GSD9A1
MCID: GLY099
MIFTS: 32

Glycogen Storage Disease Ixa1 (GSD9A1)

Categories: Genetic diseases, Liver diseases, Metabolic diseases

Aliases & Classifications for Glycogen Storage Disease Ixa1

MalaCards integrated aliases for Glycogen Storage Disease Ixa1:

Name: Glycogen Storage Disease Ixa1 56 73 71
Glycogen Storage Disease, Type Ixa1 56 13
Glycogen Storage Disease, Type Ixa2 56 71
Glycogen Storage Disease Type Ixa1 29 6
Glycogen Storage Disease Ixa2 73 6
Gsd9a1 56 73
Liver Glycogenosis, X-Linked, Type I; Xlg1 56
Glycogen Storage Disease Viii, Formerly 56
Hepatic Phosphorylase Kinase Deficiency 73
Liver Glycogenosis, X-Linked, Type I 56
Storage Disease, Glycogen, Type Ixa1 39
X-Linked Liver Glycogenosis Type Ii 73
Gsd Viii, Formerly; Gsd8, Formerly 56
Glycogen Storage Disease Type Viii 71
X-Linked Liver Glycogenosis Type I 73
Glycogen Storage Disease, Type Ix 71
Glycogen Storage Disease Viii 73
Glycogen Storage Disease Ixa 73
Glycogen Storage Disease Via 73
Glycogen Storage Disease 9a 73
X-Linked Liver Glycogenosis 73
Gsd Viii, Formerly 56
Gsd8, Formerly 56
Gsd-Viii 73
Gsd-Ixa 73
Gsd-Via 73
Gsd9a2 73
Gsd9a 73
Xlg1 56
Xlg 73

Characteristics:

OMIM:

56
Inheritance:
x-linked recessive

Miscellaneous:
clinical and biochemical abnormalities disappear with age


HPO:

31
glycogen storage disease ixa1:
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Glycogen Storage Disease Ixa1

OMIM : 56 Glycogen storage disease type IX is a metabolic disorder resulting from a deficiency of hepatic phosphorylase kinase, a hexadecameric enzyme comprising 4 copies each of 4 unique subunits encoded by 4 different genes: alpha (PHKA2), beta (PHKB; 172490), gamma (PHKG2; 172471), and delta (CALM1; 114180). Mutations within the PHKA2, PHKB, and PHKG2 genes result in GSD9A, GSD9B (261750), and GSD9C (613027), respectively. GSD IXa is an X-linked recessive disorder, whereas the others are autosomal recessive. GSD IXa has been further divided into types IXa1 (GSD9A1), with no PHK activity in liver or erythrocytes, and IXa2 (GSD9A2), with no PHK in liver, but normal activity in erythrocytes. The clinical presentation of both subtypes is the same, and both are caused by mutations in the PHKA2 gene. However, mutations that result in IXa2 are either missense or small in-frame deletions or insertions enabling residual enzyme expression in erythrocytes (Keating et al., 1985; Hendrickx et al., 1994; Beauchamp et al., 2007). See also X-linked muscle PHK deficiency (GSD9D; 300559), caused by mutation in the gene encoding the muscle-specific alpha PHK subunit (PHKA1; 311870). (306000)

MalaCards based summary : Glycogen Storage Disease Ixa1, also known as glycogen storage disease, type ixa1, is related to glycogen storage disease ixa and glycogen storage disease viii. An important gene associated with Glycogen Storage Disease Ixa1 is PHKA2 (Phosphorylase Kinase Regulatory Subunit Alpha 2). Affiliated tissues include liver, and related phenotypes are hypoglycemia and hepatomegaly

UniProtKB/Swiss-Prot : 73 Glycogen storage disease 9A: A metabolic disorder resulting in a mild liver glycogenosis with clinical symptoms that include hepatomegaly, growth retardation, muscle weakness, elevation of glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase, hypercholesterolemia, hypertriglyceridemia, and fasting hyperketosis. Two subtypes are known: type 1 or classic type with no phosphorylase kinase activity in liver or erythrocytes, and type 2 or variant type with no phosphorylase kinase activity in liver, but normal activity in erythrocytes. Unlike other glycogenosis diseases, glycogen storage disease type 9A is generally a benign condition. Patients improve with age and are often asymptomatic as adults. Accurate diagnosis is therefore also of prognostic interest.

