DLST

Summary

DLST (dihydrolipoamide S-succinyltransferase, HGNC:2911) is a protein-coding gene on chromosome 14q24.3, encoding Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial (P36957). Dihydrolipoamide succinyltransferase (E2) component of the 2-oxoglutarate dehydrogenase complex. It is a selective cancer dependency (DepMap: 27.6% of cell lines).

This gene encodes a mitochondrial protein that belongs to the 2-oxoacid dehydrogenase family. This protein is one of the three components (the E2 component) of the 2-oxoglutarate dehydrogenase complex that catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 1743 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary pheochromocytoma-paraganglioma (Supportive, GenCC) — +2 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 177 total
• GTEx eGene: eQTL in 12 tissues, sQTL in 6 (q < 0.05)
• Phenotypes (HPO): 55
• Cancer dependency (DepMap): dependent in 27.6% of screened cell lines
• Constraint (gnomAD): pLI 0.99 (loss-of-function intolerant), LOEUF 0.49 (moderately constrained)
• MANE Select transcript: NM_001933
• Interaction hub: 1,948 STRING partners (top 8% of genes corpus-wide)
• Notable: 177 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2911
Approved symbol	DLST
Name	dihydrolipoamide S-succinyltransferase
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	OGDC-E2, KGD2
Ensembl gene	ENSG00000119689
Ensembl biotype	protein_coding
OMIM	126063
Entrez	1743

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 21 protein_coding, 7 nonsense_mediated_decay, 6 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000334220

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 4, TSL 3: 4, TSL 4: 3, TSL 5: 2

ENST00000334220, ENST00000238671, ENST00000550473, ENST00000554612, ENST00000554806, ENST00000555071, ENST00000555089, ENST00000555190, ENST00000555459, ENST00000555492, ENST00000555988, ENST00000556190, ENST00000556460, ENST00000556582, ENST00000557012, ENST00000626051, ENST00000875048, ENST00000875049, ENST00000875050, ENST00000875051, ENST00000875052, ENST00000875053, ENST00000875054, ENST00000875055, ENST00000875056, ENST00000875057, ENST00000875058, ENST00000875059, ENST00000875060, ENST00000875061, ENST00000987012, ENST00001068913, ENST00001116742, ENST00001116743, ENST00001140367

RefSeq mRNA: 2 — MANE Select: NM_001933 NM_001244883, NM_001933

CCDS: CCDS9833

Canonical transcript exons

ENST00000334220 — 15 exons

Exon	Start	End
ENSE00002430505	74902196	74903743
ENSE00003463257	74889095	74889147
ENSE00003483814	74885586	74885634
ENSE00003492745	74882591	74882624
ENSE00003504830	74889275	74889349
ENSE00003575672	74899923	74899996
ENSE00003579414	74900289	74900372
ENSE00003623164	74901066	74901233
ENSE00003631601	74894312	74894409
ENSE00003644648	74881916	74882016
ENSE00003662356	74891056	74891167
ENSE00003664753	74892834	74892986
ENSE00003680070	74889897	74889952
ENSE00003682850	74898369	74898499
ENSE00003684143	74893348	74893424

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 97.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.3122 / max 472.9507, expressed in 1824 samples.

Highest expression (Bgee): apex of heart, adrenal gland cortex, adrenal gland, heart left ventricle, gastrocnemius.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DLST is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

18 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	7.0e-103	+0.42	14:74901104:C:T
Heart Left Ventricle	eqtl	1.4e-06	+0.11	14:74863994:C:T
Brain Cerebellum	sqtl	3.9e-06	+0.65	14:74880338:A:G
Adipose Subcutaneous	sqtl	8.5e-06	-0.24	14:74785884:T:C
Esophagus Mucosa	eqtl	1.0e-05	+0.16	14:74695281:C:T
Heart Atrial Appendage	eqtl	1.7e-05	+0.11	14:74865571:G:A
Testis	eqtl	1.1e-04	+0.09	14:74844109:G:C
Nerve Tibial	sqtl	8.2e-04	+0.19	14:74856211:G:A
Brain Cerebellum	eqtl	1.4e-03	+0.24	14:74872747:A:G
Brain Cerebellar Hemisphere	sqtl	1.5e-03	+0.54	14:74861544:T:C
Liver	eqtl	1.1e-02	+0.29	14:74887695:C:G
Thyroid	eqtl	1.3e-02	+0.09	14:74858077:A:G
Stomach	eqtl	2.0e-02	+0.20	14:74865977:C:G
Skin Not Sun Exposed Suprapubic	sqtl	2.3e-02	-0.25	14:74906772:T:C
Brain Hypothalamus	eqtl	2.6e-02	-0.53	14:75429503:C:T
Adipose Visceral Omentum	sqtl	2.7e-02	+0.26	14:74844626:C:T
Artery Coronary	eqtl	2.8e-02	-0.69	14:75715388:A:G
Brain Caudate basal ganglia	eqtl	3.1e-02	+0.14	14:74928726:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
140590	64.2478	1824
140589	2.0645	1459

