D2HGA1
MCID: D2H002
MIFTS: 52

D-2-Hydroxyglutaric Aciduria 1 (D2HGA1)

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

Aliases & Classifications for D-2-Hydroxyglutaric Aciduria 1

MalaCards integrated aliases for D-2-Hydroxyglutaric Aciduria 1:

Name: D-2-Hydroxyglutaric Aciduria 1 57 12 73 29 6 71
D-2-Hydroxyglutaric Aciduria 57 12 20 58 36 29 13 6 15 39 71
D2hga1 57 12 73
D-2-Hydroxyglutaric Acidemia 20 58
D-2-Hga 20 58
D2ha 20 73
Combined D-2- and L-2-Hydroxyglutaric Aciduria 71
Aciduria, D-2-Hydroxyglutaric, Type 1 39
D2hga 57

Characteristics:

Orphanet epidemiological data:

58
d-2-hydroxyglutaric aciduria
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
two different phenotypes exist - severe phenotype (early infantile onset, epileptic encephalopathy and often cardiomyopathy) and mild phenotype (more variable clinical presentation)
severe phenotype onset - neonate
mild phenotype onset - 11-18 months


HPO:

31
d-2-hydroxyglutaric aciduria 1:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0050575 DOID:0111351
OMIM® 57 600721
OMIM Phenotypic Series 57 PS600721
KEGG 36 H01225
MeSH 44 D020739
ICD10 via Orphanet 33 E72.8
Orphanet 58 ORPHA79315
UMLS 71 C1833429 C2746066 C3152055

Summaries for D-2-Hydroxyglutaric Aciduria 1

GARD : 20 D-2-alpha hydroxyglutaric aciduria is an inherited metabolic condition that is associated with progressive brain damage. Signs and symptoms of this condition include developmental delay, seizures, hypotonia, and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory. D-2-alpha hydroxyglutaric aciduria is caused by changes (mutations) in the D2HGDH gene and is inherited in an autosomal recessive manner. Treatment is focused on alleviating the signs and symptoms of the condition, such as medications to control seizures.

MalaCards based summary : D-2-Hydroxyglutaric Aciduria 1, also known as d-2-hydroxyglutaric aciduria, is related to d-2-hydroxyglutaric aciduria 2 and combined d-2- and l-2-hydroxyglutaric aciduria, and has symptoms including seizures, muscle weakness and dyspnea. An important gene associated with D-2-Hydroxyglutaric Aciduria 1 is D2HGDH (D-2-Hydroxyglutarate Dehydrogenase), and among its related pathways/superpathways are Citrate cycle (TCA cycle) and Glutathione metabolism. Affiliated tissues include cortex, skeletal muscle and cerebellum, and related phenotypes are macrocephaly and intellectual disability

Disease Ontology : 12 An 2-hydroxyglutaric aciduria that involves developmental delay, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory.

OMIM® : 57 D-2-hydroxyglutaric aciduria is a neurometabolic disorder first described by Chalmers et al. (1980). Clinical symptoms include developmental delay, epilepsy, hypotonia, and dysmorphic features. Mild and severe phenotypes were characterized (van der Knaap et al., 1999). The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and, often, cardiomyopathy. The mild phenotype has a more variable clinical presentation. (600721) (Updated 05-Mar-2021)

KEGG : 36 D-2-hydroxyglutaric aciduria (D-2-HGA) is an autosomal recessive neurometabolic disorder. Clinical symptoms of D-2-HGA are developmental delay, epilepsy, hypotonia, and dysmorphic features. It has been suggested that mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. Recently, IDH2 mutations in patients with D-2-HGA were reported.

UniProtKB/Swiss-Prot : 73 D-2-hydroxyglutaric aciduria 1: A rare recessive 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.