Related Diseases for Glycogen Storage Disease Ixa1

Diseases related to Glycogen Storage Disease Ixa1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 glycogen storage disease ixa 12.8
2 glycogen storage disease viii 12.7
3 glycogen storage disease due to liver phosphorylase kinase deficiency 11.3
4 hypoglycemia 10.2
5 glycogen storage disease 10.2
6 phosphorylase kinase deficiency 10.2
7 renal tubular acidosis, proximal 10.1
8 glycogen storage disease ia 10.1
9 renal tubular acidosis 10.1
10 sensory peripheral neuropathy 10.1
11 insulin-like growth factor i 10.0
12 metabolic acidosis 10.0

Graphical network of the top 20 diseases related to Glycogen Storage Disease Ixa1:



Diseases related to Glycogen Storage Disease Ixa1

Symptoms & Phenotypes for Glycogen Storage Disease Ixa1

Human phenotypes related to Glycogen Storage Disease Ixa1:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 hypoglycemia 31 frequent (33%) HP:0001943
2 hepatomegaly 31 HP:0002240
3 hypertriglyceridemia 31 HP:0002155
4 growth delay 31 HP:0001510
5 elevated hepatic transaminase 31 HP:0002910
6 motor delay 31 HP:0001270
7 hypercholesterolemia 31 HP:0003124
8 ketosis 31 HP:0001946

Symptoms via clinical synopsis from OMIM:

56
Abdomen Liver:
hepatomegaly
liver histology reveals glycogen-distended hepatocytes

Laboratory Abnormalities:
variable hypoglycemia
liver phosphorylase kinase (phk) deficiency
phosphorylase kinase normal in muscle
mild elevation of transaminases
mild elevation of cholesterol
more
Growth Height:
growth retardation
normal final adult height

Neurologic Central Nervous System:
motor developmental delay, mild

Clinical features from OMIM:

306000

Drugs & Therapeutics for Glycogen Storage Disease Ixa1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Biomarker for Glycogen Storage Diseases - AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL Active, not recruiting NCT02385162

Search NIH Clinical Center for Glycogen Storage Disease Ixa1

Genetic Tests for Glycogen Storage Disease Ixa1

Genetic tests related to Glycogen Storage Disease Ixa1:

# Genetic test Affiliating Genes
1 Glycogen Storage Disease Type Ixa1 29 PHKA2

Anatomical Context for Glycogen Storage Disease Ixa1

MalaCards organs/tissues related to Glycogen Storage Disease Ixa1:

40
Liver

Publications for Glycogen Storage Disease Ixa1

Articles related to Glycogen Storage Disease Ixa1:

(show all 30)
# Title Authors PMID Year
1
X-linked liver glycogenosis type II (XLG II) is caused by mutations in PHKA2, the gene encoding the liver alpha subunit of phosphorylase kinase. 61 56 6
8733133 1996
2
Glycogen storage disease type IX: High variability in clinical phenotype. 56 6
17689125 2007
3
Clinical, biochemical and molecular findings in a patient with X-linked liver glycogenosis followed for 40 years. 56 6
9835437 1998
4
Variability of biochemical and clinical phenotype in X-linked liver glycogenosis with mutations in the phosphorylase kinase PHKA2 gene. 6 56
9600238 1998
5
Mutation hotspots in the PHKA2 gene in X-linked liver glycogenosis due to phosphorylase kinase deficiency with atypical activity in blood cells (XLG2). 6 56
8733134 1996
6
X-linked liver phosphorylase kinase deficiency is associated with mutations in the human liver phosphorylase kinase alpha subunit. 56 6
7847371 1995
7
Mutations in the phosphorylase kinase gene PHKA2 are responsible for X-linked liver glycogen storage disease. 6 56
7711737 1995
8
The natural history of liver glycogenosis due to phosphorylase kinase deficiency: a longitudinal study of 41 patients. 56 6
2303074 1990
9
X-chromosomal inheritance of liver glycogenosis with phosphorylase kinase deficiency. 56 6
5306139 1969
10
The natural history of glycogen storage disease types VI and IX: Long-term outcome from the largest metabolic center in Canada. 56
25266922 2014
11
Phosphorylase Kinase Deficiency 6
21634085 2011
12
Complete genomic structure and mutational spectrum of PHKA2 in patients with x-linked liver glycogenosis type I and II. 56
10330341 1999
13
Localization of a new type of X-linked liver glycogenosis to the chromosomal region Xp22 containing the liver alpha-subunit of phosphorylase kinase (PHKA2). 56
7959740 1994
14
Phosphorylase kinase deficiency in I-strain mice is associated with a frameshift mutation in the alpha subunit muscle isoform. 56
8298647 1993
15
X-linked liver glycogenosis: localization and isolation of a candidate gene. 56
8518797 1993
16
Mapping of the gene for X-linked liver glycogenosis due to phosphorylase kinase deficiency to human chromosome region Xp22. 56
1674721 1991
17
X-linked glycogen storage disease. A cause of hypotonia, hyperuricemia, and growth retardation. 56
3859203 1985
18
Lymphocyte phosphorylase kinase activities in the sex-linked form of liver phosphorylase kinase deficiency. 56
3987709 1985
19
X-linked dominant inheritance of partial phosphorylase kinase deficiency in mice. 56
7447922 1980
20
Dextrothyroxine treatment of phosphorylase-kinase deficiency glycogenosis in four boys. 56
280544 1978
21
Glycogen storage disease, types I to X: criteria for morphologic diagnosis. 56
4525190 1974
22
Glycogen-storage disease associated with phosphorylase kinase deficiency: evidence for X inactivation. 56
4524311 1974
23
Glycogen storage disease type IX: benign glycogenosis of liver and hepatic phosphorylase kinase deficiency. 56
4518931 1973
24
Liver glycogenosis and phosphorylase kinase deficiency. 56
5270453 1970
25
Glycogen-storage disease Type VIa: low phosphorylase kinase activity caused by a low enzyme-substrate affinity. 56
5266383 1970
26
Phosphorylase kinase deficiency. 56
5444101 1970
27
Deficient activity of dephosphophosphorylase kinase and accumulation of glycogen in the liver. 56
5774108 1969
28
Hepatic phosphorylase defect. Studies on peripheral blood. 56
5904467 1966
29
Low leukocyte phosphorylase in hepatic phosphorylase-deficient glycogen storage disease. 56
14007166 1961
30
[Enzymatic studies of hepatic fragments; application to the classification of glycogenoses]. 56
13646331 1959

Variations for Glycogen Storage Disease Ixa1

ClinVar genetic disease variations for Glycogen Storage Disease Ixa1:

6 (show top 50) (show all 92) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PHKA2 NM_000292.3(PHKA2):c.1794-8_1812deldeletion Pathogenic 526623 rs1556000892 X:18938301-18938327 X:18920183-18920209
2 PHKA2 NM_000292.3(PHKA2):c.1054C>T (p.Arg352Ter)SNV Pathogenic 526624 rs1556007472 X:18954256-18954256 X:18936138-18936138
3 PHKA2 NM_000292.3(PHKA2):c.2465del (p.Leu822fs)deletion Pathogenic 578458 rs1569298646 X:18926070-18926070 X:18907952-18907952
4 PHKA2 NC_000023.11:g.(?_18920012)_(18920221_?)deldeletion Pathogenic 583617 X:18938130-18938339 X:18920012-18920221
5 PHKA2 NM_000292.3(PHKA2):c.2772_2782del (p.Met924fs)deletion Pathogenic 568551 rs1569297379 X:18924637-18924647 X:18906519-18906529
6 PHKA2 NM_000292.3(PHKA2):c.2209C>T (p.Gln737Ter)SNV Pathogenic 575608 rs1569300538 X:18929007-18929007 X:18910889-18910889
7 PHKA2 NM_000292.3(PHKA2):c.1546C>T (p.Gln516Ter)SNV Pathogenic 649460 X:18943809-18943809 X:18925691-18925691
8 PHKA2 NM_000292.3(PHKA2):c.3331C>T (p.Arg1111Ter)SNV Pathogenic 655569 X:18913261-18913261 X:18895143-18895143
9 PHKA2 NM_000292.3(PHKA2):c.2268dup (p.Asp757Ter)duplication Pathogenic 694636 X:18927010-18927011 X:18908892-18908893
10 PHKA2 NM_000292.3(PHKA2):c.918+1G>ASNV Pathogenic 694638 X:18958112-18958112 X:18939994-18939994
11 PHKA2 NM_000292.3(PHKA2):c.718-2A>GSNV Pathogenic 694641 X:18959795-18959795 X:18941677-18941677
12 PHKA2 NM_000292.3(PHKA2):c.3397C>T (p.Gln1133Ter)SNV Pathogenic 803725 X:18912462-18912462 X:18894344-18894344
13 PHKA2 NM_000292.3(PHKA2):c.1138-2A>GSNV Pathogenic 803728 X:18949868-18949868 X:18931750-18931750
14 PHKA2 NM_000292.3(PHKA2):c.314_317del (p.Thr105fs)deletion Pathogenic 803730 X:18969359-18969362 X:18951241-18951244
15 PHKA2 NM_000292.3(PHKA2):c.235C>T (p.Gln79Ter)SNV Pathogenic 807651 X:18972374-18972374 X:18954256-18954256
16 PHKA2 NC_000023.11:g.(?_18929208)_(18983952_?)deldeletion Pathogenic 833058 X:18947326-19002070
17 PHKA2 NM_000292.3(PHKA2):c.3377C>A (p.Ser1126Ter)SNV Pathogenic 845671 X:18912482-18912482 X:18894364-18894364
18 PHKA2 NM_000292.3(PHKA2):c.3025C>T (p.Gln1009Ter)SNV Pathogenic 10527 rs137852285 X:18919605-18919605 X:18901487-18901487
19 PHKA2 NM_000292.3(PHKA2):c.2296C>T (p.Gln766Ter)SNV Pathogenic 10528 rs137852286 X:18926983-18926983 X:18908865-18908865
20 PHKA2 NM_000292.3(PHKA2):c.717+1G>TSNV Pathogenic 10529 rs587776731 X:18961827-18961827 X:18943709-18943709
21 PHKA2 NM_000292.3(PHKA2):c.3146C>A (p.Ser1049Ter)SNV Pathogenic 10530 rs137852287 X:18915417-18915417 X:18897299-18897299
22 PHKA2 NM_000292.3(PHKA2):c.3614C>T (p.Pro1205Leu)SNV Pathogenic 10531 rs137852288 X:18911697-18911697 X:18893579-18893579
23 PHKA2 NM_000292.3(PHKA2):c.421_423del (p.Phe141del)deletion Pathogenic 10532 rs587776732 X:18969253-18969255 X:18951135-18951137
24 PHKA2 NM_000292.3(PHKA2):c.896A>G (p.Asp299Gly)SNV Pathogenic 10534 rs137852289 X:18958135-18958135 X:18940017-18940017
25 PHKA2 NM_000292.3(PHKA2):c.395A>C (p.His132Pro)SNV Pathogenic 10536 rs137852291 X:18969281-18969281 X:18951163-18951163
26 PHKA2 NM_000292.3(PHKA2):c.394C>T (p.His132Tyr)SNV Pathogenic 10537 rs137852292 X:18969282-18969282 X:18951164-18951164
27 PHKA2 NM_000292.3(PHKA2):c.750_752del (p.Thr251del)deletion Pathogenic 10539 rs587776733 X:18959759-18959761 X:18941641-18941643
28 PHKA2 PHKA2, 6-BP INS, NT3331insertion Pathogenic 10540
29 PHKA2 NM_000292.3(PHKA2):c.565A>G (p.Lys189Glu)SNV Pathogenic 10541 rs137852295 X:18963249-18963249 X:18945131-18945131
30 PHKA2 NM_000292.3(PHKA2):c.133C>T (p.Arg45Trp)SNV Pathogenic/Likely pathogenic 644261 X:18972476-18972476 X:18954358-18954358
31 PHKA2 NM_000292.3(PHKA2):c.2746C>T (p.Arg916Trp)SNV Pathogenic/Likely pathogenic 593082 rs1569297427 X:18924673-18924673 X:18906555-18906555
32 PHKA2 NM_000292.3(PHKA2):c.884G>A (p.Arg295His)SNV Pathogenic/Likely pathogenic 208676 rs797044877 X:18958147-18958147 X:18940029-18940029
33 PHKA2 NM_000292.3(PHKA2):c.883C>T (p.Arg295Cys)SNV Likely pathogenic 208493 rs797045008 X:18958148-18958148 X:18940030-18940030
34 PHKA2 NM_000292.3(PHKA2):c.2597+1G>ASNV Likely pathogenic 566477 rs1210626722 X:18925135-18925135 X:18907017-18907017
35 PHKA2 NM_000292.3(PHKA2):c.-9_2del (p.Met1fs)deletion Likely pathogenic 567305 rs1569344469 X:19002049-19002059 X:18983931-18983941
36 PHKA2 NM_000292.3(PHKA2):c.1714+1G>ASNV Likely pathogenic 526620 rs1556002344 X:18942498-18942498 X:18924380-18924380
37 PHKA2 NM_000292.3(PHKA2):c.415T>C (p.Ser139Pro)SNV Likely pathogenic 522501 rs1556014969 X:18969261-18969261 X:18951143-18951143
38 PHKA2 NM_000292.3(PHKA2):c.3336+2T>ASNV Likely pathogenic 526621 rs1555988479 X:18913254-18913254 X:18895136-18895136
39 PHKA2 NM_000292.3(PHKA2):c.128G>C (p.Trp43Ser)SNV Likely pathogenic 488576 rs1556016365 X:18972481-18972481 X:18954363-18954363
40 PHKA2 NM_000292.3(PHKA2):c.1245G>T (p.Glu415Asp)SNV Likely pathogenic 694640 X:18949759-18949759 X:18931641-18931641
41 PHKA2 NM_000292.3(PHKA2):c.405_419delinsTCCTGGCC (p.Asp136fs)indel Likely pathogenic 694639 X:18969257-18969271 X:18951139-18951153
42 PHKA2 NM_000292.3(PHKA2):c.3644_3646dup (p.Thr1216_Arg1217insIle)duplication Likely pathogenic 841087 X:18911664-18911665 X:18893546-18893547
43 PHKA2 NM_000292.3(PHKA2):c.884G>T (p.Arg295Leu)SNV Likely pathogenic 803729 X:18958147-18958147 X:18940029-18940029
44 PHKA2 NM_000292.3(PHKA2):c.556C>T (p.Arg186Cys)SNV Likely pathogenic 10538 rs137852294 X:18963258-18963258 X:18945140-18945140
45 PHKA2 NM_000292.3(PHKA2):c.557G>A (p.Arg186His)SNV Likely pathogenic 10535 rs137852290 X:18963257-18963257 X:18945139-18945139
46 PHKA2 NM_000292.3(PHKA2):c.3341C>T (p.Thr1114Ile)SNV Likely pathogenic 10533 rs137852293 X:18912518-18912518 X:18894400-18894400
47 PHKA2 NM_000292.3(PHKA2):c.3371_3377dup (p.Val1127fs)duplication Likely pathogenic 858405 X:18912481-18912482 X:18894363-18894364
48 PHKA2 NM_000292.3(PHKA2):c.2518-1G>ASNV Likely pathogenic 851319 X:18925216-18925216 X:18907098-18907098
49 PHKA2 NC_000023.11:g.18895137dupduplication Likely pathogenic 839048 X:18913254-18913255 X:18895136-18895137
50 PHKA2 NM_000292.3(PHKA2):c.1042-1G>ASNV Likely pathogenic 841380 X:18954269-18954269 X:18936151-18936151

