OGDH

Summary

OGDH (oxoglutarate dehydrogenase, HGNC:8124) is a protein-coding gene on chromosome 7p13, encoding 2-oxoglutarate dehydrogenase complex component E1 (Q02218). 2-oxoglutarate dehydrogenase (E1o) component of the 2-oxoglutarate dehydrogenase complex (OGDHC). It is a selective cancer dependency (DepMap: 43.6% of cell lines).

This gene encodes one subunit of the 2-oxoglutarate dehydrogenase complex. This complex catalyzes the overall conversion of 2-oxoglutarate (alpha-ketoglutarate) to succinyl-CoA and CO(2) during the Krebs cycle. The protein is located in the mitochondrial matrix and uses thiamine pyrophosphate as a cofactor. A congenital deficiency in 2-oxoglutarate dehydrogenase activity is believed to lead to hypotonia, metabolic acidosis, and hyperlactatemia. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 4967 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 278 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 29
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 43.6% of screened cell lines
• MANE Select transcript: NM_002541

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8124
Approved symbol	OGDH
Name	oxoglutarate dehydrogenase
Location	7p13
Locus type	gene with protein product
Status	Approved
Aliases	E1k, OGDC-E1, OGDH2, KGD1
Ensembl gene	ENSG00000105953
Ensembl biotype	protein_coding
OMIM	613022
Entrez	4967

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 54 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000222673, ENST00000419661, ENST00000439616, ENST00000443864, ENST00000444676, ENST00000447398, ENST00000449767, ENST00000459672, ENST00000497326, ENST00000906369, ENST00000906370, ENST00000906371, ENST00000906372, ENST00000906373, ENST00000906374, ENST00000906375, ENST00000906376, ENST00000906377, ENST00000906378, ENST00000906379, ENST00000906380, ENST00000906381, ENST00000906382, ENST00000906383, ENST00000906384, ENST00000906385, ENST00000906386, ENST00000906387, ENST00000906388, ENST00000906389, ENST00000906390, ENST00000906391, ENST00000906392, ENST00000906393, ENST00000906394, ENST00000906395, ENST00000906396, ENST00000906397, ENST00000906398, ENST00000906399, ENST00000906400, ENST00000906401, ENST00000906402, ENST00000930776, ENST00000930777, ENST00000930778, ENST00000930779, ENST00000930780, ENST00000930781, ENST00000962342, ENST00000962343, ENST00000962344, ENST00000962345, ENST00000962346, ENST00000962347, ENST00000962348

RefSeq mRNA: 4 — MANE Select: NM_002541 NM_001003941, NM_001165036, NM_001363523, NM_002541

CCDS: CCDS34627, CCDS47580, CCDS55107, CCDS87498

Canonical transcript exons

ENST00000222673 — 23 exons

Exon	Start	End
ENSE00000681481	44645327	44645518
ENSE00000681515	44675178	44675268
ENSE00000681522	44675970	44676149
ENSE00000681542	44694424	44694576
ENSE00000681548	44696025	44696127
ENSE00000681555	44696429	44696557
ENSE00000681560	44696914	44697064
ENSE00000681566	44697370	44697497
ENSE00001192073	44624317	44624565
ENSE00001648025	44700141	44700269
ENSE00001668217	44693825	44694004
ENSE00001679409	44707879	44709066
ENSE00001680954	44681720	44681848
ENSE00001708467	44701543	44701615
ENSE00001721265	44698192	44698263
ENSE00001745088	44707225	44707388
ENSE00001753231	44647657	44647759
ENSE00001802577	44707582	44707736
ENSE00001849972	44606627	44606653
ENSE00002190027	44697604	44697782
ENSE00003464721	44674411	44674557
ENSE00003617923	44673787	44673941
ENSE00003790214	44666736	44666851

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.2581 / max 263.1644, expressed in 1816 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78420	15.0355	1804
78419	11.3513	1781
78418	3.5376	1592
78425	0.2658	38
78426	0.0680	21