Related Diseases for D-2-Hydroxyglutaric Aciduria 1

Diseases in the D-2-Hydroxyglutaric Aciduria 1 family:

L-2-Hydroxyglutaric Aciduria D-2-Hydroxyglutaric Aciduria 2
2-Hydroxyglutaric Aciduria

Diseases related to D-2-Hydroxyglutaric Aciduria 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 73)
# Related Disease Score Top Affiliating Genes
1 d-2-hydroxyglutaric aciduria 2 33.0 L2HGDH IDH3G IDH2 D2HGDH ADHFE1
2 combined d-2- and l-2-hydroxyglutaric aciduria 32.4 SLC25A1 L2HGDH KDM4C IDH2 D2HGDH ADHFE1
3 l-2-hydroxyglutaric aciduria 29.6 SLC25A1 L2HGDH KDM4C IDH2 IDH1 GCDH
4 2-hydroxyglutaric aciduria 28.6 SLC25A1 L2HGDH KDM4C IDH3G IDH3A IDH2
5 metaphyseal enchondromatosis with d-2-hydroxyglutaric aciduria 11.8
6 hypotonia 10.7
7 organic acidemia 10.5
8 yemenite deaf-blind hypopigmentation syndrome 10.5
9 cortical blindness 10.5
10 enchondroma 10.4 IDH2 IDH1
11 adult brain stem glioma 10.3 IDH2 IDH1
12 cytogenetically normal acute myeloid leukemia 10.3 IDH2 IDH1
13 periosteal chondrosarcoma 10.3 IDH2 IDH1
14 adult oligodendroglioma 10.3 IDH2 IDH1
15 atrial standstill 1 10.3
16 encephalopathy 10.3
17 childhood oligodendroglioma 10.3 IDH2 IDH1
18 gemistocytic astrocytoma 10.3 IDH2 IDH1
19 adult astrocytic tumour 10.3 IDH2 IDH1
20 mixed oligodendroglioma-astrocytoma 10.3 IDH2 IDH1
21 mixed glioma 10.3 IDH2 IDH1
22 low grade glioma 10.2 IDH2 IDH1
23 chondroblastic osteosarcoma 10.2 L2HGDH IDH2 IDH1
24 brain stem glioma 10.2 KDM4C IDH2 IDH1
25 inhibited female orgasm 10.2 IDH3G IDH3A
26 enchondromatosis, multiple, ollier type 10.2 KDM4C IDH2 IDH1
27 diffuse astrocytoma 10.2 KDM4C IDH2 IDH1
28 spindle cell hemangioma 10.2 IDH2 IDH1
29 brain glioma 10.2 KDM4C IDH2 IDH1
30 bile duct adenocarcinoma 10.2 KDM4C IDH2 IDH1
31 brain stem cancer 10.2 KDM4C IDH1
32 bone sarcoma 10.2 KDM4C IDH2 IDH1
33 leukemia, acute myeloid 10.2
34 autosomal recessive disease 10.2
35 leukemia 10.2
36 pyloric stenosis 10.2
37 mucopolysaccharidosis iii 10.2
38 dilated cardiomyopathy 10.2
39 hemangioma 10.2
40 myopathy 10.2
41 egg allergy 10.2
42 angiokeratoma 10.2
43 peripheral nervous system disease 10.2
44 angiokeratoma circumscriptum 10.2
45 myeloid leukemia 10.2
46 neuropathy 10.2
47 cerebral visual impairment 10.2
48 cerebral organic aciduria 10.2
49 neurometabolic disease 10.2
50 cardiogenic shock 10.2

Graphical network of the top 20 diseases related to D-2-Hydroxyglutaric Aciduria 1:



Diseases related to D-2-Hydroxyglutaric Aciduria 1

Symptoms & Phenotypes for D-2-Hydroxyglutaric Aciduria 1

Human phenotypes related to D-2-Hydroxyglutaric Aciduria 1:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 31 HP:0000256
2 intellectual disability 31 HP:0001249
3 frontal bossing 31 HP:0002007
4 muscle weakness 31 HP:0001324
5 global developmental delay 31 HP:0001263
6 prominent forehead 31 HP:0011220
7 micrognathia 31 HP:0000347
8 apnea 31 HP:0002104
9 cardiomyopathy 31 HP:0001638
10 aortic regurgitation 31 HP:0001659
11 generalized hypotonia 31 HP:0001290
12 multifocal cerebral white matter abnormalities 31 HP:0007052
13 episodic vomiting 31 HP:0002572
14 inspiratory stridor 31 HP:0005348
15 delayed cns myelination 31 HP:0002188
16 dilation of lateral ventricles 31 HP:0006956
17 subependymal cysts 31 HP:0002416
18 infantile encephalopathy 31 HP:0007105
19 glutaric aciduria 31 HP:0003150
20 seizure 31 HP:0001250
21 hypotonia 31 HP:0001252
22 d-2-hydroxyglutaric aciduria 31 HP:0012321

