D2HGDH (D-2-hydroxyglutarate dehydrogenase)

Gene

• Entrez ID: 728294
• Gene name: D-2-hydroxyglutarate dehydrogenase
• Gene symbol: D2HGDH
• Synonyms (NCBI Gene): D2HGD
• Chromosome: 2
• Chromosome location: 2q37.3
• Summary: This gene encodes D-2hydroxyglutarate dehydrogenase, a mitochondrial enzyme belonging to the FAD-binding oxidoreductase/transferase type 4 family. This enzyme, which is most active in liver and kidney but also active in heart and brain, converts D-2-hydro

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121434360	T>C	Pathogenic	Non coding transcript variant, stop lost, 3 prime UTR variant, coding sequence variant, missense variant, genic downstream transcript variant, terminator codon variant
rs121434361	T>G	Pathogenic	Non coding transcript variant, 5 prime UTR variant, coding sequence variant, missense variant
rs121434362	A>G	Pathogenic	Non coding transcript variant, 3 prime UTR variant, missense variant, coding sequence variant, genic downstream transcript variant, synonymous variant
rs145731647	A>G,T	Likely-benign, pathogenic	Intron variant
rs146408017	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant, 5 prime UTR variant, non coding transcript variant
rs146578303	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity, benign	Non coding transcript variant, missense variant, coding sequence variant, genic downstream transcript variant, intron variant
rs147210645	C>A,T	Likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, non coding transcript variant
rs149504235	G>A,C	Likely-benign, conflicting-interpretations-of-pathogenicity, uncertain-significance	Non coding transcript variant, missense variant, coding sequence variant, genic downstream transcript variant, intron variant
rs149628174	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Non coding transcript variant, missense variant, coding sequence variant, genic downstream transcript variant, intron variant
rs267606759	G>A,T	Pathogenic	Non coding transcript variant, intron variant, downstream transcript variant, missense variant, coding sequence variant, 3 prime UTR variant, genic downstream transcript variant
rs369135156	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Downstream transcript variant, genic downstream transcript variant, intron variant
rs587783517	C>T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs749330477	->TC	Pathogenic	Non coding transcript variant, frameshift variant, 5 prime UTR variant, coding sequence variant
rs753528947	A>G	Pathogenic	Splice acceptor variant
rs797045506	T>-	Pathogenic	Coding sequence variant, intron variant, frameshift variant, non coding transcript variant, 3 prime UTR variant, genic downstream transcript variant
rs797045507	T>C	Likely-pathogenic	Genic downstream transcript variant, splice donor variant, intron variant
rs1559361049	T>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1559364994	T>C	Likely-pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT047376	hsa-miR-34a-5p	CLASH	23622248
MIRT922388	hsa-miR-1243	CLIP-seq
MIRT922389	hsa-miR-1273f	CLIP-seq
MIRT922390	hsa-miR-143	CLIP-seq
MIRT922391	hsa-miR-181a	CLIP-seq
