D2HGA2
MCID: D2H003
MIFTS: 34

D-2-Hydroxyglutaric Aciduria 2 (D2HGA2)

Categories: Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for D-2-Hydroxyglutaric Aciduria 2

MalaCards integrated aliases for D-2-Hydroxyglutaric Aciduria 2:

Name: D-2-Hydroxyglutaric Aciduria 2 57 12 72 29 6 15 70
D2hga2 57 12 72
D-2-Hydroxyglutaric Aciduria, Type 2 39

Characteristics:

HPO:

31
d-2-hydroxyglutaric aciduria 2:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0111352
OMIM® 57 613657
OMIM Phenotypic Series 57 PS600721
MeSH 44 D020739
MedGen 41 C3150909
UMLS 70 C3150909

Summaries for D-2-Hydroxyglutaric Aciduria 2

UniProtKB/Swiss-Prot : 72 D-2-hydroxyglutaric aciduria 2: A neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2-hydroxyglutaric acid in the urine.

MalaCards based summary : D-2-Hydroxyglutaric Aciduria 2, also known as d2hga2, is related to d-2-hydroxyglutaric aciduria 1 and 2-hydroxyglutaric aciduria. An important gene associated with D-2-Hydroxyglutaric Aciduria 2 is IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2), and among its related pathways/superpathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Citrate cycle (TCA cycle). Related phenotypes are d-2-hydroxyglutaric aciduria and d-2-hydroxyglutaric acidemia

Disease Ontology : 12 A D-2-hydroxyglutaric aciduria that has material basis in heterozygous mutation in IDH2 on 15q26.1.

More information from OMIM: 613657 PS600721

Related Diseases for D-2-Hydroxyglutaric Aciduria 2

Graphical network of the top 20 diseases related to D-2-Hydroxyglutaric Aciduria 2:



Diseases related to D-2-Hydroxyglutaric Aciduria 2

Symptoms & Phenotypes for D-2-Hydroxyglutaric Aciduria 2

Human phenotypes related to D-2-Hydroxyglutaric Aciduria 2:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 d-2-hydroxyglutaric aciduria 31 very rare (1%) HP:0012321
2 d-2-hydroxyglutaric acidemia 31 very rare (1%) HP:0040146
3 global developmental delay 31 HP:0001263
4 cardiomyopathy 31 HP:0001638
5 seizure 31 HP:0001250
6 hypotonia 31 HP:0001252

Clinical features from OMIM®:

613657 (Updated 05-Apr-2021)

Drugs & Therapeutics for D-2-Hydroxyglutaric Aciduria 2

Search Clinical Trials , NIH Clinical Center for D-2-Hydroxyglutaric Aciduria 2

Genetic Tests for D-2-Hydroxyglutaric Aciduria 2

Genetic tests related to D-2-Hydroxyglutaric Aciduria 2:

# Genetic test Affiliating Genes
1 D-2-Hydroxyglutaric Aciduria 2 29 IDH2

Anatomical Context for D-2-Hydroxyglutaric Aciduria 2

Publications for D-2-Hydroxyglutaric Aciduria 2

Articles related to D-2-Hydroxyglutaric Aciduria 2:

# Title Authors PMID Year
1
IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. 6 57
20847235 2010
2
The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. 57 6
20171147 2010
3
Genetic dissection of leukemia-associated IDH1 and IDH2 mutants and D-2-hydroxyglutarate in Drosophila. 6
25398939 2015
4
Novel cases of D-2-hydroxyglutaric aciduria with IDH1 or IDH2 mosaic mutations identified by amplicon deep sequencing. 6
24049096 2013
5
Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. 6
23558173 2013
6
A lymphoblast model for IDH2 gain-of-function activity in d-2-hydroxyglutaric aciduria type II: novel avenues for biochemical and therapeutic studies. 6
21889589 2011
7
IDH1 and IDH2 mutations in gliomas. 57
19228619 2009
8
Computational approach to unravel the impact of missense mutations of proteins (D2HGDH and IDH2) causing D-2-hydroxyglutaric aciduria 2. 61
29987523 2018

Variations for D-2-Hydroxyglutaric Aciduria 2

ClinVar genetic disease variations for D-2-Hydroxyglutaric Aciduria 2:

6 (show all 38)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 IDH2 NM_001289910.1(IDH2):c.262C>G (p.Arg88Gly) SNV Pathogenic 14717 rs267606870 GRCh37: 15:90631935-90631935
GRCh38: 15:90088703-90088703
2 IDH2 NM_002168.4(IDH2):c.1359G>A (p.Ter453=) SNV Pathogenic 1033902 GRCh37: 15:90627498-90627498
GRCh38: 15:90084266-90084266
3 IDH2 NM_001289910.1(IDH2):c.263G>A (p.Arg88Gln) SNV Pathogenic/Likely pathogenic 14716 rs121913502 GRCh37: 15:90631934-90631934
GRCh38: 15:90088702-90088702
4 IDH2 NM_002168.4(IDH2):c.1039G>A (p.Ala347Thr) SNV Likely pathogenic 828158 rs767061831 GRCh37: 15:90628548-90628548
GRCh38: 15:90085316-90085316
5 IDH2 NM_001289910.1(IDH2):c.973C>T (p.Arg325Cys) SNV Uncertain significance 641910 rs765712414 GRCh37: 15:90628282-90628282
GRCh38: 15:90085050-90085050
6 IDH2 NM_001289910.1(IDH2):c.432C>G (p.Phe144Leu) SNV Uncertain significance 643998 rs758536587 GRCh37: 15:90631681-90631681
GRCh38: 15:90088449-90088449
7 IDH2 NM_001289910.1(IDH2):c.688A>G (p.Lys230Glu) SNV Uncertain significance 657276 rs771346231 GRCh37: 15:90630467-90630467
GRCh38: 15:90087235-90087235
8 IDH2 NM_002168.4(IDH2):c.1171C>T (p.Leu391Phe) SNV Uncertain significance 1042645 GRCh37: 15:90628240-90628240
GRCh38: 15:90085008-90085008
9 IDH2 NM_002168.4(IDH2):c.662T>C (p.Met221Thr) SNV Uncertain significance 1043109 GRCh37: 15:90631607-90631607
GRCh38: 15:90088375-90088375
10 IDH2 NM_002168.4(IDH2):c.207+5T>C SNV Uncertain significance 930818 GRCh37: 15:90634780-90634780
GRCh38: 15:90091548-90091548
11 IDH2 NM_002168.4(IDH2):c.293T>C (p.Ile98Thr) SNV Uncertain significance 837402 GRCh37: 15:90633791-90633791
GRCh38: 15:90090559-90090559
12 IDH2 NM_002168.4(IDH2):c.723G>C (p.Gln241His) SNV Uncertain significance 948060 GRCh37: 15:90630763-90630763
GRCh38: 15:90087531-90087531
13 IDH2 NM_002168.4(IDH2):c.137T>A (p.Val46Glu) SNV Uncertain significance 835500 GRCh37: 15:90634855-90634855
GRCh38: 15:90091623-90091623
14 IDH2 NM_002168.4(IDH2):c.227A>G (p.Asp76Gly) SNV Uncertain significance 959646 GRCh37: 15:90633857-90633857
GRCh38: 15:90090625-90090625
15 IDH2 NM_002168.4(IDH2):c.373+5G>A SNV Uncertain significance 1030527 GRCh37: 15:90633706-90633706
GRCh38: 15:90090474-90090474
16 IDH2 NM_002168.4(IDH2):c.877A>C (p.Met293Leu) SNV Uncertain significance 1030528 GRCh37: 15:90630434-90630434
GRCh38: 15:90087202-90087202
17 IDH2-DT , IDH2 NM_002168.3(IDH2):c.23T>C (p.Val8Ala) SNV Uncertain significance 559362 rs369445642 GRCh37: 15:90645600-90645600
GRCh38: 15:90102368-90102368
18 IDH2 NM_002168.4(IDH2):c.1354C>G (p.Gln452Glu) SNV Uncertain significance 934685 GRCh37: 15:90627503-90627503
GRCh38: 15:90084271-90084271
19 IDH2 NM_002168.4(IDH2):c.1259A>T (p.His420Leu) SNV Uncertain significance 1010519 GRCh37: 15:90628060-90628060
GRCh38: 15:90084828-90084828
20 IDH2 NM_002168.4(IDH2):c.923G>C (p.Cys308Ser) SNV Uncertain significance 949037 GRCh37: 15:90630388-90630388
GRCh38: 15:90087156-90087156
21 IDH2 NM_002168.4(IDH2):c.276T>C (p.Thr92=) SNV Likely benign 728479 rs774212594 GRCh37: 15:90633808-90633808
GRCh38: 15:90090576-90090576
22 IDH2 NM_002168.4(IDH2):c.1003G>A (p.Val335Ile) SNV Likely benign 789533 rs140596855 GRCh37: 15:90628584-90628584
GRCh38: 15:90085352-90085352
23 IDH2 NM_002168.4(IDH2):c.535-6C>T SNV Likely benign 760764 rs760220786 GRCh37: 15:90631740-90631740
GRCh38: 15:90088508-90088508
24 IDH2 NM_001289910.1(IDH2):c.517G>A (p.Asp173Asn) SNV Likely benign 211176 rs142816010 GRCh37: 15:90631596-90631596
GRCh38: 15:90088364-90088364
25 IDH2 NM_001289910.1(IDH2):c.204G>A (p.Glu68=) SNV Likely benign 435489 rs536071174 GRCh37: 15:90633724-90633724
GRCh38: 15:90090492-90090492
26 IDH2 NM_002168.4(IDH2):c.141G>A (p.Ala47=) SNV Likely benign 712843 rs145802942 GRCh37: 15:90634851-90634851
GRCh38: 15:90091619-90091619
27 IDH2 NM_002168.4(IDH2):c.120C>T (p.Ala40=) SNV Likely benign 715534 rs148974231 GRCh37: 15:90634872-90634872
GRCh38: 15:90091640-90091640
28 IDH2 NM_001289910.1(IDH2):c.882C>T (p.Ala294=) SNV Benign 211173 rs190078206 GRCh37: 15:90628549-90628549
GRCh38: 15:90085317-90085317
29 IDH2 NM_001289910.1(IDH2):c.171G>A (p.Val57=) SNV Benign 158665 rs150943639 GRCh37: 15:90633757-90633757
GRCh38: 15:90090525-90090525
30 IDH2 NM_001289910.1(IDH2):c.1148C>T (p.Thr383Met) SNV Benign 158664 rs118053940 GRCh37: 15:90627553-90627553
GRCh38: 15:90084321-90084321
31 IDH2 NM_001289910.1(IDH2):c.626G>A (p.Arg209His) SNV Benign 211177 rs118101777 GRCh37: 15:90630704-90630704
GRCh38: 15:90087472-90087472
32 IDH2 NM_002168.4(IDH2):c.207+4G>A SNV Benign 788184 rs77995170 GRCh37: 15:90634781-90634781
GRCh38: 15:90091549-90091549
33 IDH2 NM_001289910.1(IDH2):c.273G>C (p.Leu91=) SNV Benign 211175 rs144712130 GRCh37: 15:90631924-90631924
GRCh38: 15:90088692-90088692
34 IDH2 NM_001289910.1(IDH2):c.783A>G (p.Gly261=) SNV Benign 158667 rs16943901 GRCh37: 15:90630372-90630372
GRCh38: 15:90087140-90087140
35 IDH2 NM_002168.4(IDH2):c.942T>C (p.Asp314=) SNV Benign 758347 rs142721369 GRCh37: 15:90630369-90630369
GRCh38: 15:90087137-90087137
36 IDH2 NM_001289910.1(IDH2):c.894C>T (p.Thr298=) SNV Benign 158663 rs11540478 GRCh37: 15:90628537-90628537
GRCh38: 15:90085305-90085305
37 IDH2 NM_002168.4(IDH2):c.1302C>G (p.Thr434=) SNV Benign 791742 rs150574164 GRCh37: 15:90627555-90627555
GRCh38: 15:90084323-90084323
38 IDH2 NM_001289910.1(IDH2):c.837G>A (p.Thr279=) SNV Benign 158668 rs61737002 GRCh37: 15:90628594-90628594
GRCh38: 15:90085362-90085362

