SDHA

Summary

SDHA (succinate dehydrogenase complex flavoprotein subunit A, HGNC:10680) is a protein-coding gene on chromosome 5p15.33, encoding Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial (P31040). Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). It is a selective cancer dependency (DepMap: 24.6% of cell lines).

This gene encodes a major catalytic subunit of succinate-ubiquinone oxidoreductase, a complex of the mitochondrial respiratory chain. The complex is composed of four nuclear-encoded subunits and is localized in the mitochondrial inner membrane. Mutations in this gene have been associated with a form of mitochondrial respiratory chain deficiency known as Leigh Syndrome. A pseudogene has been identified on chromosome 3q29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6389 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary pheochromocytoma-paraganglioma (Definitive, ClinGen) — +10 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 3,323 total — 186 pathogenic, 97 likely-pathogenic
• Phenotypes (HPO): 188
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Cancer dependency (DepMap): dependent in 24.6% of screened cell lines
• MANE Select transcript: NM_004168

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10680
Approved symbol	SDHA
Name	succinate dehydrogenase complex flavoprotein subunit A
Location	5p15.33
Locus type	gene with protein product
Status	Approved
Aliases	FP, SDHF
Ensembl gene	ENSG00000073578
Ensembl biotype	protein_coding
OMIM	600857
Entrez	6389

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 32 protein_coding, 10 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000264932, ENST00000502379, ENST00000503674, ENST00000504309, ENST00000504824, ENST00000505555, ENST00000507266, ENST00000507522, ENST00000509082, ENST00000509420, ENST00000509564, ENST00000509632, ENST00000510361, ENST00000511810, ENST00000512962, ENST00000514027, ENST00000514233, ENST00000515752, ENST00000515815, ENST00000874233, ENST00000874234, ENST00000874235, ENST00000874236, ENST00000874237, ENST00000874238, ENST00000874239, ENST00000874240, ENST00000874241, ENST00000874242, ENST00000874243, ENST00000874244, ENST00000874245, ENST00000874246, ENST00000874247, ENST00000874248, ENST00000925263, ENST00000952707, ENST00000952708, ENST00000952709, ENST00000952710, ENST00000952711, ENST00000952712, ENST00000952713, ENST00000952714, ENST00000952715, ENST00000952716

RefSeq mRNA: 3 — MANE Select: NM_004168 NM_001294332, NM_001330758, NM_004168

CCDS: CCDS3853, CCDS77992, CCDS82985

Canonical transcript exons

ENST00000264932 — 15 exons

Exon	Start	End
ENSE00001742892	256334	257082
ENSE00003483620	250992	251103
ENSE00003487513	230876	231000
ENSE00003509516	240358	240476
ENSE00003524126	251338	251468
ENSE00003576167	235144	235339
ENSE00003590655	223482	223568
ENSE00003593538	236428	236599
ENSE00003597004	228185	228333
ENSE00003609834	233477	233645
ENSE00003626939	225883	226047
ENSE00003655301	224360	224521
ENSE00003686438	254393	254506
ENSE00003687557	225419	225562
ENSE00003845083	218320	218418

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.5767 / max 399.4308, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55459	48.4006	1825
55460	2.1760	1303

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.47	gold quality
heart left ventricle	UBERON:0002084	99.33	gold quality
mucosa of transverse colon	UBERON:0004991	99.04	gold quality
right atrium auricular region	UBERON:0006631	99.03	gold quality
skeletal muscle tissue	UBERON:0001134	99.00	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.89	gold quality
heart	UBERON:0000948	98.75	gold quality
gastrocnemius	UBERON:0001388	98.71	gold quality
duodenum	UBERON:0002114	98.71	gold quality
right lobe of liver	UBERON:0001114	98.65	gold quality
muscle organ	UBERON:0001630	98.60	gold quality
skeletal muscle organ	UBERON:0014892	98.60	gold quality
muscle of leg	UBERON:0001383	98.58	gold quality
right adrenal gland cortex	UBERON:0035827	98.53	gold quality
adult mammalian kidney	UBERON:0000082	98.49	gold quality
liver	UBERON:0002107	98.47	gold quality
right adrenal gland	UBERON:0001233	98.44	gold quality
primary visual cortex	UBERON:0002436	98.44	gold quality
cortex of kidney	UBERON:0001225	98.35	gold quality
left adrenal gland	UBERON:0001234	98.34	gold quality
left adrenal gland cortex	UBERON:0035825	98.33	gold quality
metanephros cortex	UBERON:0010533	98.31	gold quality
colonic epithelium	UBERON:0000397	98.19	gold quality
transverse colon	UBERON:0001157	98.18	gold quality
adrenal gland	UBERON:0002369	98.10	gold quality
muscle tissue	UBERON:0002385	98.08	gold quality
kidney	UBERON:0002113	97.90	gold quality
lower esophagus mucosa	UBERON:0035834	97.76	gold quality
right frontal lobe	UBERON:0002810	97.75	gold quality
colon	UBERON:0001155	97.71	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.25
E-MTAB-7606	no	547.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting SDHA, 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-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-4421	97.99	64.89	701
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-5699-3P	97.81	65.00	861
HSA-MIR-556-5P	97.75	66.17	473

