D2HGA1
MCID: D2H002
MIFTS: 52

D-2-Hydroxyglutaric Aciduria 1 (D2HGA1)

Categories: Cardiovascular diseases, Eye diseases, Genetic diseases, Mental diseases, Metabolic diseases, Nephrological 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 56 12 73 29 6 71
D-2-Hydroxyglutaric Aciduria 56 12 52 58 36 29 13 6 15 39 71
D2hga1 56 12 73
D-2-Hydroxyglutaric Acidemia 52 58
D-2-Hga 52 58
D2ha 52 73
Combined D-2- and L-2-Hydroxyglutaric Aciduria 71
Aciduria, D-2-Hydroxyglutaric, Type 1 39
D2hga 56

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:

56
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 56 600721
OMIM Phenotypic Series 56 PS600721
KEGG 36 H01225
MeSH 43 D020739
ICD10 via Orphanet 33 E72.8
Orphanet 58 ORPHA79315
UMLS 71 C1833429 C2746066 C3152055

Summaries for D-2-Hydroxyglutaric Aciduria 1

NIH Rare Diseases : 52 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 brain, cortex and skeletal muscle, and related phenotypes are intellectual disability and global developmental delay

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 : 56 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)

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 76)
# Related Disease Score Top Affiliating Genes
1 d-2-hydroxyglutaric aciduria 2 34.4 L2HGDH IDH3G IDH2 D2HGDH ADHFE1
2 combined d-2- and l-2-hydroxyglutaric aciduria 32.8 SLC25A1 L2HGDH KDM4C IDH2 D2HGDH ADHFE1
3 2-hydroxyglutaric aciduria 30.3 SLC25A1 L2HGDH KDM4C IDH3G IDH3B IDH3A
4 l-2-hydroxyglutaric aciduria 29.5 SLC25A1 L2HGDH KDM4C IDH2 IDH1 G6PC3
5 metaphyseal enchondromatosis with d-2-hydroxyglutaric aciduria 12.7
6 hypotonia 10.7
7 organic acidemia 10.5
8 enchondroma 10.5 IDH2 IDH1
9 yemenite deaf-blind hypopigmentation syndrome 10.5
10 cortical blindness 10.5
11 breast intraductal papillomatosis 10.5 IDH2 IDH1
12 intraductal papilloma 10.5 IDH2 IDH1
13 breast duct papilloma 10.5 IDH2 IDH1
14 breast papillomatosis 10.4 IDH2 IDH1
15 adult brain stem glioma 10.4 IDH2 IDH1
16 cytogenetically normal acute myeloid leukemia 10.4 IDH2 IDH1
17 periosteal chondrosarcoma 10.4 IDH2 IDH1
18 breast hemangioma 10.4 IDH2 IDH1
19 adult oligodendroglioma 10.4 IDH2 IDH1
20 encephalopathy 10.4
21 childhood oligodendroglioma 10.4 IDH2 IDH1
22 interval angle-closure glaucoma 10.4 IDH2 IDH1
23 inhibited female orgasm 10.4 IDH3G IDH3A
24 gemistocytic astrocytoma 10.4 IDH2 IDH1
25 adult astrocytic tumour 10.3 IDH2 IDH1
26 chondroblastic osteosarcoma 10.3 IDH2 IDH1
27 atrial standstill 1 10.3
28 visual epilepsy 10.3
29 inherited metabolic disorder 10.3
30 seizure disorder 10.3
31 intraductal breast benign neoplasm 10.3 IDH2 IDH1
32 fibrillary astrocytoma 10.3 KDM4C IDH2 IDH1
33 intracranial chondrosarcoma 10.3 IDH2 IDH1 ADHFE1
34 mixed oligodendroglioma-astrocytoma 10.3 IDH2 IDH1
35 brain stem glioma 10.3 KDM4C IDH2 IDH1
36 brain glioma 10.3 KDM4C IDH2 IDH1
37 mixed glioma 10.3 IDH2 IDH1
38 bile duct adenocarcinoma 10.2 KDM4C IDH2 IDH1
39 bone sarcoma 10.2 KDM4C IDH2 IDH1
40 grade iii astrocytoma 10.2 KDM4C IDH2 IDH1
41 spindle cell hemangioma 10.2 IDH2 IDH1
42 hydrocephalus, congenital, 1 10.2
43 leukemia, acute myeloid 10.2
44 autosomal recessive disease 10.2
45 pyloric stenosis 10.2
46 mucopolysaccharidosis iii 10.2
47 dilated cardiomyopathy 10.2
48 hemangioma 10.2
49 myopathy 10.2
50 egg allergy 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 intellectual disability 31 HP:0001249
2 global developmental delay 31 HP:0001263
3 muscular hypotonia 31 HP:0001252
4 macrocephaly 31 HP:0000256
5 muscle weakness 31 HP:0001324
6 prominent forehead 31 HP:0011220
7 frontal bossing 31 HP:0002007
8 micrognathia 31 HP:0000347
9 apnea 31 HP:0002104
10 cardiomyopathy 31 HP:0001638
11 aortic regurgitation 31 HP:0001659
12 generalized hypotonia 31 HP:0001290
13 multifocal cerebral white matter abnormalities 31 HP:0007052
14 episodic vomiting 31 HP:0002572
15 inspiratory stridor 31 HP:0005348
16 delayed cns myelination 31 HP:0002188
17 dilation of lateral ventricles 31 HP:0006956
18 subependymal cysts 31 HP:0002416
19 infantile encephalopathy 31 HP:0007105
20 glutaric aciduria 31 HP:0003150
21 seizure 31 HP:0001250
22 d-2-hydroxyglutaric aciduria 31 HP:0012321