MIRT922392	hsa-miR-181b	CLIP-seq
MIRT922393	hsa-miR-181c	CLIP-seq
MIRT922394	hsa-miR-181d	CLIP-seq
MIRT922395	hsa-miR-3654	CLIP-seq
MIRT922396	hsa-miR-3942-3p	CLIP-seq
MIRT922397	hsa-miR-4262	CLIP-seq
MIRT922398	hsa-miR-4313	CLIP-seq
MIRT922399	hsa-miR-433	CLIP-seq
MIRT922400	hsa-miR-4638-3p	CLIP-seq
MIRT922401	hsa-miR-4684-3p	CLIP-seq
MIRT922402	hsa-miR-4708-5p	CLIP-seq
MIRT922403	hsa-miR-4770	CLIP-seq
MIRT922404	hsa-miR-576-3p	CLIP-seq
MIRT1973204	hsa-miR-1234	CLIP-seq
MIRT1973205	hsa-miR-1307	CLIP-seq
MIRT1973206	hsa-miR-136	CLIP-seq
MIRT1973207	hsa-miR-15a	CLIP-seq
MIRT1973208	hsa-miR-15b	CLIP-seq
MIRT1973209	hsa-miR-16	CLIP-seq
MIRT1973210	hsa-miR-195	CLIP-seq
MIRT1973211	hsa-miR-214	CLIP-seq
MIRT1973212	hsa-miR-3173-3p	CLIP-seq
MIRT1973213	hsa-miR-3183	CLIP-seq
MIRT1973214	hsa-miR-361-3p	CLIP-seq
MIRT1973215	hsa-miR-3615	CLIP-seq
MIRT1973216	hsa-miR-3619-5p	CLIP-seq
MIRT1973217	hsa-miR-3677-5p	CLIP-seq
MIRT1973218	hsa-miR-3909	CLIP-seq
MIRT1973219	hsa-miR-424	CLIP-seq
MIRT1973220	hsa-miR-4291	CLIP-seq
MIRT1973221	hsa-miR-4433	CLIP-seq
MIRT1973222	hsa-miR-4638-5p	CLIP-seq
MIRT1973223	hsa-miR-4722-3p	CLIP-seq
MIRT1973224	hsa-miR-4722-5p	CLIP-seq
MIRT1973225	hsa-miR-4723-3p	CLIP-seq
MIRT1973226	hsa-miR-4763-5p	CLIP-seq
MIRT1973227	hsa-miR-4779	CLIP-seq
MIRT1973228	hsa-miR-497	CLIP-seq
MIRT1973229	hsa-miR-550a	CLIP-seq
MIRT1973230	hsa-miR-761	CLIP-seq
MIRT1973231	hsa-miR-885-3p	CLIP-seq
MIRT1973232	hsa-miR-922	CLIP-seq
MIRT1973204	hsa-miR-1234	CLIP-seq
MIRT1973206	hsa-miR-136	CLIP-seq
MIRT2208890	hsa-miR-198	CLIP-seq
MIRT1973211	hsa-miR-214	CLIP-seq
MIRT2208891	hsa-miR-3126-5p	CLIP-seq
MIRT1973216	hsa-miR-3619-5p	CLIP-seq
MIRT2208892	hsa-miR-4419a	CLIP-seq
MIRT2208893	hsa-miR-4510	CLIP-seq
MIRT2208894	hsa-miR-4740-3p	CLIP-seq
MIRT2208895	hsa-miR-544b	CLIP-seq
MIRT1973230	hsa-miR-761	CLIP-seq
MIRT2208896	hsa-miR-941	CLIP-seq
MIRT922404	hsa-miR-576-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003824	Function	Catalytic activity	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	ISS	15070399
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006089	Process	Lactate metabolic process	ISS	15070399
GO:0006103	Process	2-oxoglutarate metabolic process	TAS
GO:0006108	Process	Malate metabolic process	IDA	33431826
GO:0008270	Function	Zinc ion binding	IDA	33431826
GO:0010042	Process	Response to manganese ion	ISS	15070399
GO:0010043	Process	Response to zinc ion	ISS	15070399
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0032025	Process	Response to cobalt ion	ISS	15070399
GO:0032026	Process	Response to magnesium ion	ISS	15070399
GO:0046872	Function	Metal ion binding	IEA
GO:0050660	Function	Flavin adenine dinucleotide binding	IEA
GO:0051592	Process	Response to calcium ion	ISS	15070399
GO:0051990	Function	(R)-2-hydroxyglutarate dehydrogenase activity	EXP	15070399
GO:0051990	Function	(R)-2-hydroxyglutarate dehydrogenase activity	IDA	15070399
GO:0051990	Function	(R)-2-hydroxyglutarate dehydrogenase activity	IEA
GO:0051990	Function	(R)-2-hydroxyglutarate dehydrogenase activity	IMP	20020533, 33431826
GO:0071949	Function	FAD binding	IEA
GO:1901275	Process	Tartrate metabolic process	ISS	15070399

