GKD
MCID: GLY014
MIFTS: 48

Glycerol Kinase Deficiency (GKD)

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

Aliases & Classifications for Glycerol Kinase Deficiency

MalaCards integrated aliases for Glycerol Kinase Deficiency:

Name: Glycerol Kinase Deficiency 57 12 20 58 73 36 13 54 15
Hyperglycerolemia 57 74 20 58 73
Deficiency of Glycerol Kinase 29 6 71
Gk1 Deficiency 57 20 73
Gk Deficiency 57 20 73
Gkd 57 20 73
Glycerol Kinase Deficiency, Juvenile Form 58
Glycerol Kinase Deficiency, Adult Form 58
Isolated Glycerol Kinase Deficiency 58
Deficiency, Glycerol Kinase 39

Characteristics:

Orphanet epidemiological data:

58
isolated glycerol kinase deficiency
Inheritance: X-linked recessive; Age of onset: All ages;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
x-linked recessive

Miscellaneous:
variable clinical phenotype
infantile form (gene deletion 'complex' with glycerol kinase deficiency and/or duchenne muscular dystrophy and/or congenital adrenal hypoplasia)
juvenile and adult forms are isolated glycerol kinase deficiency
adult form is asymptomatic


HPO:

31
glycerol kinase deficiency:
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism


Summaries for Glycerol Kinase Deficiency

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 408DefinitionIsolated glycerol kinase deficiency (GKD) is a very rare X-linked disorder of glycerol metabolism characterized biochemically by elevated plasma and urine glycerol levels, and clinically by variable neurometabolic manifestations, depending on the age of onset, and varying from a life-threatening childhood metabolic crisis to an asymptomatic adult form (infantile GKD, juvenile GKD, and adult GKD (see these terms)).Visit the Orphanet disease page for more resources.

MalaCards based summary : Glycerol Kinase Deficiency, also known as hyperglycerolemia, is related to chromosome xp21 deletion syndrome and adrenal hypoplasia, congenital, and has symptoms including seizures An important gene associated with Glycerol Kinase Deficiency is GK (Glycerol Kinase), and among its related pathways/superpathways are Glycerolipid metabolism and PPAR signaling pathway. Affiliated tissues include eye, liver and skeletal muscle, and related phenotypes are intellectual disability and neurological speech impairment

Disease Ontology : 12 An inherited metabolic disorder characterized by wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype and that has material basis in mutation in the GK gene on chromosome Xp21.

OMIM® : 57 Francke et al. (1987) noted that there are 3 clinically distinct forms of glycerol kinase deficiency: infantile, juvenile, and adult. The infantile form is associated with severe developmental delay, and those with the adult form have no symptoms and are often detected fortuitously. The infantile form of GK deficiency, or the 'GK complex,' results from the Xp21 contiguous gene deletion syndrome (300679) with congenital adrenal hypoplasia (300200) and/or Duchenne muscular dystrophy (DMD; 310200), whereas the juvenile and adult forms have isolated GK deficiency (Walker et al., 1996). (307030) (Updated 05-Mar-2021)

KEGG : 36 Glycerol kinase deficiency is an X-linked recessive disorder. There are two types, an isolated form and a complex form (chromosome Xp21 deletion syndrome). Isolated glycerol kinase deficiency results from mutations in GK gene. It has an inconstant phenotype, ranging from asymptomatic hyperglycerolemia to a severe metabolic disorder with growth and psychomotor retardation.

UniProtKB/Swiss-Prot : 73 Glycerol kinase deficiency: A metabolic disorder manifesting as 3 clinically distinct forms: infantile, juvenile, and adult. The infantile form is the most severe and is associated with severe developmental delay and adrenal insufficiency. Patients with the adult form have no symptoms and are often detected fortuitously. GKD results in hyperglycerolemia, a condition characterized by the accumulation of glycerol in the blood and urine.

Wikipedia : 74 Hyperglycerolemia, also known as Glycerol kinase deficiency (GKD), is a genetic disorder where the... more...