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Head And Neck Head:
macrocephaly

Muscle Soft Tissue:
muscle weakness

Laboratory Abnormalities:
d-2-hydroxyglutaric aciduria
elevated d-2-hydroxyglutaric acid (urine, plasma, csf)
elevated l-2-hydroxyglutaric acid (urine)
elevated 2-ketoglutarate (urine)

Respiratory:
inspiratory stridor (severe form)
apnea (severe form)

Neurologic Central Nervous System:
seizures
multifocal cerebral white matter abnormalities
delayed myelination
subependymal cysts
hypotonia
more
Head And Neck Face:
prominent forehead
micrognathia

Cardiovascular Heart:
aortic insufficiency
cardiomyopathy (severe form)

Abdomen Gastrointestinal:
episodic vomiting (severe form)

Clinical features from OMIM®:

600721 (Updated 05-Mar-2021)

UMLS symptoms related to D-2-Hydroxyglutaric Aciduria 1:


seizures, muscle weakness, dyspnea, stridor

GenomeRNAi Phenotypes related to D-2-Hydroxyglutaric Aciduria 1 according to GeneCards Suite gene sharing:

26 (show all 28)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-115 9.98 ADHFE1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-129 9.98 GK2
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-143 9.98 GAMT
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.98 GAMT
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-168 9.98 HIF1A
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-176 9.98 GK2
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 9.98 ADHFE1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-191 9.98 GAMT
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-199 9.98 ADHFE1
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-20 9.98 GAMT
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-200 9.98 HIF1A
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-214 9.98 GAMT
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-43 9.98 GK2
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-63 9.98 GAMT
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-67 9.98 GAMT
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-77 9.98 ADHFE1 GAMT GK2
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-79 9.98 HIF1A
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-81 9.98 ADHFE1
19 Decreased shRNA abundance (Z-score < -2) GR00366-A-9 9.98 GAMT
20 Decreased viability GR00055-A-1 9.53 GJB1
21 Decreased viability GR00055-A-2 9.53 GJB1
22 Decreased viability GR00221-A-1 9.53 GK2
23 Decreased viability GR00221-A-2 9.53 GK2
24 Decreased viability GR00221-A-4 9.53 GK2
25 Decreased viability GR00249-S 9.53 ETFA G6PC3 GJB1 IDH1 IDH3B
26 Decreased viability GR00381-A-1 9.53 L2HGDH
27 Decreased viability GR00386-A-1 9.53 IDH3A IDH3B
28 Decreased viability GR00402-S-2 9.53 D2HGDH G6PC3 GJB1

Drugs & Therapeutics for D-2-Hydroxyglutaric Aciduria 1

Search Clinical Trials , NIH Clinical Center for D-2-Hydroxyglutaric Aciduria 1

Genetic Tests for D-2-Hydroxyglutaric Aciduria 1

Genetic tests related to D-2-Hydroxyglutaric Aciduria 1:

# Genetic test Affiliating Genes
1 D-2-Hydroxyglutaric Aciduria 1 29 D2HGDH
2 D-2-Hydroxyglutaric Aciduria 29

Anatomical Context for D-2-Hydroxyglutaric Aciduria 1

MalaCards organs/tissues related to D-2-Hydroxyglutaric Aciduria 1:

40
Cortex, Skeletal Muscle, Cerebellum, Myeloid

Publications for D-2-Hydroxyglutaric Aciduria 1

Articles related to D-2-Hydroxyglutaric Aciduria 1:

(show top 50) (show all 73)
# Title Authors PMID Year
1
Mutations in phenotypically mild D-2-hydroxyglutaric aciduria. 6 61 57
16037974 2005
2
Phenotypic heterogeneity in the presentation of D-2-hydroxyglutaric aciduria in monozygotic twins. 61 57 6
16081310 2005
3
Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. 61 57 6
15609246 2005
4
D-2-hydroxyglutaric aciduria in a newborn with neurological abnormalities: a new neurometabolic disorder? 57 6 61
7609436 1993
5
Novel cases of D-2-hydroxyglutaric aciduria with IDH1 or IDH2 mosaic mutations identified by amplicon deep sequencing. 61 6
24049096 2013
6
Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria. 57 61
20020533 2010
7
D-2-hydroxyglutaric aciduria: a case with an intermediate phenotype and prenatal diagnosis of two affected fetuses. 57 61
12884432 2003
8
Spondyloenchondromatosis with D-2-hydroxyglutaric aciduria: a report of a second patient with this unusual combination. 61 57
12868470 2003
9
D-2-hydroxyglutaric aciduria in association with spondyloenchondromatosis. 61 57
10883451 2000
10
Facial anomalies in D-2-hydroxyglutaric aciduria. 61 57
10449646 1999
11
D-2-hydroxyglutaric aciduria: further clinical delineation. 61 57
10407777 1999
12
D-2-hydroxyglutaric aciduria. 61 57
7782605 1995
13
D-2-hydroxyglutaric aciduria: case report and biochemical studies. 57 61
6774165 1980
14
Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. 6
23558173 2013
15
The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. 6
20171147 2010
16
Metaphyseal enchondrodysplasia with 2-hydroxy-glutaric aciduria: observation of a third case and further delineation. 57
15602086 2005
17
Structure, substrate specificity, and catalytic mechanism of human D-2-HGDH and insights into pathogenicity of disease-associated mutations. 61
33431826 2021
18
Seizures and early onset dementia: D2HGA1 inborn error of metabolism in adults. 61
32857435 2020
19
IDH1 mutated acute myeloid leukemia in a child with metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria. 61
32166993 2020
20
Inborn errors of metabolite repair. 61
31691304 2020
21
Biochemical characterization of human D-2-hydroxyglutarate dehydrogenase and two disease related variants reveals the molecular cause of D-2-hydroxyglutaric aciduria. 61
31349060 2019
22
D-2-Hydroxyglutaric Aciduria with Enchondromatosis and Angiokeratoma Circumscriptum. 61
31890366 2019
23
D-2-hydroxyglutaric aciduria in a patient with speech delay due to a novel homozygous deletion in the D2HGDH gene. 61
31431883 2019
24
D-2-hydroxyglutaric aciduria Type I: Functional analysis of D2HGDH missense variants. 61
30908763 2019
25
Widespread and debilitating hemangiomas in a patient with enchondromatosis and D-2-hydroxyglutaric aciduria. 61
29744569 2018
26
Computational approach to unravel the impact of missense mutations of proteins (D2HGDH and IDH2) causing D-2-hydroxyglutaric aciduria 2. 61
29987523 2018
27
A small molecule inhibitor of mutant IDH2 rescues cardiomyopathy in a D-2-hydroxyglutaric aciduria type II mouse model. 61