Top tissues by expression

showing 100 of 297 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.50	gold quality
right adrenal gland cortex	UBERON:0035827	97.38	gold quality
right adrenal gland	UBERON:0001233	97.30	gold quality
heart left ventricle	UBERON:0002084	97.20	gold quality
gastrocnemius	UBERON:0001388	97.19	gold quality
left adrenal gland	UBERON:0001234	97.16	gold quality
cardiac ventricle	UBERON:0002082	97.15	gold quality
muscle of leg	UBERON:0001383	97.03	gold quality
left adrenal gland cortex	UBERON:0035825	96.98	gold quality
right atrium auricular region	UBERON:0006631	96.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.87	gold quality
lower esophagus	UBERON:0013473	96.86	gold quality
secondary oocyte	CL:0000655	96.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.78	gold quality
skin of leg	UBERON:0001511	96.75	gold quality
rectum	UBERON:0001052	96.74	gold quality
skin of abdomen	UBERON:0001416	96.70	gold quality
mucosa of stomach	UBERON:0001199	96.67	gold quality
transverse colon	UBERON:0001157	96.65	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.57	gold quality
heart	UBERON:0000948	96.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.39	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.37	gold quality
adrenal cortex	UBERON:0001235	96.36	gold quality
adrenal gland	UBERON:0002369	96.31	gold quality
endocervix	UBERON:0000458	96.30	gold quality
metanephros cortex	UBERON:0010533	96.24	gold quality
cardiac atrium	UBERON:0002081	96.19	gold quality
body of stomach	UBERON:0001161	96.17	gold quality
omental fat pad	UBERON:0010414	96.10	gold quality
peritoneum	UBERON:0002358	96.08	gold quality
stromal cell of endometrium	CL:0002255	96.03	gold quality
small intestine	UBERON:0002108	95.97	gold quality
body of uterus	UBERON:0009853	95.97	gold quality
right ovary	UBERON:0002118	95.85	gold quality
esophagus	UBERON:0001043	95.84	gold quality
heart right ventricle	UBERON:0002080	95.82	gold quality
ectocervix	UBERON:0012249	95.82	gold quality
tibial nerve	UBERON:0001323	95.81	gold quality
right lung	UBERON:0002167	95.81	gold quality
mucosa of transverse colon	UBERON:0004991	95.80	gold quality
popliteal artery	UBERON:0002250	95.78	gold quality
tibial artery	UBERON:0007610	95.78	gold quality
left ovary	UBERON:0002119	95.77	gold quality
left uterine tube	UBERON:0001303	95.76	gold quality
upper lobe of left lung	UBERON:0008952	95.62	gold quality
gall bladder	UBERON:0002110	95.61	gold quality
descending thoracic aorta	UBERON:0002345	95.54	gold quality
left coronary artery	UBERON:0001626	95.52	gold quality
aorta	UBERON:0000947	95.49	gold quality
minor salivary gland	UBERON:0001830	95.48	gold quality
right coronary artery	UBERON:0001625	95.44	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.38	gold quality
right lobe of thyroid gland	UBERON:0001119	95.37	gold quality
sigmoid colon	UBERON:0001159	95.37	gold quality
stomach	UBERON:0000945	95.27	gold quality
colon	UBERON:0001155	95.24	gold quality
thoracic aorta	UBERON:0001515	95.22	gold quality
ascending aorta	UBERON:0001496	95.19	gold quality
adult mammalian kidney	UBERON:0000082	95.17	gold quality
intestine	UBERON:0000160	95.14	gold quality
left lobe of thyroid gland	UBERON:0001120	95.12	gold quality
colonic epithelium	UBERON:0000397	95.10	gold quality
muscle organ	UBERON:0001630	95.05	gold quality
skeletal muscle organ	UBERON:0014892	95.05	gold quality
right uterine tube	UBERON:0001302	95.04	gold quality
left ventricle myocardium	UBERON:0006566	95.03	gold quality
right lobe of liver	UBERON:0001114	95.02	gold quality
coronary artery	UBERON:0001621	95.02	gold quality
esophagus mucosa	UBERON:0002469	94.97	gold quality
body of pancreas	UBERON:0001150	94.95	gold quality
large intestine	UBERON:0000059	94.94	gold quality
islet of Langerhans	UBERON:0000006	94.90	gold quality
vagina	UBERON:0000996	94.89	gold quality
lower esophagus mucosa	UBERON:0035834	94.86	gold quality
oocyte	CL:0000023	94.80	gold quality
granulocyte	CL:0000094	94.78	gold quality
zone of skin	UBERON:0000014	94.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.70	gold quality
upper lobe of lung	UBERON:0008948	94.52	gold quality
thyroid gland	UBERON:0002046	94.43	gold quality
body of tongue	UBERON:0011876	94.38	gold quality
smooth muscle tissue	UBERON:0001135	94.29	gold quality
ganglionic eminence	UBERON:0004023	94.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.17	gold quality
triceps brachii	UBERON:0001509	94.04	gold quality
duodenum	UBERON:0002114	93.96	gold quality
cerebellar hemisphere	UBERON:0002245	93.94	gold quality
adipose tissue	UBERON:0001013	93.81	gold quality
fundus of stomach	UBERON:0001160	93.78	gold quality
decidua	UBERON:0002450	93.72	gold quality
cerebellar cortex	UBERON:0002129	93.70	gold quality
ventricular zone	UBERON:0003053	93.62	gold quality
saliva-secreting gland	UBERON:0001044	93.60	gold quality
adenohypophysis	UBERON:0002196	93.54	gold quality
cortical plate	UBERON:0005343	93.54	gold quality
ovary	UBERON:0000992	93.48	gold quality
pancreas	UBERON:0001264	93.46	gold quality
mouth mucosa	UBERON:0003729	93.46	gold quality
monocyte	CL:0000576	93.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.04