Related Diseases for Glycerol Kinase Deficiency

Diseases related to Glycerol Kinase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 66)
# Related Disease Score Top Affiliating Genes
1 chromosome xp21 deletion syndrome 32.9 NR0B1 IL1RAPL1 DMD
2 adrenal hypoplasia, congenital 31.6 NR5A1 NR0B1 IL1RAPL1 GK2 GK DMD
3 muscular dystrophy, duchenne type 31.1 NR0B1 GK2 GK DMD
4 hypoadrenocorticism, familial 30.7 NR5A1 NR0B1 IL1RAPL1 GK
5 nr0b1-related adrenal hypoplasia congenita 30.0 NR0B1 IL1RAPL1 GK DMD
6 aland island eye disease 30.0 NYX GK DMD
7 muscular dystrophy 10.7
8 myopathy 10.4
9 hypoglycemia 10.4
10 hypertriglyceridemia, familial 10.3
11 nonsyndromic disorders of testicular development 10.2 NR5A1 NR0B1
12 46,xy partial gonadal dysgenesis 10.2 NR5A1 NR0B1
13 nivelon-nivelon-mabille syndrome 10.2 NR5A1 NR0B1
14 steroid inherited metabolic disorder 10.2 NR5A1 NR0B1
15 corticosterone methyloxidase type i deficiency 10.2 NR5A1 NR0B1
16 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 10.2 NR5A1 NR0B1 GK
17 46,xx sex reversal 10.1 NR5A1 NR0B1
18 adrenal cortical hypofunction 10.1 NR5A1 NR0B1
19 lipoid congenital adrenal hyperplasia 10.1
20 muscular dystrophy, becker type 10.1
21 alacrima, achalasia, and mental retardation syndrome 10.1
22 metabolic acidosis 10.1
23 dystrophinopathies 10.1
24 hypotonia 10.1
25 spasticity 10.1
26 progressive muscular dystrophy 10.1
27 persistent mullerian duct syndrome 10.0 NR5A1 NR0B1
28 gastroenteritis 10.0
29 glycogen storage disease ia 10.0 SLC37A4 SLC37A3 SLC37A1
30 type 2 diabetes mellitus 9.9
31 hypertelorism 9.9
32 fanconi anemia, complementation group a 9.9
33 batten-turner congenital myopathy 9.9
34 ocular motor apraxia 9.9
35 retinitis pigmentosa 9.9
36 branchiootic syndrome 1 9.9
37 dermatitis, atopic 9.9
38 abdominal obesity-metabolic syndrome 1 9.9
39 premature ovarian failure 7 9.9
40 deficiency anemia 9.9
41 hemophagocytic lymphohistiocytosis 9.9
42 ocular albinism 9.9
43 hypogonadotropic hypogonadism 9.9
44 neuroretinitis 9.9
45 monocular esotropia 9.9
46 hydrocephalus 9.9
47 allergic disease 9.9
48 cholestasis 9.9
49 hereditary angioedema 9.9
50 angioedema 9.9

Graphical network of the top 20 diseases related to Glycerol Kinase Deficiency:



Diseases related to Glycerol Kinase Deficiency

Symptoms & Phenotypes for Glycerol Kinase Deficiency

Human phenotypes related to Glycerol Kinase Deficiency:

58 31 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 neurological speech impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0002167
3 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
4 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
5 myopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003198
6 elevated serum creatine kinase 58 31 hallmark (90%) Very frequent (99-80%) HP:0003236
7 emg abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0003457
8 reduced tendon reflexes 58 31 hallmark (90%) Very frequent (99-80%) HP:0001315
9 metabolic acidosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001942
10 adrenocortical hypoplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008182
11 hypotonia 31 hallmark (90%) HP:0001252
12 eeg abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0002353
13 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
14 hyperlordosis 58 31 frequent (33%) Frequent (79-30%) HP:0003307
15 cryptorchidism 58 31 occasional (7.5%) Frequent (79-30%) HP:0000028
16 osteoporosis 58 31 frequent (33%) Frequent (79-30%) HP:0000939
17 seizure 31 frequent (33%) HP:0001250
18 abnormal facial shape 31 occasional (7.5%) HP:0001999
19 seizures 58 Frequent (79-30%)
20 frontal bossing 31 HP:0002007
21 muscular hypotonia 58 Very frequent (99-80%)
22 hypertelorism 31 HP:0000316
23 hypoglycemia 31 HP:0001943
24 hypertriglyceridemia 31 HP:0002155
25 strabismus 31 HP:0000486
26 growth delay 31 HP:0001510
27 low-set ears 31 HP:0000369
28 downturned corners of mouth 31 HP:0002714
29 lethargy 31 HP:0001254
30 muscular dystrophy 31 HP:0003560
31 psychomotor retardation 31 HP:0025356
32 coma 31 HP:0001259
33 small for gestational age 31 HP:0001518
34 loss of consciousness 31 HP:0007185
35 adrenal insufficiency 31 HP:0000846
36 ketoacidosis 31 HP:0001993
37 pathologic fracture 31 HP:0002756
38 episodic vomiting 31 HP:0002572
39 increased urinary glycerol 31 HP:0040301