Symptoms via clinical synopsis from OMIM:

56
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

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
Brain, 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 71)
# Title Authors PMID Year
1
Mutations in phenotypically mild D-2-hydroxyglutaric aciduria. 6 56 61
16037974 2005
2
Phenotypic heterogeneity in the presentation of D-2-hydroxyglutaric aciduria in monozygotic twins. 61 6 56
16081310 2005
3
Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. 61 56 6
15609246 2005
4
D-2-hydroxyglutaric aciduria in a newborn with neurological abnormalities: a new neurometabolic disorder? 56 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. 56 61
20020533 2010
7
D-2-hydroxyglutaric aciduria: a case with an intermediate phenotype and prenatal diagnosis of two affected fetuses. 56 61
12884432 2003
8
Spondyloenchondromatosis with D-2-hydroxyglutaric aciduria: a report of a second patient with this unusual combination. 56 61
12868470 2003
9
D-2-hydroxyglutaric aciduria in association with spondyloenchondromatosis. 56 61
10883451 2000
10
Facial anomalies in D-2-hydroxyglutaric aciduria. 56 61
10449646 1999
11
D-2-hydroxyglutaric aciduria: further clinical delineation. 61 56
10407777 1999
12
D-2-hydroxyglutaric aciduria. 61 56
7782605 1995
13
D-2-hydroxyglutaric aciduria: case report and biochemical studies. 56 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. 56
15602086 2005
17
IDH1 mutated acute myeloid leukemia in a child with metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria. 61
32166993 2020
18
Inborn errors of metabolite repair. 61
31691304 2020
19
D-2-Hydroxyglutaric Aciduria with Enchondromatosis and Angiokeratoma Circumscriptum. 61
31890366 2019
20
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
21
D-2-hydroxyglutaric aciduria in a patient with speech delay due to a novel homozygous deletion in the D2HGDH gene. 61
31431883 2019
22
D-2-hydroxyglutaric aciduria Type I: Functional analysis of D2HGDH missense variants. 61
30908763 2019
23
Widespread and debilitating hemangiomas in a patient with enchondromatosis and D-2-hydroxyglutaric aciduria. 61
29744569 2018
24
Computational approach to unravel the impact of missense mutations of proteins (D2HGDH and IDH2) causing D-2-hydroxyglutaric aciduria 2. 61
29987523 2018
25
A small molecule inhibitor of mutant IDH2 rescues cardiomyopathy in a D-2-hydroxyglutaric aciduria type II mouse model. 61
27469509 2016
26
The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in oncogenesis and survival prolongation. 61
24880135 2014
27
Disruption of redox homeostasis and histopathological alterations caused by in vivo intrastriatal administration of D-2-hydroxyglutaric acid to young rats. 61
25043325 2014
28
Child Neurology: cognitive delay in a 7-year-old girl. 61
24218321 2013
29
Metaphyseal chondromatosis combined with D-2-hydroxyglutaric aciduria in four patients. 61
22639207 2012
30
IDH1 and IDH2 have critical roles in 2-hydroxyglutarate production in D-2-hydroxyglutarate dehydrogenase depleted cells. 61
22683334 2012
31
Progress in understanding 2-hydroxyglutaric acidurias. 61
22391998 2012
32
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
33
Whole-exome sequencing detects somatic mutations of IDH1 in metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA). 61
22025298 2011
34
Co-morbidity of Sanfilippo syndrome type C and D-2-hydroxyglutaric aciduria. 61
21384162 2011
35
Metabolic syndromes and malignant transformation: where the twain shall meet. 61
20962328 2010
36
IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. 61
20847235 2010
37
Peripheral neuropathy in a patient with D-2-hydroxyglutaric aciduria. 61
19169842 2009
38
[D-2-hydroxyglutaric aciduria. Report of two cases]. 61
19961059 2009
39
Measurement of D: -2-hydroxyglutarate dehydrogenase activity in cell homogenates derived from D: -2-hydroxyglutaric aciduria patients. 61
19283509 2009
40
D-2-hydroxyglutaric aciduria in three patients with proven SSADH deficiency: genetic coincidence or a related biochemical epiphenomenon? 61
16442322 2006
41
D-2-Hydroxyglutaric aciduria: unravelling the biochemical pathway and the genetic defect. 61
16601864 2006
42
Mitochondrial energy metabolism is markedly impaired by D-2-hydroxyglutaric acid in rat tissues. 61
15963747 2005
43
Kinetic characterization of human hydroxyacid-oxoacid transhydrogenase: relevance to D-2-hydroxyglutaric and gamma-hydroxybutyric acidurias. 61
16435184 2005
44
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
45
D-2-hydroxyglutaric aciduria and glutaric aciduria type 1 in siblings: coincidence, or linked disorders? 61
15248096 2004
46
In vitro effects of D-2-hydroxyglutaric acid on glutamate binding, uptake and release in cerebral cortex of rats. 61
14706223 2004
47
Inhibition of creatine kinase activity from rat cerebral cortex by D-2-hydroxyglutaric acid in vitro. 61
12963087 2004
48
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
49
D-2-hydroxyglutaric acid inhibits creatine kinase activity from cardiac and skeletal muscle of young rats. 61
14511354 2003
50
Inhibition of mitochondrial creatine kinase activity by D-2-hydroxyglutaric acid in cerebellum of young rats. 61
12938854 2003