Other IDs

• MIM: 609186
• HGNC: 28358
• e!Ensembl: ENSG00000180902

Protein

• UniProt ID: Q8N465
• Protein name: D-2-hydroxyglutarate dehydrogenase, mitochondrial (EC 1.1.99.39)
• Protein function: Catalyzes the oxidation of D-2-hydroxyglutarate (D-2-HG) to alpha-ketoglutarate (PubMed:15070399, PubMed:15609246, PubMed:16037974, PubMed:20020533, PubMed:33431826). Also catalyzes the oxidation of other D-2-hydroxyacids, such as D-malate (D-MA
• PDB: 6LPN, 6LPP, 6LPQ, 6LPT, 6LPU, 6LPX
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01565	FAD_binding_4	100 → 239	FAD binding domain	Domain
  PF02913	FAD-oxidase_C	275 → 516	FAD linked oxidases, C-terminal domain	Domain

• Sequence:

  MLPRRPLAWPAWLLRGAPGAAGSWGRPVGPLARRGCCSAPGTPEVPLTRERYPVRRLPFS
  TVSKQDLAAFERIVPGGVVTDPEALQAPNVDWLRTLRGCSKVLLRPRTSEEVSHILRHCH
  ERNLAVNPQGGNTGMVGGSVPVFDEIILSTARMNRVLSFHSVSGILVCQAGCVLEELSRY
  VEERDFIMPLDLGAKGSCHIGGNVATNAGGLRFLRYGSLHGTVLGLEVVLADGTVLDCLT
  SLRKDNTGYDLKQLFIGSEGTLGIITTVSILCPPKPRAVNVAFLGCPGFAEVLQTFSTCK
  GMLGEILSAFEFMDAVCMQLVGRHLHLASPVQESPFYVLIETSGSNAGHDAEKLGHFLEH
  ALGSGLVTDGTMATDQRKVKMLWALRERITEALSRDGYVYKYDLSLPVERLYDIVTDLRA
  RLGPHAKHVVGYGHLGDGNLHLNVTAEAFSPSLLAALEPHVYEWTAGQQGSVSAEHGVGF
  RKRDVLGYSKPPGALQLMQQLKALLDPKGILNPYKTLPSQA

• Sequence length: 521

Pathways

Reactome:

Interconversion of 2-oxoglutarate and 2-hydroxyglutarate

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
D-2-hydroxyglutaric aciduria	Pathogenic; Likely pathogenic	rs797045506, rs797045507	RCV000192342 RCV000192863	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
D-2-hydroxyglutaric aciduria 1	Pathogenic; Likely pathogenic	rs1699275754, rs2125158367, rs121434360, rs121434361, rs145731647, rs753528947, rs121434362, rs749330477, rs142050154, rs1692452859, rs1158737546, rs2549948325, rs1692428076, rs1559364994, rs1559361049, rs1559404382	RCV001322380 RCV001988194 RCV000001926 RCV000001927 RCV000001928 RCV000001929 RCV000001930 RCV000001931 RCV005095992 RCV002471951 RCV002715131 RCV002829837 RCV003990934 RCV000691213 RCV000694373 RCV000703265	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AMINO ACID METABOLISM, INBORN ERRORS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATOPIC ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATOPIC ECZEMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHILDHOOD ONSET ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED D-2-HYDROXYGLUTARIC ACIDURIA AND L-2-HYDROXYGLUTARIC ACIDURIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
D2HGDH-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASE	—	CTD, ClinGen	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RESPIRATORY SYSTEM DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEASONAL ALLERGIC RHINITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adult Diffuse Large B-Cell Lymphoma	B-cell Lymphoma	BEFREE	26178471		★☆☆☆☆ Found in Text Mining only
Amino Acid Metabolism, Inborn Errors	Disorder of amino acid metabolism	CTD_human_DG	15609246		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Amino Acid Metabolism, Inherited Disorders	Inherited Errors of Amino Acid Metabolism	CTD_human_DG	15609246		★☆☆☆☆ Found in Text Mining only
Aortic Valve Insufficiency	Aortic Valve Insufficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	GWASCAT_DG	27182965, 29785011, 30552067, 30929738, 31036433, 31619474		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinoma Ovarian Epithelial	Epithelial ovarian carcinoma	Pubtator	33173439	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Childhood asthma	Asthma	GWASCAT_DG	30929738, 31036433		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	29339485		★☆☆☆☆ Found in Text Mining only
Diffuse Large B-Cell Lymphoma	Diffuse Lymphoma	BEFREE	26178471		★☆☆☆☆ Found in Text Mining only
Eczema	Eczema	GWASCAT_DG	30595370		★☆☆☆☆ Found in Text Mining only
Frontal bossing	Frontal bossing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	21625441		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	32386320, 36541697	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	33284559	Associate	★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	26178471, 29339485		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	29339485		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	16081310, 6774165		★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	Pubtator	38169377	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	BEFREE	19169842		★☆☆☆☆ Found in Text Mining only
Peripheral Neuropathy	Peripheral Neuropathy	BEFREE	19169842		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	27322736	Associate	★☆☆☆☆ Found in Text Mining only
Respiratory Tract Diseases	Respiratory Tract Diseases	GWASCAT_DG	30595370		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	31927533	Associate	★☆☆☆☆ Found in Text Mining only
Tonic - clonic seizures	Seizure	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	29339485		★☆☆☆☆ Found in Text Mining only