27469509 2016
28
The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in oncogenesis and survival prolongation. 61
24880135 2014
29
Disruption of redox homeostasis and histopathological alterations caused by in vivo intrastriatal administration of D-2-hydroxyglutaric acid to young rats. 61
25043325 2014
30
Child Neurology: cognitive delay in a 7-year-old girl. 61
24218321 2013
31
Metaphyseal chondromatosis combined with D-2-hydroxyglutaric aciduria in four patients. 61
22639207 2012
32
IDH1 and IDH2 have critical roles in 2-hydroxyglutarate production in D-2-hydroxyglutarate dehydrogenase depleted cells. 61
22683334 2012
33
Progress in understanding 2-hydroxyglutaric acidurias. 61
22391998 2012
34
Whole-exome sequencing detects somatic mutations of IDH1 in metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA). 61
22025298 2011
35
A lymphoblast model for IDH2 gain-of-function activity in d-2-hydroxyglutaric aciduria type II: novel avenues for biochemical and therapeutic studies. 61
21889589 2011
36
Co-morbidity of Sanfilippo syndrome type C and D-2-hydroxyglutaric aciduria. 61
21384162 2011
37
Metabolic syndromes and malignant transformation: where the twain shall meet. 61
20962328 2010
38
IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. 61
20847235 2010
39
Peripheral neuropathy in a patient with D-2-hydroxyglutaric aciduria. 61
19169842 2009
40
[D-2-hydroxyglutaric aciduria. Report of two cases]. 61
19961059 2009
41
Measurement of D: -2-hydroxyglutarate dehydrogenase activity in cell homogenates derived from D: -2-hydroxyglutaric aciduria patients. 61
19283509 2009
42
D-2-hydroxyglutaric aciduria in three patients with proven SSADH deficiency: genetic coincidence or a related biochemical epiphenomenon? 61
16442322 2006
43
D-2-Hydroxyglutaric aciduria: unravelling the biochemical pathway and the genetic defect. 61
16601864 2006
44
Mitochondrial energy metabolism is markedly impaired by D-2-hydroxyglutaric acid in rat tissues. 61
15963747 2005
45
Kinetic characterization of human hydroxyacid-oxoacid transhydrogenase: relevance to D-2-hydroxyglutaric and gamma-hydroxybutyric acidurias. 61
16435184 2005
46
Measurement of urinary D- and L-2-hydroxyglutarate enantiomers by stable-isotope-dilution liquid chromatography-tandem mass spectrometry after derivatization with diacetyl-L-tartaric anhydride. 61
15166110 2004
47
D-2-hydroxyglutaric aciduria and glutaric aciduria type 1 in siblings: coincidence, or linked disorders? 61
15248096 2004
48
In vitro effects of D-2-hydroxyglutaric acid on glutamate binding, uptake and release in cerebral cortex of rats. 61
14706223 2004
49
Investigations by mass isotopomer analysis of the formation of D-2-hydroxyglutarate by cultured lymphoblasts from two patients with D-2-hydroxyglutaric aciduria. 61
14741351 2004
50
Inhibition of creatine kinase activity from rat cerebral cortex by D-2-hydroxyglutaric acid in vitro. 61
12963087 2004