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	209.4
Skeletal muscle	tissue	135.5	medium
Heart muscle	tissue	104.6	medium
Kidney	tissue	93.8	high
Frontal cortex	tissue	80.4
Parathyroid gland	tissue	74.0	high
Bone marrow	tissue	70.8	medium
Caudate putamen	tissue	69.8
Liver	tissue	64.5	high
Cervix	tissue	58.5	high
Adrenal gland	tissue	57.9	high
Adipose tissue	tissue	57.1	medium
Rectum	tissue	55.7	high
Duodenum	tissue	55.3	medium
Choroid plexus	tissue	54.5
Cerebral cortex	tissue	52.8	medium
Colon	tissue	52.8	medium
Small intestine	tissue	52.8	medium
Somatosensory cortex	tissue	52.8
Superior colliculi	tissue	52.5
Thalamus	tissue	51.8
Smooth muscle	tissue	48.7	low
Occipital cortex	tissue	48.7
Pons	tissue	48.5
Midbrain	tissue	48.2
Vagina	tissue	48.1	medium
Spinal cord	tissue	46.8
Medulla oblongata	tissue	45.9
Motor cortex	tissue	44.9
Esophagus	tissue	44.2	medium
Tonsil	tissue	42.8	medium
Prefrontal cortex	tissue	42.7
Placenta	tissue	42.1	medium
Temporal cortex	tissue	42.0
Substantia nigra	tissue	41.6
Hippocampal formation	tissue	41.4
Entorhinal cortex	tissue	41.4
Urinary bladder	tissue	41.2	medium
Seminal vesicle	tissue	40.9	high
Epididymis	tissue	40.7	medium
Putamen	tissue	40.6
Retrosplenial and cingulate cortex	tissue	40.2
Fallopian tube	tissue	40.1	high
Skin 1	tissue	39.9	medium
Thymus	tissue	39.6
Retrosplenial cortex	tissue	39.6
Stomach 1	tissue	39.4	medium
Ventral forebrain	tissue	39.3
Ovary	tissue	37.8	medium
Insular cortex	tissue	37.7
Thyroid gland	tissue	37.4	medium
Breast	tissue	37.2
Hypothalamus	tissue	36.4
Septum	tissue	36.1
Basal ganglia	tissue	36.0	medium
Periaqueductal gray	tissue	35.5
Cerebellum	tissue	35.2	high
Endometrium 1	tissue	34.7	medium
Lymph node	tissue	34.6	high
Lung	tissue	34.6	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (56.5), Ventral spinal cord (46.8), Dorsal hippocampus (40.7), Anterior thalamic nucleus, ventral (40.6), Posterior thalamic nucleus (40.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ARID4A, BMAL1, CEBPB, CEBPG, CLOCK, CREB1, E2F1, E2F3, ELK1, ESR1, ESR2, ETS1, FOXL2, GLI2, HES1, HSF2, ID1, ISL1, JUN, MYBL2, MYC, MYOD1, NCOA1, NFIL3, NFKB1, NFKB, NFYA, NR1I3, NR2F1, NR3C1, NR4A1, RARB, RELA, SNAI1, SP1, SP3, SREBF1