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 24.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Review. Succinate dehydrogenase catalyses a step in the Krebs tricarboxylic-acid cycle. Inherited heterozygous mutations in the gene encoding this enzyme causes a predisposition to inherited neoplasia syndromes. (PMID:12612654)
• The SDHA variants that have increased in frequency during human evolution might, by influencing the regulation of cellular oxygen homeostasis, confer protection against certain environmental toxins or pathogens that are prevalent in Africa. (PMID:17376234)
• Phosphorylation of flavoprotein subunit ofsuccinate-ubiquinone reductase might be important for maintaining mitochondrial energy metabolism within the tumor microenvironment. (PMID:19644226)
• Mutations in electron Transport Complex II is associated with Leber hereditary optic neuropathy failing to compensate for impaired oxidative phosphorylation. (PMID:19836344)
• Decreased electron Transport Complex II activity is associated with ulcerative colitis. (PMID:20440543)
• Cells with Complex II defect may undergo a progressive mitochondrial dysfunction, characterized by Dcmit loss, Calcium overload and increased ROS, eventually leading to cell death. (PMID:20489732)
• study presents the association of a mutation in the SDHA gene with recessive neonatal isolated dilated cardiomyopathy in 15 patients of two large consanguineous Bedouin families (PMID:20551992)
• First report describing germline and somatic loss-of-function mutations in SDHA that are linked to the development of sporadic KIT/PDGFRA wild-type GISTs. (PMID:21505157)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Tumor-derived FH and SDH mutations accumulate fumarate and succinate, leading to enzymatic inhibition of multiple alpha-KG-dependent dioxygenases and consequent alterations of genome-wide histone and DNA methylation. (PMID:22677546)
• Loss of SDHA expression in gastrointestinal stromal tumor (GIST) reliably predicts the presence of SDHA mutations, which represent a relatively common cause of SDH-deficient GIST in adults. (PMID:22955521)
• This report represents the first example of SDHB mutation as a cause of inherited mitochondrial respiratory chain disease and extends the SDHA mutation spectrum in patients with isolated complex II deficiency. (PMID:22972948)
• A germline p.Arg31X nonsense SDHA mutation was identified in one of the six wild-type gastrointestinal stromal tumors cases. An additional SDHA missense mutation was identified in the extended KIT/PDGFRA WT GIST patients cohort. (PMID:22974104)
• Studies indicate that the pH change leads to the dissociation of SDHA and SDHB subunits from the remaining membrane-anchored subunits and the consequent block of enzymatic succinate-ubiquinone reductase (SQR) activity. (PMID:23000077)
• Loss of SDHA expression identifies SDHA mutations in succinate dehydrogenase-deficient gastrointestinal stromal tumors. (PMID:23060355)
• Data indicate that SDHB-deficiency was tightly associated with overexpression of IGF1R protein and transcript, and Biallelic inactivation of the SDHA gene was identified in 5 of 11 SDHB-negative gastrointestinal stromal tumors. (PMID:23109135)
• Studies indicate that an array of tumor syndromes caused by complex II-associated mutations in genes SDHA, SDHB, SDHC, SDHD, SDHAF1 and SDHAF2 have been identified over a decade. (PMID:23174333)
• SDHA immunohistochemistry on gastrointestinal stromal tumors can identify the presence of an SDHA germline mutation. (PMID:23174939)
• SDHA-negative gastrointestinal stromal tumors comprise approximately 30% of SDHB-negative/SDH-deficient gastrointestinal stromal tumors, and SDHA loss generally correlates with SDHA mutations. (PMID:23282968)
• Studies indicate that mutations in the mitochondrial complex II structural subunit genes SDHB, SDHC and SDHD and the regulatory subunit gene SDHAF2 in many paraganglioma families. (PMID:23291190)
• Studies indicate that the flavinylation factor Sdh5 (SDHAF2) provided insight into the possible mechanism associated with Sdh1 (SDHA) flavinylation. (PMID:23380393)