UniProtKB/Swiss-Prot genetic disease variations for Glycogen Storage Disease Ixa1:

73 (show all 17)
# Symbol AA change Variation ID SNP ID
1 PHKA2 p.His132Pro VAR_006177 rs137852291
2 PHKA2 p.His132Tyr VAR_006178 rs137852292
3 PHKA2 p.Arg186Cys VAR_006180 rs137852294
4 PHKA2 p.Arg186His VAR_006181 rs137852290
5 PHKA2 p.Asp299Gly VAR_006183 rs137852289
6 PHKA2 p.Thr1114Ile VAR_006185 rs137852293
7 PHKA2 p.Pro1205Leu VAR_006186 rs137852288
8 PHKA2 p.Lys189Glu VAR_012269 rs137852295
9 PHKA2 p.Gly193Val VAR_012271
10 PHKA2 p.Arg295His VAR_012272 rs797044877
11 PHKA2 p.Pro399Ser VAR_012273
12 PHKA2 p.Glu1125Lys VAR_012276 rs155598807
13 PHKA2 p.Gly1207Trp VAR_012277
14 PHKA2 p.Pro498Leu VAR_062394 rs199792389
15 PHKA2 p.Pro869Arg VAR_062395 rs777137574
16 PHKA2 p.Arg916Trp VAR_062396
17 PHKA2 p.Met1113Ile VAR_062398

Expression for Glycogen Storage Disease Ixa1

Search GEO for disease gene expression data for Glycogen Storage Disease Ixa1.

Pathways for Glycogen Storage Disease Ixa1

GO Terms for Glycogen Storage Disease Ixa1

Sources for Glycogen Storage Disease Ixa1

3 CDC
7 CNVD
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10 dbSNP
11 DGIdb
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56 OMIM
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63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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