miRNA regulators (miRDB)

Targeting DLST by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 38 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-4632-5P	97.82	65.38	1470

Functional genomics

gnomAD constraint: pLI 0.989, LOEUF 0.489, missense Z 1.25 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000334220 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
14:74,881,954–74,889,290	129 / 90.9	1.42	no
14:74,889,291–74,891,118	35 / 70.5	0.50	no
14:74,891,119–74,894,400	162 / 162.0	1.00	no
14:74,894,401–74,902,327	186 / 260.4	0.71	no
DepMap (CRISPR cell-line fitness): dependent in 27.6% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): ES5 (-1.609), LP-1 (-1.502), KMS-11 (-1.459), RL95-2 (-1.445), SU-DHL-8 (-1.437), WSU-NHL (-1.297), YCUB-2 (-1.277), F-36P (-1.251), C32 (-1.185), KMCH-1 (-1.18), OCI-LY-19 (-1.176), HB11;19 (-1.167), RPMI 8226 (-1.154), CMS (-1.146), CHRF-288-11 (-1.144).

Literature-anchored findings (GeneRIF, showing 8)

• Data show that the dihydrolipoamide succinyltransferase gene is bifunctional, and truncated mRNA transcribed from it contributes to the biogenesis of the mitochondrial respiratory complexes. (PMID:12805207)
• Association between late-onset Alzheimer disease shows strong linkage disequilibrium across the DLST locus. (PMID:15038610)
• 2-oxoglutarate dehydrogenase complex (OGDHC), the key regulatory enzyme of Krebs cycle. [review] (PMID:22235656)
• ATP consumption is demonstrated in respiration-impaired isolated and in situ neuronal somal mitochondria from transgenic mice that exhibit a 20-48% decrease in alpha-ketoglutarate dehydrogenase activity. (PMID:23475850)
• RNAi knockdown of DLST led to decreased cell viability and induction of apoptosis in human T-ALL cell lines (PMID:26876595)
• five germline variants affecting DLST in eight unrelated individuals were identified; all except one were diagnosed with multiple pheochromocytomas and paragangliomas (PMID:30929736)
• Germline DLST Variants Promote Epigenetic Modifications in Pheochromocytoma-Paraganglioma. (PMID:33180916)
• Metabolic Enzyme DLST Promotes Tumor Aggression and Reveals a Vulnerability to OXPHOS Inhibition in High-Risk Neuroblastoma. (PMID:34233924)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dlst	ENSDARG00000014230
mus_musculus	Dlst	ENSMUSG00000004789
rattus_norvegicus	Dlst	ENSRNOG00000005061
drosophila_melanogaster	CG5214	FBGN0037891
caenorhabditis_elegans		WBGENE00020950

