPP1 ALPP ALPL ALPI ALPG
2
Show member pathways
12.05 PNPO ALPP ALPL ALPI ALPG
3 11.82 RUNX2 PTH PLCB4 BGLAP
4
Show member pathways
11.77 PIGT ALPL ALPI ALPG
5 11.7 SPP1 RUNX2 PTH BGLAP ALPP
6 11.38 SPP1 RUNX2 PLCG1 BGLAP
7 11.37 SPP1 RUNX2 PTH ENPP1 ALPL
8 11.32 SPP1 RUNX2 PTH BGLAP
9
Show member pathways
11.02 ALPP ALPL ALPI ALPG
10 10.67 PTH BGLAP
11 10.61 SPP1 RUNX2 PTH PLCB4 BGLAP
12
Show member pathways
10.55 PNPO ALPP
13 10.46 ALPP ALPL ALPI ALPG

GO Terms for Hypophosphatasia

Cellular components related to Hypophosphatasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.85 SPP1 SLPI PTH ENPP1 DSPP CCL27
2 anchored component of membrane GO:0031225 9.26 ALPP ALPL ALPI ALPG
3 extracellular membrane-bounded organelle GO:0065010 8.62 PHOSPHO1 ALPL

Biological processes related to Hypophosphatasia according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 dephosphorylation GO:0016311 9.72 PHOSPHO1 ALPP ALPL ALPI ALPG
2 ossification GO:0001503 9.71 SPP1 RUNX2 DSPP BGLAP
3 skeletal system development GO:0001501 9.7 RUNX2 PTH PHEX DSPP BGLAP ANKH
4 osteoblast differentiation GO:0001649 9.67 SPP1 RUNX2 BGLAP ALPL
5 endochondral ossification GO:0001958 9.61 RUNX2 PHOSPHO1 ALPL
6 regulation of bone mineralization GO:0030500 9.56 PHOSPHO1 ENPP1 BGLAP ANKH
7 osteoblast development GO:0002076 9.49 RUNX2 BGLAP
8 cellular response to vitamin D GO:0071305 9.48 PHEX BGLAP
9 inorganic diphosphate transport GO:0030505 9.46 ENPP1 ANKH
10 response to vitamin D GO:0033280 9.35 SPP1 PTH PHEX BGLAP ALPL
11 biomineral tissue development GO:0031214 9.1 SPP1 PHEX ENPP1 DSPP BGLAP ALPL

Molecular functions related to Hypophosphatasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.81 PLCG1 PLCB4 PHOSPHO1 PHEX ENPP1 ALPP
2 catalytic activity GO:0003824 9.72 ENPP1 ALPP ALPL ALPI ALPG
3 phospholipase C activity GO:0004629 9.37 PLCG1 PLCB4
4 phosphatase activity GO:0016791 9.35 PHOSPHO1 ALPP ALPL ALPI ALPG
5 pyrophosphatase activity GO:0016462 9.26 PHOSPHO1 ALPL
6 alkaline phosphatase activity GO:0004035 8.92 ALPP ALPL ALPI ALPG

Sources for Hypophosphatasia

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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