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.90	gold quality
gastrocnemius	UBERON:0001388	98.60	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.47	gold quality
heart left ventricle	UBERON:0002084	98.32	gold quality
cardiac ventricle	UBERON:0002082	98.26	gold quality
muscle of leg	UBERON:0001383	98.07	gold quality
right atrium auricular region	UBERON:0006631	97.81	gold quality
cardiac atrium	UBERON:0002081	97.45	gold quality
heart	UBERON:0000948	97.15	gold quality
muscle organ	UBERON:0001630	96.84	gold quality
skeletal muscle organ	UBERON:0014892	96.84	gold quality
triceps brachii	UBERON:0001509	96.68	gold quality
left ventricle myocardium	UBERON:0006566	96.61	gold quality
gluteal muscle	UBERON:0002000	96.43	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.98	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.76	gold quality
lower esophagus	UBERON:0013473	95.75	gold quality
right adrenal gland	UBERON:0001233	95.72	gold quality
right adrenal gland cortex	UBERON:0035827	95.58	gold quality
adult mammalian kidney	UBERON:0000082	95.49	gold quality
left adrenal gland	UBERON:0001234	95.46	gold quality
left adrenal gland cortex	UBERON:0035825	95.33	gold quality
heart right ventricle	UBERON:0002080	95.18	gold quality
body of tongue	UBERON:0011876	95.18	gold quality
right lobe of thyroid gland	UBERON:0001119	95.13	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.05	gold quality
transverse colon	UBERON:0001157	94.98	gold quality
metanephros cortex	UBERON:0010533	94.94	gold quality
skeletal muscle tissue	UBERON:0001134	94.91	gold quality
adrenal cortex	UBERON:0001235	94.91	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A

miRNA regulators (miRDB)

4 targeting OGDH, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-619-5P	98.57	64.97	1988

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 43.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• 2-oxoglutarate (alpha-ketoglutarate) dehydrogenase stability is regulated by the RING finger ubiquitin ligase Siah (PMID:15466852)
• Reduction in the E2k subunit of the alpha-ketoglutarate dehydrogenase complex has effects independent of complex activity. (PMID:15649899)
• Association with autosomal recessive DOOR syndrome not found. (PMID:17343268)
• Differences in oxoglutarate dehydrogenase activity suggest that there is no excess mitochondrial capacity during maximal exercise with a small muscle mass. (PMID:21611730)
• Acute inhibition of alpha-ketoglutarate dehydrogenase produces effects on calcium opposite to those in Alzheimer’s disease (AD), while the chronic or long-term inhibition of alpha-KGDHC mimicked the AD-related changes in calcium. (PMID:22169199)
• ATP consumption is demonstrated in respiration-impaired isolated mice and in situ neuronal mitochondria from transgenic mice with dihydrolipoyl succinyltransferase deficiency. (PMID:23475850)
• Tissue-specific expression of OGDH splice variants may thus provide a mechanism that tunes the control of the enzyme to the specialized metabolic and signalling needs of individual cell types (PMID:26936970)
• The data indicate that amino acid/nucleotide metabolism-related genes OGDH, PPAT and PCCA acquire somatic mutations in microsatellite instability-high gastric cancers and colorectal cancers and that mutational intratumoral heterogeneity may occur in at least some of these tumors. (PMID:27468871)
• oxoglutarate dehydrogenase (OGDH) and lipoic acid synthase (LIAS), which when mutated stabilize HIF1alpha in a non-hydroxylated form. (PMID:27923773)
• PIK3CA mutant cancer cells require PIK3CA but also require the expression of the TCA cycle enzyme 2-oxoglutarate dehydrogenase (OGDH). (PMID:28396387)
• there is the direct interaction between SIRT5 and 2-oxoglutarate dehydrogenase (OGDH), and desuccinylation of OGDH by SIRT5 inhibits the activity of OGDH complex. (PMID:31247190)
• Synthetic analogues of 2-oxo acids discriminate metabolic contribution of the 2-oxoglutarate and 2-oxoadipate dehydrogenases in mammalian cells and tissues. (PMID:32024885)
• DHTKD1 and OGDH display substrate overlap in cultured cells and form a hybrid 2-oxo acid dehydrogenase complex in vivo. (PMID:32160276)
• A biallelic pathogenic variant in the OGDH gene results in a neurological disorder with features of a mitochondrial disease. (PMID:32383294)
• Biallelic variants in OGDH encoding oxoglutarate dehydrogenase lead to a neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities. (PMID:36520152)
• OGDH and Bcl-xL loss causes synthetic lethality in glioblastoma. (PMID:38483541)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ogdha	ENSDARG00000034270
danio_rerio	ogdhb	ENSDARG00000103428
mus_musculus	Ogdh	ENSMUSG00000020456
rattus_norvegicus	Ogdh	ENSRNOG00000005130
drosophila_melanogaster	Ogdh	FBGN0010352
drosophila_melanogaster	CG33791	FBGN0035240
caenorhabditis_elegans		WBGENE00020679