• Overall, 9 of the 34 patients with KIT/PDGFRA wild-type GIST carried mutations in one of the four subunits of the SDH complex (six patients in SDHA, two in SDHB, one in SDHC (PMID:23612575)
• In the paraganglioma of the proband, in addition to the germline mutation, a somatic mutation was observed (c.1865G>A, p.Trp622*). (PMID:23633203)
• SDH deficiency may promote tumorigenesis through accumulation of succinate and inhibition of dioxygenase enzymes. Inhibition of TET activity may, in turn, alter global DNA methylation and gene expression in SDH-deficient tumors. (PMID:23743927)
• A significant subset of bladder paragangliomas is SDH deficient (PMID:23797725)
• Electron transport complex-II and manganese superoxide dismutase (MnSOD) enzyme activities were decreased in obese compared with non-obese pregnant women. (PMID:23956348)
• Data indicate that SDH5 is protected from mitochondrial LON protease (LONM)-mediated degradation in mitochondria by its stable interaction with SDHA, a state that is dysregulated in hereditary paraganglioma 2 (PGL2). (PMID:24414418)
• Three novel mutations in SDHA were found in patients presenting Leigh syndrome (LS) and/or leukodystrophy. (PMID:24781757)
• our findings provide further evidence that patients with KIT/PDGFRA wild-type SDH-deficient GIST harboring SDHA mutations experience good survival outcomes (PMID:25188872)
• This study strengthens the etiological association of SDH genes with pituitary neoplasia, renal tumorigenesis, and gastric gastrointestinal stromal tumors. Also, pancreatic neuroendocrine tumor falls within the SDH-related tumor spectrum. (PMID:26259135)
• According to international guidelines, SDHB, SDHC, and SDHD genetic testing were performed in this patient, but not SDHA, which would have been prescribed only after surgery, in case of SDHA negative immunohistochemistry (PMID:26490314)
• As a similar defect of succinate dehydrogenase is apparent in patient cell-derived cardiomyocytes, the authors conclude that these defects represent a molecular basis for the cardiac pathology in Barth syndrome. (PMID:26697888)
• Combined blockade of CDK and SDH, both genetically and pharmaceutically, showed synergy and resulted in inhibited proliferation, migration, invasion and migration in A2780 cells Cyclin E-driven OvCa cells appeared addicted to glucose metabolism via TCA. Combined CDKi with modalities targeting TCA, like SDHA inhibition showed promising effects for this genotype. (PMID:26826064)
• For classification, tumors were characterized by SDHA, B, C, or D (SDHX) mutations and other genetic and epigenetic alterations, including presence of mutations in germline (PMID:27011036)
• FAD interacts noncovalently with SDHA in the absence of SDH5 (PMID:27296776)
• SDH-deficient gastrointestinal stromal tumors (GISTs) account for approximately 8% of gastric GISTs and are associated with a high rate of distant metastasis, regardless of conventional risk category. (PMID:27340750)
• We found that microRNA 31 (miR-31) suppressed succinate dehydrogenase complex subunit A (SDHA) expression, vital for mitochondrial electron transport chain (ETC) complex II (PMID:27346679)
• data show that SDHA flavination is independent of SDHAF2 in breast cancer cells, employing an alternative mechanism. (PMID:27587393)
• This is only the second report supporting the dominant nature of the SDHA c.1351C>T (p.Arg451Cys) mutation being causative for an autosomal dominantly inherited mitochondrial metabolic disorder expanding the phenotypic presentation to an earlier onset of disease with additional cardiac involvement. (PMID:27683074)
• Data suggest that succinate dehydrogenases SDHA and SDHB immunohistochemistry should be interpreted with caution, due to possible false-positive or false-negative results, and ideally in the setting of quality assurance provided by molecular testing. (PMID:28179334)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sdha	ENSDARG00000016721
mus_musculus	Sdha	ENSMUSG00000021577
rattus_norvegicus	Sdha	ENSRNOG00000013331
drosophila_melanogaster	SdhA	FBGN0261439
caenorhabditis_elegans		WBGENE00015391
caenorhabditis_elegans	sdha-2	WBGENE00016392