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
seizures
psychomotor retardation
mental retardation may occur

Head And Neck Eyes:
hypertelorism
strabismus
rounded palpebral fissures

Laboratory Abnormalities:
hypoglycemia
increased urinary glycerol
increased serum glycerol
decreased glycerol kinase activity
pseudohypertriglyceridemia in adult form

Head And Neck Ears:
low-set ears
wide, flattened earlobes

Growth Other:
small for gestational age

Genitourinary Internal Genitalia Male:
cryptorchidism may occur

Endocrine Features:
adrenal insufficiency, congenital in 'complex' form

Head And Neck Face:
frontal bossing
mild facial dysmorphism may occur
'hourglass' midface

Growth Height:
short stature

Skeletal:
osteoporosis

Metabolic Features:
metabolic acidosis
ketoacidosis
lethargy or loss of consciousness during illness or fasting

Head And Neck Mouth:
downturned mouth

Muscle Soft Tissue:
duchenne muscular dystrophy (dmd, ) in 'complex' form

Clinical features from OMIM®:

307030 (Updated 05-Mar-2021)

UMLS symptoms related to Glycerol Kinase Deficiency:


seizures

Drugs & Therapeutics for Glycerol Kinase Deficiency

Search Clinical Trials , NIH Clinical Center for Glycerol Kinase Deficiency

Genetic Tests for Glycerol Kinase Deficiency

Genetic tests related to Glycerol Kinase Deficiency:

# Genetic test Affiliating Genes
1 Deficiency of Glycerol Kinase 29 GK

Anatomical Context for Glycerol Kinase Deficiency

MalaCards organs/tissues related to Glycerol Kinase Deficiency:

40
Eye, Liver, Skeletal Muscle, Thyroid, Skin, Pituitary

Publications for Glycerol Kinase Deficiency

Articles related to Glycerol Kinase Deficiency:

(show top 50) (show all 165)
# Title Authors PMID Year
1
Clinical heterogeneity and novel mutations in the glycerol kinase gene in three families with isolated glycerol kinase deficiency. 6 57 61 54
9719371 1998
2
Mutations and phenotype in isolated glycerol kinase deficiency. 54 6 57 61
8651297 1996
3
Glycerol as a correlate of impaired glucose tolerance: dissection of a complex system by use of a simple genetic trait. 61 57 6
10736265 2000
4
Isolated and contiguous glycerol kinase gene disorders: a review. 61 54 57
11032329 2000
5
AluY insertion (IVS4-52ins316alu) in the glycerol kinase gene from an individual with benign glycerol kinase deficiency. 61 54 6
10737976 2000
6
Glycerol kinase deficiency alters expression of genes involved in lipid metabolism, carbohydrate metabolism, and insulin signaling. 57 61
17406644 2007
7
Congenital adrenal hypoplasia, myopathy, and glycerol kinase deficiency: molecular genetic evidence for deletions. 61 57
2883886 1987
8
Adrenal dysfunction in glycerol kinase deficiency. 57 61
2988520 1985
9
A juvenile form of glycerol kinase deficiency with episodic vomiting, acidemia, and stupor. 57 61
6325658 1984
10
Human glycerol kinase deficiency: an inborn error of compartmental metabolism. 61 57
6316939 1983
11
Concordance of X-linked glycerol kinase deficiency with X-linked congenital adrenal hypoplasia. 61 57
6125810 1982
12
'Pseudohypertriglyceridemia' caused by hyperglycerolemia due to congenital enzyme deficiency. 57 61
6288290 1982
13
Glycerol kinase deficiency with neuromuscular, skeletal, and adrenal abnormalities. 61 57
6249182 1980
14
Familial hyperglycerolemia. 57 61
618910 1978
15
Human glycerol kinase deficiency with hyperglycerolemia and glyceroluria. 57 61
200232 1977
16
Proposed assignment of loci for X-linked adrenal hypoplasia and glycerol kinase genes. 57
2856983 1985
17
Deficiency of glycerol kinase (EC 2.7.1.30). 57
6299616 1983
18
[Contiguous gene deletion syndrome in Xp21: an unusual form of presentation]. 61 54
19859888 2009
19
Weighted gene co-expression network analysis identifies biomarkers in glycerol kinase deficient mice. 54 61
19546021 2009
20
Pseudo-hypertriglyceridaemia: a measurement artefact due to glycerol kinase deficiency. 54 61
19017842 2008
21
Acute liver failure in a child with Epstein-Barr virus infection and undiagnosed glycerol kinase deficiency, mimicking hemophagocytic lymphohistiocytosis. 61 54
18607276 2008
22
[Complex glycerol kinase deficiency in three children]. 54 61
17937854 2007
23
[Contiguous gene deletion syndrome in Xp21: the association between glycerol kinase deficiency, congenital suprarenal hypoplasia and Duchenne's muscular dystrophy]. 54 61
17523119 2007
24
Two cases of isolated glycerol kinase deficiency with heterogeneous neurological symptoms. 54 61
17489818 2007
25
A multiplex assay for the detection and mapping of complex glycerol kinase deficiency. 61 54
16887896 2006
26
Asymptomatic isolated human glycerol kinase deficiency associated with splice-site mutations and nonsense-mediated decay of mutant RNA. 61 54
16549535 2006
27
Targeted disruption of glycerol kinase gene in mice: expression analysis in liver shows alterations in network partners related to glycerol kinase activity. 61 54
16368706 2006
28
Comparison of triglyceride concentration with lipemic index in disorders of triglyceride and glycerol metabolism. 54 61
16475911 2006
29
Gene therapy for murine glycerol kinase deficiency: importance of murine ortholog. 61 54
16105550 2005
30
Novel mutation (Gly280Ala) in the ATP-binding domain of glycerol kinase causes severe hyperglycerolemia. 61 54
16025401 2005
31
Glycerol kinase deficiency presenting with hypodipsia, osmotic diuresis and severe hypernatraemia. 54 61
16435217 2005
32
Complex glycerol kinase deficiency: an X-linked disorder associated with adrenal hypoplasia congenita. 61 54
15684452 2005
33
Identification of novel mutations of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita. 54 61
15860922 2005
34
IL1RAPL1 is associated with mental retardation in patients with complex glycerol kinase deficiency who have deletions extending telomeric of DAX1. 54 61
15300857 2004
35
Glycerol kinase deficiency: follow-up during 20 years, genetics, biochemistry and prognosis. 61 54
15303806 2004
36
Glycerol kinase deficiency: residual activity explained by reduced transcription and enzyme conformation. 61 54
15026783 2004
37
Complex glycerol kinase deficiency leads to psychomotor and body-growth failure. 54 61
15009558 2004
38
Clinical heterogeneity and molecular findings in five Polish patients with glycerol kinase deficiency: investigation of two splice site mutations with computerized splice junction analysis and Xp21 gene-specific mRNA analysis. 61 54
12855219 2003
39
The Colorado mental retardation and developmental disabilities research center. 54 61
12175865 2002
40
Isolated glycerol kinase deficiency and Fanconi anemia. 61 54
11241478 2001
41
[Glycerol kinase deficiency with dystrophinopathy]. 61 54
11555931 2001
42
Cloning and characterization of a putative human glycerol 3-phosphate permease gene (SLC37A1 or G3PP) on 21q22.3: mutation analysis in two candidate phenotypes, DFNB10 and a glycerol kinase deficiency. 61 54
11112347 2000
43
Hyperketonaemia in glycerol kinase deficiency. 61 54
11117440 2000
44
Rapid, simplified and sensitive method for screening fructose-1,6-diphosphatase deficiency by analyzing urinary metabolites in urease/direct preparations and gas chromatography-mass spectrometry in the selected-ion monitoring mode. 54 61
11048742 2000
45
Five cases of isolated glycerol kinase deficiency, including two families: failure to find genotype:phenotype correlation. 61 54
10851254 2000
46
Duchenne muscular dystrophy and glycerol kinase deficiency: a rare contiguous gene syndrome. 61 54
19078586 2000
47
Two novel members of the interleukin-1 receptor gene family, one deleted in Xp22.1-Xp21.3 mental retardation. 61 54
10757639 2000
48
IMAGe, a new clinical association of intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies. 61 54
10599684 1999
49
Congenital adrenal hypoplasia: clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the DAX-1 gene. 61 54
9709929 1998
50
[Syndrome of contiguous gene deletions in Xp-21 (deficiency of the glycerol-kinase complex). The association of Duchenne muscular dystrophy, glycerol kinase deficiency and congenital suprarenal hypoplasia]. 61 54
9575126 1997