Paralogs (2): DHTKD1 (ENSG00000181192), OGDHL (ENSG00000197444)

Protein

Protein identifiers

2-oxoglutarate dehydrogenase complex component E1 — Q02218 (reviewed: Q02218)

Alternative names: 2-oxoglutarate dehydrogenase, mitochondrial, Alpha-ketoglutarate dehydrogenase, Thiamine diphosphate (ThDP)-dependent 2-oxoglutarate dehydrogenase

All UniProt accessions (6): Q02218, A0A140VJQ5, C9J4G7, E9PCR7, E9PDF2, E9PFG7

UniProt curated annotations — full annotation on UniProt →

Function. 2-oxoglutarate dehydrogenase (E1o) component of the 2-oxoglutarate dehydrogenase complex (OGDHC). Participates in the first step, rate limiting for the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) catalyzed by the whole OGDHC. Catalyzes the irreversible decarboxylation of 2-oxoglutarate (alpha-ketoglutarate) via the thiamine diphosphate (ThDP) cofactor and subsequent transfer of the decarboxylated acyl intermediate on an oxidized dihydrolipoyl group that is covalently amidated to the E2 enzyme (dihydrolipoyllysine-residue succinyltransferase or DLST). Plays a key role in the Krebs (citric acid) cycle, which is a common pathway for oxidation of fuel molecules, including carbohydrates, fatty acids, and amino acids. Can catalyze the decarboxylation of 2-oxoadipate in vitro, but at a much lower rate than 2-oxoglutarate. Can also convert 2-keto-4-hydroxyglutarate (KHG) and CoA into malyl-CoA. Mainly active in the mitochondrion. A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A.

Subunit / interactions. Homodimer. The 2-oxoglutarate dehydrogenase complex is composed of OGDH (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide succinyltransferase; E2), DLD (dihydrolipoamide dehydrogenase; E3), and the assembly factor KGD4. It contains multiple copies of the three enzymatic components (E1, E2 and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex associates with KAT2A. Interacts with ABHD11; this interaction maintains the functional lipoylation of the 2-oxoglutarate dehydrogenase complex.

Subcellular location. Mitochondrion. Nucleus.

Activity regulation. Calcium ions and ADP stimulate, whereas ATP and NADH reduce catalytic activity.

Miscellaneous. Probably insensitive to calcium. The mitochondrial 2-oxoglutarate and 2-oxoadipate dehydrogenase complexes (OGDHC and OADHC, respectively) share their E2 (DLST) and E3 (dihydrolipoyl dehydrogenase or DLD) components, but the E1 component is specific to each complex (E1o and E1a (DHTK1), respectively).

Similarity. Belongs to the alpha-ketoglutarate dehydrogenase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q02218-1	1	yes
Q02218-2	2
Q02218-3	3

RefSeq proteins (4): NP_001003941, NP_001158508, NP_001350452, NP_002532* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001017	DH_E1	Domain
IPR005475	Transketolase-like_Pyr-bd	Domain
IPR011603	2oxoglutarate_DH_E1	Family
IPR029061	THDP-binding	Homologous_superfamily
IPR031717	ODO-1/KGD_C	Domain
IPR032106	2-oxogl_dehyd_N	Domain
IPR042179	KGD_C_sf	Homologous_superfamily

Pfam: PF00676, PF02779, PF16078, PF16870

Enzyme classification (BRENDA):

• EC 1.2.1.105 — 2-oxoglutarate dehydrogenase system (BRENDA: 28 organisms, 44 substrates, 119 inhibitors, 83 Km, 16 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2-OXOGLUTARATE	0.0025–10.1	50
COA	0.0032–0.075	11
NAD+	0.0249–0.3	11
2-OXOVALERATE	0.0063–0.0163	5
2-OXOADIPATE	0.107–0.52	2

Catalyzed reactions (Rhea), 1 shown:

• N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 2-oxoglutarate + H(+) = N(6)-[(R)-S(8)-succinyldihydrolipoyl]-L-lysyl-[protein] + CO2 (RHEA:12188)

UniProt features (116 total): helix 40, strand 40, binding site 11, turn 7, modified residue 5, sequence conflict 4, splice variant 3, mutagenesis site 2, transit peptide 1, chain 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3ERY	X-RAY DIFFRACTION	1.95
8I0K	ELECTRON MICROSCOPY	2.86
7WGR	ELECTRON MICROSCOPY	2.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02218-F1	90.73	0.82