Variations for D-2-Hydroxyglutaric Aciduria 1

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

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 D2HGDH NM_152783.5(D2HGDH):c.642del (p.Arg215fs)deletion Pathogenic 572875 rs1559361049 2:242683187-242683187 2:241743772-241743772
2 D2HGDH NC_000002.12:g.(?_241741010)_(241767989_?)deldeletion Pathogenic 539292 2:242680425-242707404 2:241741010-241767989
3 D2HGDH NM_152783.5(D2HGDH):c.1331T>C (p.Val444Ala)SNV Pathogenic 1852 rs121434360 2:242707149-242707149 2:241767734-241767734
4 D2HGDH NM_152783.5(D2HGDH):c.440T>G (p.Ile147Ser)SNV Pathogenic 1853 rs121434361 2:242681939-242681939 2:241742524-241742524
5 D2HGDH NM_152783.5(D2HGDH):c.293-23A>GSNV Pathogenic 1854 rs145731647 2:242680425-242680425 2:241741010-241741010
6 D2HGDH NM_152783.5(D2HGDH):c.685-2A>GSNV Pathogenic 1855 rs753528947 2:242684122-242684122 2:241744707-241744707
7 D2HGDH NM_152783.5(D2HGDH):c.1315A>G (p.Asn439Asp)SNV Pathogenic 1856 rs121434362 2:242707133-242707133 2:241767718-241767718
8 D2HGDH NM_152783.5(D2HGDH):c.325_326dup (p.Glu110fs)duplication Pathogenic 1857 rs749330477 2:242680479-242680480 2:241741064-241741065
9 D2HGDH NM_152783.5(D2HGDH):c.1123G>T (p.Asp375Tyr)SNV Pathogenic 1858 rs267606759 2:242690786-242690786 2:241751371-241751371
10 D2HGDH NM_152783.5(D2HGDH):c.566C>T (p.Pro189Leu)SNV Pathogenic 158422 rs587783517 2:242683112-242683112 2:241743697-241743697
11 D2HGDH NM_152783.5(D2HGDH):c.1027del (p.Ser343fs)deletion Pathogenic 210809 rs797045506 2:242690689-242690689 2:241751274-241751274
12 D2HGDH NM_152783.5(D2HGDH):c.1306+2T>CSNV Likely pathogenic 210815 rs797045507 2:242695431-242695431 2:241756016-241756016
13 D2HGDH NM_152783.5(D2HGDH):c.853+2T>CSNV Likely pathogenic 570363 rs1559364994 2:242684294-242684294 2:241744879-241744879
14 D2HGDH NM_152783.5(D2HGDH):c.517G>A (p.Val173Ile)SNV Conflicting interpretations of pathogenicity 432634 rs146408017 2:242683063-242683063 2:241743648-241743648
15 D2HGDH NM_152783.5(D2HGDH):c.720C>A (p.Thr240=)SNV Conflicting interpretations of pathogenicity 434886 rs147210645 2:242684159-242684159 2:241744744-241744744
16 D2HGDH NM_152783.5(D2HGDH):c.1515G>A (p.Leu505=)SNV Conflicting interpretations of pathogenicity 780102 2:242707333-242707333 2:241767918-241767918
17 D2HGDH NM_152783.5(D2HGDH):c.854-8C>TSNV Conflicting interpretations of pathogenicity 733943 2:242689558-242689558 2:241750143-241750143