Paralogs (3): PDHX (ENSG00000110435), DBT (ENSG00000137992), DLAT (ENSG00000150768)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1926170) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Escherichia coli K-12	P0AFG6	100.0%	Diamond
Escherichia coli O157:H7	P0AFG7	100.0%	Diamond
Mycobacterium tuberculosis variant bovis AF2122/97	P65634	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WIS6	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WIS7	100.0%	Diamond
Staphylococcus aureus subsp. aureus USA300	Q2FH26	100.0%	Diamond
Staphylococcus aureus subsp. aureus NCTC 8325	Q2FYM2	100.0%	Diamond
Staphylococcus aureus subsp. aureus COL	Q5HG07	100.0%	Diamond
Staphylococcus aureus subsp. aureus MSSA476	Q6G9E9	100.0%	Diamond
Staphylococcus aureus subsp. aureus N315	Q7A5N4	100.0%	Diamond
Staphylococcus aureus subsp. aureus MW2	Q8NWR7	100.0%	Diamond
Staphylococcus aureus subsp. aureus Mu50	Q99U75	100.0%	Diamond
Staphylococcus epidermidis RP62A	Q5HQ74	99.8%	Diamond
Staphylococcus epidermidis ATCC 12228	Q8CT13	99.8%	Diamond
Staphylococcus aureus RF122	Q2YY06	98.8%	Diamond
Staphylococcus aureus subsp. aureus MRSA252	Q6GGZ6	98.8%	Diamond
Rickettsia felis Marseille-URRWFXCal2	Q4UKI7	93.0%	Diamond
Rickettsia conorii str. Malish 7	Q92J43	93.0%	Diamond
Rickettsia typhi str. Wilmington	Q68XI8	92.5%	Diamond
Rickettsia prowazekii str. Madrid E	Q9ZDY4	92.5%	Diamond
Bos taurus	P11179	91.0%	Diamond
Sus scrofa	Q9N0F1	88.4%	Diamond
Chlamydia trachomatis D/UW-3/CX	O84125	87.8%	Diamond
Rickettsia bellii RML369-C	Q1RHI5	87.1%	Diamond
Azotobacter vinelandii	P20708	86.8%	Diamond
Pseudomonas aeruginosa PAO1	Q9I3D2	86.6%	Diamond
Bartonella quintana str. Toulouse	Q6FYD4	86.1%	Diamond
Bartonella vinsonii subsp. berkhoffii	Q8GCY1	86.1%	Diamond
Pseudomonas putida	P31051	84.5%	Diamond
Mesocricetus auratus	P86197	82.6%	Diamond
Haemophilus influenzae Rd KW20	P45302	81.0%	Diamond
Staphylococcus haemolyticus JCSC1435	Q4L6C3	77.6%	Diamond
Takifugu rubripes	Q90512	76.5%	Diamond
Staphylococcus saprophyticus subsp. saprophyticus ATCC 15305 = NCTC 7292	Q49XM4	75.5%	Diamond
Geobacillus stearothermophilus	P11961	74.2%	Diamond
Bacillus subtilis subsp. subtilis str. 168	P21883	73.5%	Diamond
Buchnera aphidicola str. Sg (Schizaphis graminum)	Q8K9N2	72.4%	Diamond
Mycoplasmoides pneumoniae M129	P75392	71.2%	Diamond
Fusarium oxysporum f. sp. lycopersici 4287	A0A0D2Y5A7	70.9%	Diamond
Arabidopsis thaliana	Q9FLQ4	70.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PROX2	protein-coding	283571
RPS6KL1	protein-coding	83694
MLH3	protein-coding	27030
PGF	protein-coding	5228
EIF2B2	protein-coding	8892
YLPM1	protein-coding	56252

Protein

Protein identifiers

Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial — P36957 (reviewed: P36957)

Alternative names: 2-oxoglutarate dehydrogenase complex component E2, Dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex, E2K

All UniProt accessions (8): B7ZAZ8, G3V3F0, G3V498, G3V5L9, G3V5M3, H0YJF9, P36957, Q86SW4

UniProt curated annotations — full annotation on UniProt →

Function. Dihydrolipoamide succinyltransferase (E2) component of the 2-oxoglutarate dehydrogenase complex. The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). The 2-oxoglutarate dehydrogenase complex is 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. 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 matrix. Nucleus.

Disease relevance. Pheochromocytoma/paraganglioma syndrome 7 (PPGL7) [MIM:618475] A form of pheochromocytoma/paraganglioma syndrome, a tumor predisposition syndrome characterized by the development of neuroendocrine tumors, usually in adulthood. Pheochromocytomas are catecholamine-producing tumors that arise from chromaffin cells in the adrenal medulla. Paragangliomas develop from sympathetic paraganglia in the thorax, abdomen, and pelvis, as well as from parasympathetic paraganglia in the head and neck. PPGL7 tumors are generally benign, tend to be abdominal, and often secrete normetanephrine. PPGL7 inheritance is autosomal dominant. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Cofactor. Binds 1 lipoyl cofactor covalently.

Pathway. Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 6/6. Carbohydrate metabolism; tricarboxylic acid cycle.