Protein

Protein identifiers

Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial — P31040 (reviewed: P31040)

Alternative names: Flavoprotein subunit of complex II, Malate dehydrogenase [quinone] flavoprotein subunit

All UniProt accessions (5): P31040, D6REB7, D6RFM5, H0Y8S2, H0Y8X1

UniProt curated annotations — full annotation on UniProt →

Function. Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). SDH also oxidizes malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate. Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerized into keto-oxaloacetate. Can act as a tumor suppressor.

Subunit / interactions. Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD. Interacts with SDHAF2/SDH5; interaction is required for FAD attachment. Interacts with TRAP1. Interacts with LACC1.

Subcellular location. Mitochondrion inner membrane.

Post-translational modifications. Phosphorylation at Tyr-215 is important for efficient electron transfer in complex II and the prevention of ROS generation. Acetylated. Deacetylated by SIRT3.

Disease relevance. Mitochondrial complex II deficiency, nuclear type 1 (MC2DN1) [MIM:252011] A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. MC2DN1 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Leigh syndrome (LS) [MIM:256000] An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, dilated, 1GG (CMD1GG) [MIM:613642] A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. The disease is caused by variants affecting the gene represented in this entry. Pheochromocytoma/paraganglioma syndrome 5 (PPGL5) [MIM:614165] 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. PPGL5 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Neurodegeneration with ataxia and late-onset optic atrophy (NDAXOA) [MIM:619259] An autosomal dominant disorder characterized by slowly progressive cerebellar and gait ataxia, optic atrophy, and myopathy or myalgia. Additional features can include cardiomyopathy, psychiatric disturbances, and peripheral sensory impairment. Disease onset is usually in mid-adulthood. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Enol-oxaloacetate inhibits the succinate dehydrogenase activity.

Pathway. Carbohydrate metabolism; tricarboxylic acid cycle; fumarate from succinate (eukaryal route): step 1/1.

Similarity. Belongs to the FAD-dependent oxidoreductase 2 family. FRD/SDH subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P31040-1	1	yes
P31040-2	2
P31040-3	3

RefSeq proteins (3): NP_001281261, NP_001317687, NP_004159* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003952	FRD_SDH_FAD_BS	Binding_site
IPR003953	FAD-dep_OxRdtase_2_FAD-bd	Domain
IPR011281	Succ_DH_flav_su_fwd	Family
IPR014006	Succ_Dhase_FrdA_Gneg	Family
IPR015939	Fum_Rdtase/Succ_DH_flav-like_C	Domain
IPR027477	Succ_DH/fumarate_Rdtase_cat_sf	Homologous_superfamily
IPR030664	SdhA/FrdA/AprA	Family
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR037099	Fum_R/Succ_DH_flav-like_C_sf	Homologous_superfamily

Pfam: PF00890, PF02910

Catalyzed reactions (Rhea), 3 shown:

• a ubiquinone + succinate = a ubiquinol + fumarate (RHEA:13713)
• (R)-malate + a quinone = enol-oxaloacetate + a quinol (RHEA:79827)
• (S)-malate + a quinone = enol-oxaloacetate + a quinol (RHEA:79831)

UniProt features (131 total): modified residue 28, strand 26, helix 23, binding site 17, sequence variant 14, turn 11, sequence conflict 7, splice variant 2, transit peptide 1, chain 1, active site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8DYE	X-RAY DIFFRACTION	1.44
8DYD	X-RAY DIFFRACTION	1.52
6VAX	X-RAY DIFFRACTION	2.59
9KC4	ELECTRON MICROSCOPY	2.65
8GS8	ELECTRON MICROSCOPY	2.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31040-F1	94.06	0.92

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 (1): 340 (proton acceptor)

Ligand- & substrate-binding residues (17): 221; 275; 296; 340; 407; 440; 451; 454; 456; 457; 69; 72 …

Post-translational modifications (28): 99, 167, 179, 179, 182, 215, 250, 250, 335, 335, 480, 485, 485, 498, 498, 517, 538, 538, 541, 547 …

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-611105	Respiratory electron transport
R-HSA-71403	Citric acid cycle (TCA cycle)
R-HSA-9854311	Maturation of TCA enzymes and regulation of TCA cycle
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism

MSigDB gene sets: 578 (showing top): MORF_MTA1, MODY_HIPPOCAMPUS_POSTNATAL, TGCGCANK_UNKNOWN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, MORF_HDAC1, MORF_RAD21, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MORF_HDAC2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_4NM_DN, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY

GO Biological Process (7): tricarboxylic acid cycle (GO:0006099), succinate metabolic process (GO:0006105), mitochondrial electron transport, succinate to ubiquinone (GO:0006121), nervous system development (GO:0007399), respiratory electron transport chain (GO:0022904), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), electron transport chain (GO:0022900)

GO Molecular Function (6): succinate dehydrogenase (quinone) activity (GO:0008177), electron transfer activity (GO:0009055), flavin adenine dinucleotide binding (GO:0050660), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-CH group of donors (GO:0016627)

GO Cellular Component (6): nucleolus (GO:0005730), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), respiratory chain complex II (succinate dehydrogenase) (GO:0045273), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	2
Citric acid cycle (TCA cycle)	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
aerobic respiration	1
primary metabolic process	1
dicarboxylic acid metabolic process	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
system development	1
electron transport chain	1
cellular respiration	1
oxidative phosphorylation	1
proton motive force-driven ATP synthesis	1
generation of precursor metabolites and energy	1
succinate dehydrogenase activity	1
oxidoreductase activity, acting on the CH-CH group of donors, quinone or related compound as acceptor	1
molecular_function	1
nucleotide binding	1
anion binding	1
binding	1
catalytic activity	1
oxidoreductase activity	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1
membrane protein complex	1
respiratory chain complex	1
oxidoreductase complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

5428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDHA	SDHD	O14521	999
SDHA	SDHB	P21912	999
SDHA	SDHC	Q99643	999
SDHA	SDHAF2	Q9NX18	999
SDHA	F5H5T6	F5H5T6	997
SDHA	SDHAF1	A6NFY7	996
SDHA	UQCRC2	P22695	914
SDHA	NDUFA9	Q16795	886
SDHA	MT-CYB	P00156	866
SDHA	ATP5F1B	P06576	842
SDHA	NDUFS8	O00217	835
SDHA	NDUFS1	P28331	827
SDHA	COX4I1	P13073	826
SDHA	ATP5F1A	P25705	826
SDHA	NDUFS3	O75489	819

IntAct

191 interactions, top by confidence:

A	B	Type	Score
SDHB	SDHA	psi-mi:“MI:0914”(association)	0.820
SDHA	SDHB	psi-mi:“MI:0914”(association)	0.820
SDHA	SDHB	psi-mi:“MI:0915”(physical association)	0.820
SDHB	SDHA	psi-mi:“MI:0915”(physical association)	0.820
SDHB	SDHAF1	psi-mi:“MI:0914”(association)	0.790
SDHAF2	SDHA	psi-mi:“MI:0915”(physical association)	0.740
SDHA	CFTR	psi-mi:“MI:0915”(physical association)	0.740
SIRT3	HSPD1	psi-mi:“MI:0914”(association)	0.730
ATP6V0A2	ATP6AP2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
nef	ACOT8	psi-mi:“MI:0914”(association)	0.710
PTPN3	MCC	psi-mi:“MI:0914”(association)	0.660
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
RPS6	IPO7	psi-mi:“MI:0914”(association)	0.530
PTPN3	SDHA	psi-mi:“MI:0915”(physical association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (522): SDHA (Affinity Capture-RNA), APOA1BP (Co-fractionation), ATP1B1 (Co-fractionation), ATP5F1 (Co-fractionation), CPNE1 (Co-fractionation), CPNE3 (Co-fractionation), CYC1 (Co-fractionation), DLD (Co-fractionation), DNAJA3 (Co-fractionation), HSPA9 (Co-fractionation), HSPB1 (Co-fractionation), MDH2 (Co-fractionation), MTCH1 (Co-fractionation), NDUFA2 (Co-fractionation), NDUFV1 (Co-fractionation)

ESM2 similar proteins: G4V4G6, O82663, P00363, P08065, P0AC41, P0AC42, P0AC43, P10902, P20922, P31038, P31039, P31040, P44894, P47052, P51054, P64175, P9WN90, Q00711, Q09508, Q0QF01, Q0QF17, Q1RHB9, Q28ED0, Q33862, Q4UJM1, Q51363, Q59661, Q5R616, Q68XN9, Q6PA58, Q6ZDY8, Q7M827, Q7ZVF3, Q801S2, Q8HXW3, Q8K2B3, Q8WSR3, Q8XWM7, Q8Z4K0, Q8ZD80