18 D2HGDH NM_152783.5(D2HGDH):c.963C>T (p.Val321=)SNV Conflicting interpretations of pathogenicity 737190 2:242689675-242689675 2:241750260-241750260
19 D2HGDH NM_152783.5(D2HGDH):c.1446G>A (p.Lys482=)SNV Conflicting interpretations of pathogenicity 746005 2:242707264-242707264 2:241767849-241767849
20 D2HGDH NM_152783.5(D2HGDH):c.854-7G>ASNV Conflicting interpretations of pathogenicity 755536 2:242689559-242689559 2:241750144-241750144
21 D2HGDH NM_152783.5(D2HGDH):c.-92-4C>GSNV Conflicting interpretations of pathogenicity 218849 rs146482048 2:242674544-242674544 2:241735129-241735129
22 D2HGDH NM_152783.5(D2HGDH):c.423C>T (p.Pro141=)SNV Conflicting interpretations of pathogenicity 158419 rs142473303 2:242681922-242681922 2:241742507-241742507
23 D2HGDH NM_152783.5(D2HGDH):c.1258G>A (p.Ala420Thr)SNV Conflicting interpretations of pathogenicity 158409 rs149504235 2:242695381-242695381 2:241755966-241755966
24 D2HGDH NM_152783.5(D2HGDH):c.1276G>A (p.Ala426Thr)SNV Conflicting interpretations of pathogenicity 158410 rs146578303 2:242695399-242695399 2:241755984-241755984
25 D2HGDH NM_152783.5(D2HGDH):c.1140+8G>ASNV Conflicting interpretations of pathogenicity 210813 rs369135156 2:242690811-242690811 2:241751396-241751396
26 D2HGDH NM_152783.5(D2HGDH):c.1272G>A (p.Pro424=)SNV Conflicting interpretations of pathogenicity 210814 rs375565047 2:242695395-242695395 2:241755980-241755980
27 D2HGDH NM_152783.5(D2HGDH):c.1183C>T (p.Arg395Trp)SNV Conflicting interpretations of pathogenicity 335317 rs149628174 2:242695306-242695306 2:241755891-241755891
28 D2HGDH NM_152783.5(D2HGDH):c.893C>T (p.Thr298Ile)SNV Conflicting interpretations of pathogenicity 335315 rs141475702 2:242689605-242689605 2:241750190-241750190
29 GJB1 NM_000166.6(GJB1):c.425G>A (p.Arg142Gln)SNV Conflicting interpretations of pathogenicity 188174 rs786204123 X:70443982-70443982 X:71224132-71224132
30 D2HGDH NM_152783.5(D2HGDH):c.540T>C (p.Tyr180=)SNV Uncertain significance 335313 rs752626142 2:242683086-242683086 2:241743671-241743671
31 D2HGDH NM_152783.5(D2HGDH):c.*499G>ASNV Uncertain significance 335340 rs886055851 2:242707883-242707883 2:241768468-241768468
32 D2HGDH NM_152783.5(D2HGDH):c.*597C>TSNV Uncertain significance 335343 rs187157907 2:242707981-242707981 2:241768566-241768566
33 D2HGDH NM_152783.5(D2HGDH):c.*680G>CSNV Uncertain significance 335346 rs749772854 2:242708064-242708064 2:241768649-241768649
34 D2HGDH NM_152783.5(D2HGDH):c.1357C>T (p.Leu453Phe)SNV Uncertain significance 335319 rs145839736 2:242707175-242707175 2:241767760-241767760