Variations for D-2-Hydroxyglutaric Aciduria 1

ClinVar genetic disease variations for D-2-Hydroxyglutaric Aciduria 1:

6 (show top 50) (show all 181)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 D2HGDH NM_152783.5(D2HGDH):c.1331T>C (p.Val444Ala) SNV Pathogenic 1852 rs121434360 2:242707149-242707149 2:241767734-241767734
2 D2HGDH NM_152783.5(D2HGDH):c.440T>G (p.Ile147Ser) SNV Pathogenic 1853 rs121434361 2:242681939-242681939 2:241742524-241742524
3 D2HGDH NM_152783.5(D2HGDH):c.293-23A>G SNV Pathogenic 1854 rs145731647 2:242680425-242680425 2:241741010-241741010
4 D2HGDH NM_152783.5(D2HGDH):c.685-2A>G SNV Pathogenic 1855 rs753528947 2:242684122-242684122 2:241744707-241744707
5 D2HGDH NM_152783.5(D2HGDH):c.1315A>G (p.Asn439Asp) SNV Pathogenic 1856 rs121434362 2:242707133-242707133 2:241767718-241767718
6 D2HGDH NM_152783.5(D2HGDH):c.325_326dup (p.Glu110fs) Duplication Pathogenic 1857 rs749330477 2:242680479-242680480 2:241741064-241741065
7 D2HGDH NM_152783.5(D2HGDH):c.1123G>T (p.Asp375Tyr) SNV Pathogenic 1858 rs267606759 2:242690786-242690786 2:241751371-241751371
8 IDH2 NM_001289910.1(IDH2):c.262C>G (p.Arg88Gly) SNV Pathogenic 14717 rs267606870 15:90631935-90631935 15:90088703-90088703
9 D2HGDH NM_152783.5(D2HGDH):c.1027del (p.Ser343fs) Deletion Pathogenic 210809 rs797045506 2:242690689-242690689 2:241751274-241751274
10 D2HGDH NC_000002.12:g.(?_241741010)_(241767989_?)del Deletion Pathogenic 539292 2:242680425-242707404 2:241741010-241767989
11 D2HGDH NM_152783.5(D2HGDH):c.642del (p.Arg215fs) Deletion Pathogenic 572875 rs1559361049 2:242683187-242683187 2:241743772-241743772
12 IDH2 NM_001289910.1(IDH2):c.263G>A (p.Arg88Gln) SNV Pathogenic/Likely pathogenic 14716 rs121913502 15:90631934-90631934 15:90088702-90088702
13 D2HGDH NM_152783.5(D2HGDH):c.1306+2T>C SNV Likely pathogenic 210815 rs797045507 2:242695431-242695431 2:241756016-241756016
14 D2HGDH NM_152783.5(D2HGDH):c.853+2T>C SNV Likely pathogenic 570363 rs1559364994 2:242684294-242684294 2:241744879-241744879
15 IDH2 NM_002168.4(IDH2):c.1039G>A (p.Ala347Thr) SNV Likely pathogenic 828158 rs767061831 15:90628548-90628548 15:90085316-90085316
16 D2HGDH NM_152783.5(D2HGDH):c.963C>T (p.Val321=) SNV Conflicting interpretations of pathogenicity 737190 rs141524359 2:242689675-242689675 2:241750260-241750260
17 D2HGDH NM_152783.5(D2HGDH):c.1258G>A (p.Ala420Thr) SNV Conflicting interpretations of pathogenicity 158409 rs149504235 2:242695381-242695381 2:241755966-241755966
18 D2HGDH NM_152783.5(D2HGDH):c.566C>T (p.Pro189Leu) SNV Conflicting interpretations of pathogenicity 158422 rs587783517 2:242683112-242683112 2:241743697-241743697
19 D2HGDH NM_152783.5(D2HGDH):c.517G>A (p.Val173Ile) SNV Conflicting interpretations of pathogenicity 432634 rs146408017 2:242683063-242683063 2:241743648-241743648
20 D2HGDH NM_152783.5(D2HGDH):c.1140+8G>A SNV Conflicting interpretations of pathogenicity 210813 rs369135156 2:242690811-242690811 2:241751396-241751396
21 IDH2 NM_001289910.1(IDH2):c.973C>T (p.Arg325Cys) SNV Uncertain significance 641910 rs765712414 15:90628282-90628282 15:90085050-90085050
22 D2HGDH NM_152783.5(D2HGDH):c.1446G>A (p.Lys482=) SNV Uncertain significance 746005 rs763276027 2:242707264-242707264 2:241767849-241767849
23 D2HGDH NM_152783.5(D2HGDH):c.*405C>T SNV Uncertain significance 898495 2:242707789-242707789 2:241768374-241768374
24 D2HGDH NM_152783.5(D2HGDH):c.*461C>T SNV Uncertain significance 898497 2:242707845-242707845 2:241768430-241768430