Diamond homologs: A0A1S3YEG8, A0A1S4BJT3, D9PU00, G4V4G6, O66973, O82663, P00363, P0AC41, P0AC42, P0AC43, P10902, P17412, P20922, P31038, P31039, P31040, P38032, P44894, P47052, P51054, P64175, P65500, P74562, P9WJJ8, P9WJJ9, P9WN90, P9WN91, Q00711, Q09508, Q0QF01, Q0QF17, Q1RHB9, Q28ED0, Q33862, Q49617, Q4UJM1, Q51363, Q59661, Q59767, Q5R616

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SDHA	“form complex”	“Succinate dehydrogenase-Mitochondrial respiratory chain complex II”	binding
SRC	“up-regulates activity”	SDHA	phosphorylation
FGR	unknown	SDHA	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 196 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial unfolded protein response (UPRmt)	5	22.6×	8e-04
Maturation of TCA enzymes and regulation of TCA cycle	5	21.5×	8e-04
SPOP-mediated proteasomal degradation of PD-L1(CD274)	6	10.3×	5e-03
Neddylation	14	5.0×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
SMAD protein signal transduction	5	21.3×	1e-03
intrinsic apoptotic signaling pathway	8	16.7×	4e-05
positive regulation of miRNA transcription	8	13.5×	1e-04
cellular response to estradiol stimulus	5	11.9×	6e-03
cellular response to epidermal growth factor stimulus	6	11.1×	3e-03
negative regulation of cell cycle	6	10.1×	4e-03
hematopoietic progenitor cell differentiation	6	8.3×	9e-03
transforming growth factor beta receptor signaling pathway	8	7.4×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — CHRCC, HCC, LGGNOS.

Clinical variants and AI predictions

ClinVar

3323 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	186
Likely pathogenic	97
Uncertain significance	1619
Likely benign	743
Benign	67

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1067845	NM_004168.4(SDHA):c.457-2A>G	Pathogenic
1069259	NM_004168.4(SDHA):c.1032_1033del (p.Arg345fs)	Pathogenic
1070947	NM_004168.4(SDHA):c.1012del (p.Ala338fs)	Pathogenic
1072916	NM_004168.4(SDHA):c.79C>T (p.Gln27Ter)	Pathogenic
1075636	NM_004168.4(SDHA):c.124_125dup (p.Ala43fs)	Pathogenic
1323568	NM_004168.4(SDHA):c.1075_1078del (p.Pro359fs)	Pathogenic
1325697	NM_004168.4(SDHA):c.526C>T (p.Gln176Ter)	Pathogenic
1354535	NM_004168.4(SDHA):c.392_396dup (p.Leu133fs)	Pathogenic
1357420	NM_004168.4(SDHA):c.1245dup (p.Asn416fs)	Pathogenic
1370664	NM_004168.4(SDHA):c.467dup (p.Tyr156Ter)	Pathogenic
1389565	NM_004168.4(SDHA):c.1764dup (p.Arg589fs)	Pathogenic
1401495	NM_004168.4(SDHA):c.1035del (p.Ser346fs)	Pathogenic
1405170	NM_004168.4(SDHA):c.1755_1759del (p.Lys586fs)	Pathogenic
1408872	NM_004168.4(SDHA):c.3G>T (p.Met1Ile)	Pathogenic
1425164	NM_004168.4(SDHA):c.1558C>T (p.Gln520Ter)	Pathogenic
1442909	NM_004168.4(SDHA):c.1470_1473dup (p.Ser492fs)	Pathogenic
1451165	NM_004168.4(SDHA):c.23C>A (p.Ser8Ter)	Pathogenic
1453363	NM_004168.4(SDHA):c.633T>G (p.Tyr211Ter)	Pathogenic
1453517	NM_004168.4(SDHA):c.1743_1744del (p.Ala582fs)	Pathogenic
1455102	NM_004168.4(SDHA):c.3G>C (p.Met1Ile)	Pathogenic
1456663	NM_004168.4(SDHA):c.65G>A (p.Trp22Ter)	Pathogenic
1458523	NM_004168.4(SDHA):c.1658_1661del (p.Asp553fs)	Pathogenic
1458794	NM_004168.4(SDHA):c.447del (p.Val150fs)	Pathogenic
1709506	NM_004168.4(SDHA):c.1283_1298del (p.Gln428fs)	Pathogenic
1750996	NM_004168.4(SDHA):c.5dup (p.Val4fs)	Pathogenic
1764097	NM_004168.4(SDHA):c.862C>T (p.Gln288Ter)	Pathogenic
1769163	NM_004168.4(SDHA):c.1293del (p.Ile431fs)	Pathogenic
1770427	NM_004168.4(SDHA):c.1344dup (p.Ala449fs)	Pathogenic
1772107	NM_004168.4(SDHA):c.1414G>T (p.Glu472Ter)	Pathogenic
1773839	NM_004168.4(SDHA):c.1494_1516del (p.Lys498fs)	Pathogenic