Similarity. Belongs to the 2-oxoacid dehydrogenase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P36957-1	1	yes
P36957-2	2

RefSeq proteins (2): NP_001231812, NP_001924* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000089	Biotin_lipoyl	Domain
IPR001078	2-oxoacid_DH_actylTfrase	Domain
IPR003016	2-oxoA_DH_lipoyl-BS	Binding_site
IPR006255	SucB	Family
IPR011053	Single_hybrid_motif	Homologous_superfamily
IPR023213	CAT-like_dom_sf	Homologous_superfamily
IPR050537	2-oxoacid_dehydrogenase	Family

Pfam: PF00198, PF00364

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)

• N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + succinyl-CoA = N(6)-[(R)-S(8)-succinyldihydrolipoyl]-L-lysyl-[protein] + CoA (RHEA:15213)

UniProt features (54 total): helix 11, strand 9, modified residue 8, sequence variant 6, sequence conflict 4, turn 4, splice variant 2, mutagenesis site 2, compositionally biased region 2, active site 2, transit peptide 1, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
6H05	Cryo-electron microscopic structure of the dihydrolipoamide succinyltransferase (E2) …	ELECTRON MICROSCOPY	2.9
9RCA	Solution NMR structure of the lipoyl domain of the E2 subunit in the human …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36957-F1	77.40	0.44

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Citric acid cycle related proteins, Disease related genes, Potential drug targets, Human disease related genes, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol; mitochondria

Antibody reliability (HPA): IH supported · IF supported

Functional residue map

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

Catalytic / active sites (2)

Position	Role
424
428

Post-translational modifications (8)

Type	Positions
N6-acetyllysine	154, 267, 272, 273, 277, 307
Phosphoserine	81
N6-lipoyllysine	110

Mutagenesis-validated functional residues (2)

Position	Phenotype
224–226	reduced nuclear localization of the 2-oxoglutarate dehydrogenase complex. reduced histone succinylation.
424	loss of dihydrolipoyllysine-residue succinyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 12; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

12 pathways:

ID	Pathway	Evidence
R-HSA-6783984	Glycine degradation	curated
R-HSA-9858328	OADH complex synthesizes glutaryl-CoA from 2-OA	curated
R-HSA-9853506	OGDH complex synthesizes succinyl-CoA from 2-OG	curated
R-HSA-9857492	Protein lipoylation	curated
R-HSA-1428517	Aerobic respiration and respiratory electron transport	—
R-HSA-71403	Citric acid cycle (TCA cycle)	—
R-HSA-389661	Glyoxylate metabolism and glycine degradation	—
R-HSA-71064	Lysine catabolism	—
R-HSA-1430728	Metabolism	—
R-HSA-71291	Metabolism of amino acids and derivatives	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 339 (showing top): GGGACCA_MIR133A_MIR133B, E2F_Q4_01, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, CREBP1_Q2, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, ONKEN_UVEAL_MELANOMA_UP, E2F_Q3

GO Biological Process (5): generation of precursor metabolites and energy (GO:0006091), tricarboxylic acid cycle (GO:0006099), 2-oxoglutarate metabolic process (GO:0006103), succinyl-CoA metabolic process (GO:0006104), 2-oxoglutarate decarboxylation to succinyl-CoA (GO:0120551)

GO Molecular Function (5): dihydrolipoyllysine-residue succinyltransferase activity (GO:0004149), acyltransferase activity (GO:0016746), protein binding (GO:0005515), transferase activity (GO:0016740), dihydrolipoyllysine-residue glutaryltransferase activity (GO:0120571)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), membrane (GO:0016020), oxoglutarate dehydrogenase complex (GO:0045252), oxoadipate dehydrogenase complex (GO:0160167)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Metabolism	2
Metabolism of amino acids and derivatives	2
Glyoxylate metabolism and glycine degradation	1
Citric acid cycle (TCA cycle)	1
Post-translational protein modification	1
Lysine catabolism	1
Metabolism of proteins	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

23 GO namespaces:

Category	Terms
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
alpha-ketoacid dehydrogenase complex	2
transferase complex	2
metabolic process	1
aerobic respiration	1
primary metabolic process	1
dicarboxylic acid metabolic process	1
acyl-CoA metabolic process	1
tricarboxylic acid cycle	1
2-oxoglutarate metabolic process	1
succinyl-CoA biosynthetic process	1
S-succinyltransferase activity	1
catalytic activity, acting on a protein	1
transferase activity	1
binding	1
catalytic activity	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
nuclear lumen	1
cytoplasm	1
mitochondrion	1
intracellular organelle lumen	1
tricarboxylic acid cycle heteromeric enzyme complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
tricarboxylic acid cycle	BP	mutant phenotype
membrane	CC	high-throughput assay
mitochondrion	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
oxoadipate dehydrogenase complex	CC	direct assay
oxoglutarate dehydrogenase complex	CC	direct assay
acyltransferase activity	MF	mutant phenotype
dihydrolipoyllysine-residue succinyltransferase activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 1,948 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DLST	OGDH	Q02218	990
DLST	DLD	P09622	718
DLST	ACO2	Q99798	699
DLST	MDH2	P40926	664
DLST	DHTKD1	Q96HY7	637
DLST	OGDHL	Q9ULD0	632
DLST	IDH3A	P50213	602
DLST	ACO1	P21399	602
DLST	SUCLA2	Q9P2R7	600
DLST	FH	P07954	590
DLST	SUCLG1	P53597	590
DLST	IDH2	P48735	587
DLST	CS	O75390	585
DLST	IDH1	O75874	573
DLST	IDH3B	O43837	561