25 D2HGDH NM_152783.5(D2HGDH):c.*462G>A SNV Uncertain significance 898498 2:242707846-242707846 2:241768431-241768431
26 IDH2 NM_002168.4(IDH2):c.207+5T>C SNV Uncertain significance 930818 15:90634780-90634780 15:90091548-90091548
27 IDH2 NM_002168.4(IDH2):c.1354C>G (p.Gln452Glu) SNV Uncertain significance 934685 15:90627503-90627503 15:90084271-90084271
28 D2HGDH NM_152783.5(D2HGDH):c.1334C>T (p.Thr445Met) SNV Uncertain significance 935524 2:242707152-242707152 2:241767737-241767737
29 D2HGDH NM_152783.5(D2HGDH):c.740C>T (p.Thr247Met) SNV Uncertain significance 942698 2:242684179-242684179 2:241744764-241744764
30 IDH2 NM_002168.4(IDH2):c.723G>C (p.Gln241His) SNV Uncertain significance 948060 15:90630763-90630763 15:90087531-90087531
31 IDH2 NM_002168.4(IDH2):c.923G>C (p.Cys308Ser) SNV Uncertain significance 949037 15:90630388-90630388 15:90087156-90087156
32 D2HGDH NM_152783.5(D2HGDH):c.1054G>C (p.Glu352Gln) SNV Uncertain significance 949950 2:242690717-242690717 2:241751302-241751302
33 IDH2 NM_002168.4(IDH2):c.227A>G (p.Asp76Gly) SNV Uncertain significance 959646 15:90633857-90633857 15:90090625-90090625
34 D2HGDH NM_152783.5(D2HGDH):c.1528A>G (p.Ile510Val) SNV Uncertain significance 973466 2:242707346-242707346 2:241767931-241767931
35 D2HGDH NM_152783.5(D2HGDH):c.-92-2A>T SNV Uncertain significance 631852 rs1559333243 2:242674546-242674546 2:241735131-241735131
36 D2HGDH NM_152783.5(D2HGDH):c.998-2A>G SNV Uncertain significance 631853 rs1559380854 2:242690659-242690659 2:241751244-241751244
37 D2HGDH NM_152783.5(D2HGDH):c.1256G>A (p.Arg419His) SNV Uncertain significance 631854 rs199908032 2:242695379-242695379 2:241755964-241755964
38 IDH2 NM_001289910.1(IDH2):c.432C>G (p.Phe144Leu) SNV Uncertain significance 643998 rs758536587 15:90631681-90631681 15:90088449-90088449
39 D2HGDH NM_152783.5(D2HGDH):c.1127A>G (p.Gln376Arg) SNV Uncertain significance 648621 rs1575286670 2:242690790-242690790 2:241751375-241751375
40 D2HGDH NM_152783.5(D2HGDH):c.1370T>C (p.Leu457Pro) SNV Uncertain significance 649282 rs1575352566 2:242707188-242707188 2:241767773-241767773
41 D2HGDH NM_152783.5(D2HGDH):c.1421C>T (p.Ala474Val) SNV Uncertain significance 653495 rs369324431 2:242707239-242707239 2:241767824-241767824
42 IDH2 NM_001289910.1(IDH2):c.688A>G (p.Lys230Glu) SNV Uncertain significance 657276 rs771346231 15:90630467-90630467 15:90087235-90087235
43 D2HGDH NM_152783.5(D2HGDH):c.659A>G (p.His220Arg) SNV Uncertain significance 662655 rs112424377 2:242683205-242683205 2:241743790-241743790
44 D2HGDH NM_152783.5(D2HGDH):c.1353del (p.Ser452fs) Deletion Uncertain significance 579877 rs1559404382 2:242707168-242707168 2:241767753-241767753
45 GJB1 NM_000166.6(GJB1):c.425G>A (p.Arg142Gln) SNV Uncertain significance 188174 rs786204123 X:70443982-70443982 X:71224132-71224132
46 IDH2-DT NM_002168.3(IDH2):c.23T>C (p.Val8Ala) SNV Uncertain significance 559362 rs369445642 15:90645600-90645600 15:90102368-90102368
47 D2HGDH NM_152783.5(D2HGDH):c.*503C>T SNV Uncertain significance 335341 rs755235230 2:242707887-242707887 2:241768472-241768472
48 D2HGDH NM_152783.5(D2HGDH):c.1357C>T (p.Leu453Phe) SNV Uncertain significance 335319 rs145839736 2:242707175-242707175 2:241767760-241767760
49 D2HGDH NM_152783.5(D2HGDH):c.*597C>T SNV Uncertain significance 335343 rs187157907 2:242707981-242707981 2:241768566-241768566
50 D2HGDH NM_152783.5(D2HGDH):c.454C>T (p.Arg152Cys) SNV Uncertain significance 335312 rs201926349 2:242681953-242681953 2:241742538-241742538