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (11): 446; 446; 676; 143; 156; 158; 312; 411; 411; 444; 444

Post-translational modifications (6): 74, 100, 401, 564, 970, 534

Mutagenesis-validated functional residues (2):

Position	Phenotype
154	six-fold decrease in sensitivity for calcium.
459–460	abolished enzyme activity and ability to promote histone succinylation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6783984	Glycine degradation
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-9853506	OGDH complex synthesizes succinyl-CoA from 2-OG

MSigDB gene sets: 277 (showing top): ATF_B, GOBP_FOREBRAIN_NEURON_DEVELOPMENT, GOBP_HINDBRAIN_DEVELOPMENT, ELVIDGE_HYPOXIA_DN, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GGGTGGRR_PAX4_03, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (14): generation of precursor metabolites and energy (GO:0006091), glycolytic process (GO:0006096), tricarboxylic acid cycle (GO:0006099), 2-oxoglutarate metabolic process (GO:0006103), succinyl-CoA metabolic process (GO:0006104), cerebellar cortex development (GO:0021695), striatum development (GO:0021756), hippocampus development (GO:0021766), thalamus development (GO:0021794), pyramidal neuron development (GO:0021860), tangential migration from the subventricular zone to the olfactory bulb (GO:0022028), olfactory bulb mitral cell layer development (GO:0061034), 2-oxoglutarate decarboxylation to succinyl-CoA (GO:0120551), obsolete NADH metabolic process (GO:0006734)

GO Molecular Function (9): oxoglutarate dehydrogenase (succinyl-transferring) activity (GO:0004591), thiamine pyrophosphate binding (GO:0030976), heat shock protein binding (GO:0031072), metal ion binding (GO:0046872), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor (GO:0016624), oxidoreductase activity, acting on the aldehyde or oxo group of donors (GO:0016903)

GO Cellular Component (5): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), mitochondrial membrane (GO:0031966), oxoglutarate dehydrogenase complex (GO:0045252)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Glyoxylate metabolism and glycine degradation	1
Metabolism of proteins	1
Citric acid cycle (TCA cycle)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	5
aerobic respiration	2
olfactory bulb development	2
cation binding	2
protein binding	2
intracellular membrane-bounded organelle	2
mitochondrion	2
metabolic process	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
primary metabolic process	1
dicarboxylic acid metabolic process	1
acyl-CoA metabolic process	1
cerebellum development	1
subpallium development	1
pallium development	1
limbic system development	1
diencephalon development	1
pyramidal neuron differentiation	1
forebrain neuron development	1
telencephalon cell migration	1
tricarboxylic acid cycle	1
2-oxoglutarate metabolic process	1
succinyl-CoA biosynthetic process	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor	1
vitamin binding	1
anion binding	1
quaternary ammonium group binding	1
heterocyclic compound binding	1
sulfur compound binding	1

Protein interactions and networks

STRING

2726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OGDH	DLST	P36957	999
OGDH	DLD	P09622	995
OGDH	AGXT	P21549	842
OGDH	GRHPR	Q9UBQ7	824
OGDH	ACO2	Q99798	804
OGDH	SUCLG1	P53597	804
OGDH	MDH2	P40926	792
OGDH	CS	O75390	775
OGDH	IDH3A	P50213	772
OGDH	IDH2	P48735	767
OGDH	FH	P07954	747
OGDH	SUCLA2	Q9P2R7	742
OGDH	IDH1	O75874	735
OGDH	SDHA	P31040	726
OGDH	DLAT	P10515	721

IntAct

83 interactions, top by confidence:

A	B	Type	Score
DLD	PDHX	psi-mi:“MI:0914”(association)	0.880
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
KGD4	DLD	psi-mi:“MI:0914”(association)	0.640
HTT	OGDH	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	OGDH	psi-mi:“MI:0915”(physical association)	0.560
MAPK6	ECI2	psi-mi:“MI:0914”(association)	0.530
MCEE	CLUH	psi-mi:“MI:0914”(association)	0.530
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
SKIC3	OGDH	psi-mi:“MI:0915”(physical association)	0.400
MYLK4	OGDH	psi-mi:“MI:0915”(physical association)	0.400
OGDH	PLSCR1	psi-mi:“MI:0915”(physical association)	0.370
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
HDAC6	GLOD5	psi-mi:“MI:0914”(association)	0.350
CAPZA2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ORF70	PDHX	psi-mi:“MI:0914”(association)	0.350