SpliceAI

2914 predictions. Top by Δscore:

Variant	Effect	Δscore
5:223471:T:TA	acceptor_gain	1.0000
5:223480:A:AG	acceptor_gain	1.0000
5:223480:AGT:A	acceptor_gain	1.0000
5:223481:G:GA	acceptor_gain	1.0000
5:223481:GT:G	acceptor_gain	1.0000
5:223481:GTG:G	acceptor_gain	1.0000
5:223564:ATTCC:A	donor_gain	1.0000
5:223565:TTCC:T	donor_gain	1.0000
5:223567:CCG:C	donor_loss	1.0000
5:223568:CGTA:C	donor_loss	1.0000
5:223569:G:GG	donor_gain	1.0000
5:225873:T:G	acceptor_gain	1.0000
5:225880:C:G	acceptor_gain	1.0000
5:225881:A:AG	acceptor_gain	1.0000
5:225882:G:GA	acceptor_gain	1.0000
5:225882:GCT:G	acceptor_gain	1.0000
5:225882:GCTA:G	acceptor_gain	1.0000
5:226043:GAAGG:G	donor_gain	1.0000
5:226044:AAGGG:A	donor_loss	1.0000
5:226046:GG:G	donor_gain	1.0000
5:226047:GG:G	donor_gain	1.0000
5:226048:G:GA	donor_loss	1.0000
5:226049:T:A	donor_loss	1.0000
5:228183:A:AC	acceptor_loss	1.0000
5:228183:A:AG	acceptor_gain	1.0000
5:228184:G:GC	acceptor_gain	1.0000
5:228184:GT:G	acceptor_gain	1.0000
5:228184:GTC:G	acceptor_gain	1.0000
5:228184:GTCT:G	acceptor_gain	1.0000
5:228184:GTCTC:G	acceptor_gain	1.0000

AlphaMissense

4299 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:224489:T:C	F94L	1.000
5:224491:T:A	F94L	1.000
5:224491:T:G	F94L	1.000
5:224493:C:A	P95H	1.000
5:224499:G:T	R97M	1.000
5:224521:G:C	Q104H	1.000
5:224521:G:T	Q104H	1.000
5:225419:G:A	G105R	1.000
5:225419:G:C	G105R	1.000
5:225479:G:C	D125H	1.000
5:225480:A:C	D125A	1.000
5:225480:A:T	D125V	1.000
5:225491:G:C	G129R	1.000
5:225492:G:A	G129D	1.000
5:225500:T:A	W132R	1.000
5:225500:T:C	W132R	1.000
5:225506:G:T	G134W	1.000
5:225937:C:A	R171S	1.000
5:225947:G:A	G174D	1.000
5:225950:G:A	G175E	1.000
5:225993:C:G	C189W	1.000
5:225996:C:G	C190W	1.000
5:226006:G:C	D194H	1.000
5:226010:G:C	R195P	1.000
5:226015:G:C	G197R	1.000
5:226016:G:A	G197D	1.000
5:226025:T:C	L200P	1.000
5:228321:T:A	V253D	1.000
5:230903:C:G	C266W	1.000
5:230926:G:A	G274D	1.000

dbSNP variants (sampled 300 via entrez): RS1000084393 (5:233762 T>G), RS1000171154 (5:223932 A>G), RS1000198147 (5:223655 T>C), RS1000324545 (5:218527 C>G,T), RS1000414475 (5:265274 T>C), RS1000469692 (5:220865 T>G), RS1000771219 (5:253724 T>G), RS1000924994 (5:238400 CA>C), RS1000955613 (5:238157 T>A), RS1001142173 (5:242976 T>G), RS1001218185 (5:222298 C>G), RS1001329614 (5:217726 G>A), RS1001418221 (5:263829 C>T), RS1001450986 (5:217396 GGAT>G), RS1001531356 (5:246823 A>G)