UniProtKB/Swiss-Prot genetic disease variations for D-2-Hydroxyglutaric Aciduria 1:

73
# Symbol AA change Variation ID SNP ID
1 D2HGDH p.Ile147Ser VAR_025890 rs121434361
2 D2HGDH p.Asp375Tyr VAR_025891 rs267606759
3 D2HGDH p.Asn439Asp VAR_025893 rs121434362
4 D2HGDH p.Val444Ala VAR_025894 rs121434360

Expression for D-2-Hydroxyglutaric Aciduria 1

Search GEO for disease gene expression data for D-2-Hydroxyglutaric Aciduria 1.

Pathways for D-2-Hydroxyglutaric Aciduria 1

Pathways related to D-2-Hydroxyglutaric Aciduria 1 according to KEGG:

36
# Name Kegg Source Accession
1 Citrate cycle (TCA cycle) hsa00020
2 Glutathione metabolism hsa00480

Pathways related to D-2-Hydroxyglutaric Aciduria 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.78 SLC25A1 L2HGDH IDH3G IDH3B IDH3A IDH2
2
Show member pathways
13.04 L2HGDH IDH3G IDH3B IDH3A IDH2 FH
3
Show member pathways
11.96 IDH3G IDH3B IDH3A IDH2 IDH1 FH
4
Show member pathways
11.45 IDH3G IDH3B IDH3A IDH2 IDH1 FH
5 11.39 IDH2 IDH1 HIF1A
6
Show member pathways
11.34 L2HGDH IDH3G IDH3B IDH3A IDH2 FH
7
Show member pathways
10.52 IDH2 IDH1

GO Terms for D-2-Hydroxyglutaric Aciduria 1

Cellular components related to D-2-Hydroxyglutaric Aciduria 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.77 SLC25A1 L2HGDH IDH3G IDH3B IDH3A IDH2
2 mitochondrial matrix GO:0005759 9.28 IDH3G IDH3B IDH3A IDH2 GCDH FH

Biological processes related to D-2-Hydroxyglutaric Aciduria 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 10 L2HGDH KDM4C IDH3G IDH3B IDH3A IDH2
2 carbohydrate metabolic process GO:0005975 9.73 IDH3G IDH3A IDH2 GK2
3 tricarboxylic acid cycle GO:0006099 9.63 IDH3G IDH3B IDH3A IDH2 IDH1 FH
4 fatty-acyl-CoA biosynthetic process GO:0046949 9.46 SLC25A1 GCDH
5 fatty acid beta-oxidation using acyl-CoA dehydrogenase GO:0033539 9.4 GCDH ETFA
6 NADP metabolic process GO:0006739 9.37 IDH2 IDH1
7 isocitrate metabolic process GO:0006102 9.35 IDH3G IDH3B IDH3A IDH2 IDH1
8 glyoxylate cycle GO:0006097 9.32 IDH2 IDH1
9 2-oxoglutarate metabolic process GO:0006103 9.1 L2HGDH IDH3B IDH2 IDH1 D2HGDH ADHFE1

Molecular functions related to D-2-Hydroxyglutaric Aciduria 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.81 L2HGDH KDM4C IDH3A IDH2 IDH1 GCDH
2 magnesium ion binding GO:0000287 9.72 IDH3G IDH3B IDH3A IDH2 IDH1
3 flavin adenine dinucleotide binding GO:0050660 9.61 GCDH ETFA D2HGDH
4 isocitrate dehydrogenase (NAD+) activity GO:0004449 9.43 IDH3G IDH3B IDH3A
5 isocitrate dehydrogenase (NADP+) activity GO:0004450 9.4 IDH2 IDH1
6 isocitrate dehydrogenase activity GO:0004448 9.37 IDH2 IDH1
7 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor GO:0016616 9.35 IDH3G IDH3B IDH3A IDH2 IDH1
8 NAD binding GO:0051287 9.02 IDH3G IDH3B IDH3A IDH2 IDH1

Sources for D-2-Hydroxyglutaric Aciduria 1

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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