Variations for Glycerol Kinase Deficiency

ClinVar genetic disease variations for Glycerol Kinase Deficiency:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GK NM_000167.5(GK):c.553-1G>C SNV Pathogenic 10941 rs587776740 X:30714158-30714158 X:30696041-30696041
2 GK NC_000023.11:g.(30720096_30720620)_(30720742_30720851)del Deletion Pathogenic 10942 X:30738213-30738968 X:30720096-30720851
3 GK NM_000167.5(GK):c.1319A>T (p.Asp440Val) SNV Pathogenic 10943 rs132630328 X:30738838-30738838 X:30720721-30720721
4 GK-AS1 NC_000023.11:g.(30700906_30707555)_(30728743_?)del Deletion Pathogenic 10944 X:30700906-30728743
5 GK NM_000167.5(GK):c.1237C>T (p.Arg413Ter) SNV Pathogenic 10945 rs132630329 X:30738756-30738756 X:30720639-30720639
6 GK NM_000167.5(GK):c.1507T>C (p.Trp503Arg) SNV Pathogenic 10946 rs132630330 X:30742241-30742241 X:30724124-30724124
7 GK NM_001128127.2(GK):c.42765-52ins316 Insertion Pathogenic 10947
8 GK-AS1 NM_000167.5(GK):c.862A>G (p.Asn288Asp) SNV Pathogenic 10948 rs132630331 X:30725701-30725701 X:30707584-30707584

UniProtKB/Swiss-Prot genetic disease variations for Glycerol Kinase Deficiency:

73
# Symbol AA change Variation ID SNP ID
1 GK p.Asp446Val VAR_001377 rs132630328
2 GK p.Trp509Arg VAR_010138 rs132630330
3 GK p.Asn294Asp VAR_015433 rs132630331

Expression for Glycerol Kinase Deficiency

Search GEO for disease gene expression data for Glycerol Kinase Deficiency.

Pathways for Glycerol Kinase Deficiency

Pathways related to Glycerol Kinase Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Glycerolipid metabolism hsa00561
2 PPAR signaling pathway hsa03320

Pathways related to Glycerol Kinase Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.98 GPD1 GK2 GK
2
Show member pathways
10.52 GPD1 GK
3 9.23 GK2 GK

GO Terms for Glycerol Kinase Deficiency

Cellular components related to Glycerol Kinase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of endoplasmic reticulum membrane GO:0030176 8.8 SLC37A4 SLC37A3 SLC37A1

Biological processes related to Glycerol Kinase Deficiency according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 carbohydrate metabolic process GO:0005975 9.65 GPD1 GK2 GK FGGY DMD
2 carbohydrate transport GO:0008643 9.58 SLC37A4 SLC37A3 SLC37A1
3 regulation of presynapse assembly GO:1905606 9.52 IL1RAPL2 IL1RAPL1
4 adrenal gland development GO:0030325 9.51 NR5A1 NR0B1
5 triglyceride metabolic process GO:0006641 9.5 SLC37A4 GK2 GK
6 glycerol metabolic process GO:0006071 9.49 GK2 GK
7 male sex determination GO:0030238 9.48 NR5A1 NR0B1
8 sex determination GO:0007530 9.46 NR5A1 NR0B1
9 glycerol catabolic process GO:0019563 9.43 GK2 GK
10 glycerol-3-phosphate biosynthetic process GO:0046167 9.37 GK2 GK
11 phosphate ion transmembrane transport GO:0035435 9.33 SLC37A4 SLC37A3 SLC37A1
12 glycerol-3-phosphate metabolic process GO:0006072 9.13 GPD1 GK2 GK
13 glucose-6-phosphate transport GO:0015760 8.8 SLC37A4 SLC37A3 SLC37A1

Molecular functions related to Glycerol Kinase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 NAD+ nucleotidase, cyclic ADP-ribose generating GO:0061809 9.32 IL1RAPL2 IL1RAPL1
2 NAD(P)+ nucleosidase activity GO:0050135 9.26 IL1RAPL2 IL1RAPL1
3 glycerol kinase activity GO:0004370 9.16 GK2 GK
4 phosphotransferase activity, alcohol group as acceptor GO:0016773 9.13 GK2 GK FGGY
5 glucose 6-phosphate:inorganic phosphate antiporter activity GO:0061513 8.8 SLC37A4 SLC37A3 SLC37A1

Sources for Glycerol Kinase Deficiency

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