BioGRID (286): OGDH (Affinity Capture-RNA), OGDH (Affinity Capture-RNA), OGDH (Affinity Capture-RNA), OGDH (Affinity Capture-MS), PLSCR1 (Two-hybrid), OGDH (Affinity Capture-RNA), ATP5H (Co-fractionation), COX5A (Co-fractionation), CYC1 (Co-fractionation), DLAT (Co-fractionation), DLST (Co-fractionation), NDUFS4 (Co-fractionation), OGDH (Co-fractionation), OGDH (Co-fractionation), OGDH (Co-fractionation)

ESM2 similar proteins: A0PVU7, A0R0B0, A0R2B1, A1KI36, A1TDK2, A1UK81, A3Q3N5, A5U1U6, A5VSQ0, A6WXF0, A7GMD4, A7Z5J9, A9M8Q9, A9VJX9, B0CIS7, B2S877, B7HH19, B7IM94, C0RFG8, P0AFG3, P0AFG4, P0AFG5, P19543, P45303, P52647, P52965, P9WIS4, P9WIS5, Q02218, Q148N0, Q1B4V6, Q2RMD6, Q2YLS2, Q53046, Q57AX5, Q59097, Q59106, Q5L172, Q5R9L8, Q5RCB8

Diamond homologs: A0PVU7, A0R2B1, A1KI36, A1TDK2, A1UK81, A3Q3N5, A5ISU5, A5U1U6, A5VSQ0, A6QGW6, A6U1N4, A6WXF0, A7GMD4, A7X295, A7Z5J9, A8FE66, A8Z3Z0, A9M8Q9, A9VJX9, B0CIS7, B2S877, B7HH19, B7I0H2, B7IM94, B7JEU9, B9IU58, C0RFG8, C1ELG5, C3LAU3, C3P487, C4L3W2, C5D802, D3ZQD3, O61199, O74378, P0AFG3, P0AFG4, P0AFG5, P0C601, P20707

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
OGDH	“form complex”	OGDC	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

278 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	107
Likely benign	98
Benign	19

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1331346	NM_002541.4(OGDH):c.959A>G (p.Asn320Ser)	Pathogenic
2443830	NM_002541.4(OGDH):c.890C>A (p.Ser297Tyr)	Pathogenic
2443831	NM_002541.4(OGDH):c.566C>T (p.Pro189Leu)	Pathogenic
2443832	NM_002541.4(OGDH):c.935G>A (p.Arg312Lys)	Pathogenic
3340144	NM_002541.4(OGDH):c.1669-9A>G	Likely pathogenic

SpliceAI

3901 predictions. Top by Δscore:

Variant	Effect	Δscore
7:44645325:A:AG	acceptor_gain	1.0000
7:44645326:G:GG	acceptor_gain	1.0000
7:44645326:GT:G	acceptor_gain	1.0000
7:44645326:GTC:G	acceptor_gain	1.0000
7:44645326:GTCA:G	acceptor_gain	1.0000
7:44645326:GTCAT:G	acceptor_gain	1.0000
7:44645515:TCAGG:T	donor_loss	1.0000
7:44645516:CAGG:C	donor_loss	1.0000
7:44645517:AGGTA:A	donor_loss	1.0000
7:44645518:GGTAA:G	donor_loss	1.0000
7:44645519:G:A	donor_loss	1.0000
7:44645520:T:A	donor_loss	1.0000
7:44647852:GCTCT:G	donor_gain	1.0000
7:44666851:GGTAA:G	donor_loss	1.0000
7:44666852:GTAAG:G	donor_loss	1.0000
7:44666853:T:A	donor_loss	1.0000
7:44673785:A:AG	acceptor_gain	1.0000
7:44673785:AGA:A	acceptor_loss	1.0000
7:44673785:AGAT:A	acceptor_gain	1.0000
7:44673786:G:GA	acceptor_loss	1.0000
7:44673786:G:GG	acceptor_gain	1.0000
7:44673786:GAT:G	acceptor_gain	1.0000
7:44673786:GATG:G	acceptor_gain	1.0000
7:44673937:ACCAG:A	donor_loss	1.0000
7:44673938:CCAGG:C	donor_loss	1.0000
7:44673939:CAGG:C	donor_loss	1.0000
7:44673940:AG:A	donor_loss	1.0000
7:44673941:GG:G	donor_loss	1.0000
7:44673942:G:T	donor_loss	1.0000
7:44673943:T:A	donor_loss	1.0000