IntAct

Human interaction partners of DLST in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 91 partners by confidence:

Partner	Interaction type	MIscore	Records
PSMC4	physical association	0.670	3
ARHGEF28	physical association	0.560	3
C1orf216	physical association	0.560	3
CAMTA2	physical association	0.560	3
CNOT3	physical association	0.560	3
CRELD2	physical association	0.560	3
DNASE1L1	physical association	0.560	3
DRC7	physical association	0.560	3
EGFL8	physical association	0.560	3
EPCAM	physical association	0.560	3
EVA1B	physical association	0.560	3
FAHD2A	physical association	0.560	3
FUT2	physical association	0.560	3
GJA5	physical association	0.560	3
GNAO1	physical association	0.560	3
HLA-DRB3	physical association	0.560	3
HSD3B1	physical association	0.560	3
HTT	physical association	0.560	3
HUWE1	physical association	0.560	3
IDH1	physical association	0.560	3
ISY1	physical association	0.560	3
KIAA1683	physical association	0.560	3
KLRC1	physical association	0.560	3
LEG1	physical association	0.560	3
LGALS1	physical association	0.560	3
LGALS8	physical association	0.560	3
MAGEA2	physical association	0.560	3
MAVS	physical association	0.560	3
MFI	physical association	0.560	3
MGC39372	physical association	0.560	3

BioGRID (558 interactions; top human partners by supporting records): DLD (Affinity Capture-MS; 5 records), OGDH (Co-fractionation; 5 records), SIAH2 (Biochemical Activity; 4 records), PRNP (Affinity Capture-MS; 3 records), AARS2 (Affinity Capture-MS; 2 records), ATP5O (Affinity Capture-MS; 2 records), CAPZA2 (Affinity Capture-MS; 2 records), CAPZB (Affinity Capture-MS; 2 records), CCT7 (Affinity Capture-MS; 2 records), CFTR (Affinity Capture-MS; 2 records), COX4I1 (Proximity Label-MS; 2 records), CS (Proximity Label-MS; 2 records), DLAT (Co-fractionation; 2 records), DYNC1H1 (Affinity Capture-MS; 2 records), GRSF1 (Proximity Label-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
DLST	“form complex”	OGDC	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
KAT2A-Oxoglutarate dehydrogenase complex	4	DLST, KAT2A, OGDH, DLD

Disease & clinical

Genetic variants

Variant evidence for DLST: 177 ClinVar records (0 pathogenic / likely pathogenic); 7 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	47
Benign	12

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 984):

Position(s)	Effect	Δscore	Sites
14:74882017	donor_loss	1.0000	2
14:74889261	acceptor_gain	1.0000
14:74889265	acceptor_gain	1.0000
14:74889273–74889274	acceptor_loss	1.0000	6
14:74889350–74889351	donor_loss	1.0000	5
14:74889953–74889954	donor_loss	1.0000	5
14:74891158	donor_gain	1.0000
14:74892832–74892833	acceptor_loss	1.0000	6
14:74892987–74892988	donor_loss	1.0000	4
14:74893346	acceptor_loss	1.0000

AlphaMissense

1,202 missense substitutions predicted likely pathogenic (of 2,936 scored), across 276 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M416	9	0.922	0.991
M281	9	0.834	0.985
H424	8	0.996	0.999
D423	8	0.992	0.998
D428	8	0.986	0.996
D109	8	0.982	0.998
F78	8	0.979	0.997
F284	8	0.971	0.996
F369	8	0.957	0.998
D86	8	0.945	0.985
H397	8	0.942	0.993
F141	8	0.934	0.998
D316	8	0.920	0.988
F251	8	0.911	0.995
F435	8	0.898	0.989
D100	8	0.882	0.983
D445	8	0.843	0.975
D363	8	0.802	0.940
D95	8	0.777	0.946
W89	7	0.991	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.55e-08
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	6.36e-05