35 D2HGDH NM_152783.5(D2HGDH):c.1502T>C (p.Leu501Pro)SNV Uncertain significance 335322 rs747738269 2:242707320-242707320 2:241767905-241767905
36 D2HGDH NM_152783.5(D2HGDH):c.*411dupduplication Uncertain significance 335335 rs113265004 2:242707789-242707790 2:241768374-241768375
37 D2HGDH NM_152783.5(D2HGDH):c.*503C>TSNV Uncertain significance 335341 rs755235230 2:242707887-242707887 2:241768472-241768472
38 D2HGDH NM_152783.5(D2HGDH):c.-141C>TSNV Uncertain significance 335305 rs886055845 2:242674062-242674062 2:241734647-241734647
39 D2HGDH NM_152783.5(D2HGDH):c.923C>G (p.Ser308Cys)SNV Uncertain significance 335316 rs886055848 2:242689635-242689635 2:241750220-241750220
40 D2HGDH NM_152783.5(D2HGDH):c.1199A>G (p.Tyr400Cys)SNV Uncertain significance 335318 rs138598929 2:242695322-242695322 2:241755907-241755907
41 D2HGDH NM_152783.5(D2HGDH):c.1453G>A (p.Val485Ile)SNV Uncertain significance 335320 rs375162898 2:242707271-242707271 2:241767856-241767856
42 D2HGDH NM_152783.5(D2HGDH):c.1523A>G (p.Lys508Arg)SNV Uncertain significance 335324 rs770361030 2:242707341-242707341 2:241767926-241767926
43 D2HGDH NM_152783.5(D2HGDH):c.1547C>T (p.Thr516Met)SNV Uncertain significance 335325 rs762019434 2:242707365-242707365 2:241767950-241767950
44 D2HGDH NM_152783.5(D2HGDH):c.1505A>G (p.Lys502Arg)SNV Uncertain significance 335323 rs751788334 2:242707323-242707323 2:241767908-241767908
45 D2HGDH NM_152783.5(D2HGDH):c.*171G>ASNV Uncertain significance 335330 rs886055849 2:242707555-242707555 2:241768140-241768140
46 D2HGDH NM_152783.5(D2HGDH):c.*194G>ASNV Uncertain significance 335331 rs537045408 2:242707578-242707578 2:241768163-241768163
47 D2HGDH NM_152783.5(D2HGDH):c.424G>A (p.Val142Ile)SNV Uncertain significance 335311 rs143231454 2:242681923-242681923 2:241742508-241742508
48 D2HGDH NM_152783.5(D2HGDH):c.567G>A (p.Pro189=)SNV Uncertain significance 335314 rs140447217 2:242683113-242683113 2:241743698-241743698
49 D2HGDH NM_152783.5(D2HGDH):c.*717C>GSNV Uncertain significance 335348 rs555898820 2:242708101-242708101 2:241768686-241768686
50 D2HGDH NM_152783.5(D2HGDH):c.*87C>TSNV Uncertain significance 335328 rs546752536 2:242707471-242707471 2:241768056-241768056

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 9.71 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 9.43 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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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