UniProtKB/Swiss-Prot genetic disease variations for D-2-Hydroxyglutaric Aciduria 2:

72
# Symbol AA change Variation ID SNP ID
1 IDH2 p.Arg140Gly VAR_065174 rs267606870
2 IDH2 p.Arg140Gln VAR_065175 rs121913502

Expression for D-2-Hydroxyglutaric Aciduria 2

Search GEO for disease gene expression data for D-2-Hydroxyglutaric Aciduria 2.

Pathways for D-2-Hydroxyglutaric Aciduria 2

GO Terms for D-2-Hydroxyglutaric Aciduria 2

Cellular components related to D-2-Hydroxyglutaric Aciduria 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.35 L2HGDH IDH3G IDH2 D2HGDH ADHFE1
2 mitochondrial matrix GO:0005759 8.92 IDH3G IDH2 D2HGDH ADHFE1

Biological processes related to D-2-Hydroxyglutaric Aciduria 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.35 L2HGDH IDH3G IDH2 D2HGDH ADHFE1
2 tricarboxylic acid cycle GO:0006099 9.26 IDH3G IDH2
3 isocitrate metabolic process GO:0006102 9.16 IDH3G IDH2
4 2-oxoglutarate metabolic process GO:0006103 8.92 L2HGDH IDH2 D2HGDH ADHFE1

Molecular functions related to D-2-Hydroxyglutaric Aciduria 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor GO:0016616 9.16 IDH3G IDH2
2 NAD binding GO:0051287 8.96 IDH3G IDH2
3 oxidoreductase activity GO:0016491 8.92 L2HGDH IDH2 D2HGDH ADHFE1

Sources for D-2-Hydroxyglutaric Aciduria 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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