AlphaMissense

6762 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:44645330:T:A	W76R	1.000
7:44645330:T:C	W76R	1.000
7:44647663:G:T	G141W	1.000
7:44647664:G:A	G141E	1.000
7:44666847:T:C	L210P	1.000
7:44673808:G:T	G219W	1.000
7:44673809:G:A	G219E	1.000
7:44674454:T:C	F278L	1.000
7:44674456:T:A	F278L	1.000
7:44674456:T:G	F278L	1.000
7:44674466:G:C	G282R	1.000
7:44674557:G:T	R312I	1.000
7:44675179:G:A	G313R	1.000
7:44675179:G:C	G313R	1.000
7:44675179:G:T	G313W	1.000
7:44675180:G:A	G313E	1.000
7:44675180:G:T	G313V	1.000
7:44675190:C:A	N316K	1.000
7:44675190:C:G	N316K	1.000
7:44675239:T:C	F333L	1.000
7:44675241:C:A	F333L	1.000
7:44675241:C:G	F333L	1.000
7:44675988:T:C	Y349H	1.000
7:44675991:C:A	H350N	1.000
7:44675991:C:G	H350D	1.000
7:44681845:C:A	N444K	1.000
7:44681845:C:G	N444K	1.000
7:44693831:T:C	F448L	1.000
7:44693833:C:A	F448L	1.000
7:44693833:C:G	F448L	1.000

dbSNP variants (sampled 300 via entrez): RS1000011629 (7:44689375 C>G), RS1000035543 (7:44682293 G>A), RS1000130570 (7:44669703 T>C), RS1000136731 (7:44706408 G>A), RS1000250446 (7:44672591 C>A,T), RS1000269423 (7:44671077 G>A), RS1000285098 (7:44642781 G>A), RS1000287647 (7:44702146 G>T), RS1000302583 (7:44706681 C>G), RS1000364177 (7:44618591 T>C,G), RS1000390165 (7:44682688 TA>T,TAA), RS1000425791 (7:44624937 T>C), RS1000444487 (7:44636498 AGACT>A), RS1000449960 (7:44684552 T>A,C), RS1000485413 (7:44604959 A>G)

Disease associations

OMIM: gene MIM:613022 | disease phenotypes: MIM:203740

GenCC curated gene-disease

Disease	Classification	Inheritance
oxoglutaricaciduria	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (1): oxoglutaricaciduria (MONDO:0008759)

Orphanet (1): Oxoglutaric aciduria (Orphanet:31)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000238	Hydrocephalus
HP:0000750	Delayed speech and language development
HP:0000816	Abnormality of Krebs cycle metabolism
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001276	Hypertonia
HP:0001310	Dysmetria
HP:0001332	Dystonia
HP:0001942	Metabolic acidosis
HP:0002063	Rigidity
HP:0002066	Gait ataxia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002119	Ventriculomegaly
HP:0002151	Increased circulating lactate concentration
HP:0002194	Delayed gross motor development
HP:0002317	Unsteady gait
HP:0002527	Falls
HP:0003202	Skeletal muscle atrophy
HP:0003593	Infantile onset
HP:0003700	Generalized amyotrophy
HP:0003819	Death in childhood
HP:0004322	Short stature
HP:0004902	Congenital lactic acidosis
HP:0010286	Abnormal salivary gland morphology
HP:0012401	Abnormal urine alpha-ketoglutarate concentration
HP:0100022	Abnormality of movement

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003825_8	Systolic blood pressure change trajectory	3.000000e-07
GCST004747_10	Lung cancer in never smokers	9.000000e-06
GCST010204_17	Low density lipoprotein cholesterol levels	5.000000e-50
GCST012490_429	Femur bone mineral density x serum urate levels interaction	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006944	systolic blood pressure change measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536582	Alpha-ketoglutarate dehydrogenase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2816 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.61	Kd	24.7	nM	CHEMBL3752910
7.61	ED50	24.7	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148911: Binding affinity to human OGDH incubated for 45 mins by Kinobead based pull down assay	kd	0.0247	uM

CTD chemical–gene interactions

63 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
bisphenol A	decreases expression, increases expression	3
Air Pollutants, Occupational	decreases expression, affects expression	2
Methotrexate	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	increases expression	1
testosterone enanthate	affects expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	increases expression	1
zinc chromate	decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
acipimox	decreases expression	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
kahweol	decreases activity, decreases reaction	1
chromium hexavalent ion	increases abundance, decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651953	Binding	Binding affinity to human OGDH incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_W922	THJ-29T	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.