Disease associations

OMIM: gene MIM:126063 | disease phenotypes:

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
hereditary pheochromocytoma-paraganglioma	Supportive	Autosomal dominant
pheochromocytoma/paraganglioma syndrome 7	Limited	Autosomal dominant	2
pyruvate dehydrogenase E1-alpha deficiency	No Known Disease Relationship	Autosomal recessive

Mondo (3): pheochromocytoma/paraganglioma syndrome 7 (MONDO:0032771), pyruvate dehydrogenase E1-alpha deficiency (MONDO:0010717), hereditary pheochromocytoma-paraganglioma (MONDO:0017366)

HPO phenotypes

55 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000096	Glomerular sclerosis
HP:0000405	Conductive hearing impairment
HP:0000526	Aniridia
HP:0000740	Episodic paroxysmal anxiety
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000980	Pallor
HP:0001069	Episodic hyperhidrosis
HP:0001095	Hypertensive retinopathy
HP:0001278	Orthostatic hypotension
HP:0001279	Syncope
HP:0001293	Cranial nerve compression
HP:0001337	Tremor
HP:0001342	Cerebral hemorrhage
HP:0001605	Vocal cord paralysis
HP:0001618	Dysphonia
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001824	Weight loss
HP:0001962	Palpitations
HP:0002018	Nausea
HP:0002019	Constipation
HP:0002331	Recurrent paroxysmal headache
HP:0002574	Episodic abdominal pain
HP:0002640	Hypertension associated with pheochromocytoma
HP:0002666	Pheochromocytoma
HP:0002668	Paraganglioma
HP:0002864	Paraganglioma of head and neck
HP:0003072	Hypercalcemia
HP:0003074	Hyperglycemia
HP:0003345	Elevated urinary norepinephrine level
HP:0003528	Elevated circulating calcitonin concentration
HP:0003574	Positive regitine blocking test
HP:0003581	Adult onset
HP:0003639	Elevated urinary epinephrine level
HP:0003829	Typified by incomplete penetrance
HP:0005584	Renal cell carcinoma
HP:0006737	Extraadrenal pheochromocytoma
HP:0006748	Adrenal pheochromocytoma
HP:0008629	Pulsatile tinnitus
HP:0009711	Retinal capillary hemangioma
HP:0010532	Paroxysmal vertigo
HP:0011703	Sinus tachycardia
HP:0011979	Elevated urinary dopamine level
HP:0012222	Arachnoid hemangiomatosis
HP:0012378	Fatigue
HP:0012819	Myocarditis
HP:0025269	Panic attack
HP:0031284	Flushing
HP:0031500	Abdominal mass
HP:0100735	Hypertensive crisis
HP:0100749	Chest pain

GWAS associations

7 associations:

Study	Trait	p-value
GCST90000025_143	Appendicular lean mass	6e-27
GCST90002381_503	Eosinophil count	5e-10
GCST005238_3	Mood instability	3e-9
GCST005839_15	Depression	4e-9
GCST009600_1	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	2e-8
GCST005237_3	Mood instability	1e-6
GCST001734_8	Non-small cell lung cancer	7e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0008475	mood instability measurement
EFO:0004980	appendicular lean mass
EFO:0004842	eosinophil count

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C564071	Pyruvate Dehydrogenase E1 Alpha Deficiency *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066909 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.73	Kd	1864	nM	CHEMBL5653589
5.73	ED50	1864	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148245: Binding affinity to human DLST incubated for 45 mins by Kinobead based pull down assay	kd	1.8636	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
bisphenol S	increases expression	3
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
GSK-J4	increases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	increases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
decabromobiphenyl ether	increases expression	1
arsenite	increases reaction, affects binding	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
acipimox	increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
bisphenol AF	increases expression	1
Aspirin	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases expression	1
Cannabidiol	decreases expression	1
Clozapine	decreases expression	1
Cuprizone	decreases expression	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Isoniazid	increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651287	Binding	Binding affinity to human DLST 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*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

2 trials:

NCT	Phase	Status	Title
NCT05257005	Not specified	UNKNOWN	Natural History Study of Pyruvate Dehydrogenase Deficiency
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DLST across ~30M SureChEMBL compounds — explore on Sugi Predict.