Disease associations

OMIM: gene MIM:600857 | disease phenotypes: MIM:614165, MIM:252011, MIM:613642, MIM:619259, MIM:256000, MIM:168000, MIM:606764, MIM:604287, MIM:163800, MIM:171300, MIM:114480, MIM:115310, MIM:171400, MIM:619681

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex II deficiency, nuclear type 1	Definitive	Autosomal recessive
pheochromocytoma/paraganglioma syndrome 5	Definitive	Autosomal dominant
hereditary pheochromocytoma-paraganglioma	Definitive	Autosomal dominant
neurodegeneration with ataxia and late-onset optic atrophy	Strong	Autosomal dominant
Leigh syndrome	Moderate	Autosomal recessive
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
Leigh syndrome with leukodystrophy	Supportive	Autosomal recessive
mitochondrial complex II deficiency	Supportive	Autosomal recessive
gastrointestinal stromal tumor	Supportive	Autosomal dominant
dilated cardiomyopathy 1GG	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (4)

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

Disease	Classification	Inheritance
hereditary pheochromocytoma-paraganglioma	Definitive	AD
Leigh syndrome	Moderate	AR
mitochondrial disease	Definitive	AR
mitochondrial disease	Limited	AD

Mondo (34): pheochromocytoma/paraganglioma syndrome 5 (MONDO:0013602), hereditary neoplastic syndrome (MONDO:0015356), mitochondrial complex II deficiency, nuclear type 1 (MONDO:0100294), dilated cardiomyopathy 1GG (MONDO:0013339), neurodegeneration with ataxia and late-onset optic atrophy (MONDO:0031006), Leigh syndrome (MONDO:0009723), hereditary pheochromocytoma-paraganglioma (MONDO:0017366), gastrointestinal stromal tumor (MONDO:0011719), brain neoplasm (MONDO:0021211), intellectual disability (MONDO:0001071), rhabdomyosarcoma (MONDO:0005212), Carney triad (MONDO:0011424), pilocytic astrocytoma (MONDO:0016691), skeletal muscle disorder (MONDO:0020120), hereditary renal cell carcinoma (MONDO:0003008)

Orphanet (18): Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary pheochromocytoma-paraganglioma (Orphanet:29072), Isolated succinate-CoQ reductase deficiency (Orphanet:3208), Familial isolated dilated cardiomyopathy (Orphanet:154), Leigh syndrome (Orphanet:506), Gastrointestinal stromal tumor (Orphanet:44890), Carney triad (Orphanet:139411), Pilocytic astrocytoma (Orphanet:251612), Rhabdomyosarcoma (Orphanet:780), Skeletal muscle disease (Orphanet:98472), Hereditary sick sinus syndrome (Orphanet:166282), B-lymphoblastic leukemia/lymphoma with hypodiploidy (Orphanet:585942), Hereditary breast cancer (Orphanet:227535), Opsoclonus-myoclonus syndrome (Orphanet:1183), Dilated cardiomyopathy (Orphanet:217604)

HPO phenotypes

188 total (30 of 188 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000093	Proteinuria
HP:0000096	Glomerular sclerosis
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000478	Abnormality of the eye
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000526	Aniridia
HP:0000544	External ophthalmoplegia
HP:0000580	Pigmentary retinopathy
HP:0000602	Ophthalmoplegia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus
HP:0000648	Optic atrophy
HP:0000651	Diplopia
HP:0000716	Depression
HP:0000726	Dementia
HP:0000737	Irritability
HP:0000740	Episodic paroxysmal anxiety
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000969	Edema
HP:0000980	Pallor
HP:0000988	Skin rash

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90020028_1025	Hip circumference adjusted for BMI	7.000000e-10
GCST90020028_1026	Hip circumference adjusted for BMI	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (15)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D046152	Gastrointestinal Stromal Tumors	C04.557.450.565.370; C06.301.371.308; C06.405.249.308
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D007888	Leigh Disease	C10.228.140.163.100.412; C16.320.565.189.412; C16.320.565.202.810.444; C18.452.132.100.412; C18.452.648.189.412; C18.452.648.202.810.444; C18.452.660.520
D018813	Multiple Endocrine Neoplasia Type 2a	C04.588.322.400.505; C04.651.600.505; C04.700.630.505; C16.320.700.630.505; C19.344.400.505
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D053578	Opsoclonus-Myoclonus Syndrome	C04.588.614.550.600; C04.730.856.596; C10.228.758.500; C10.292.562.831; C10.574.781.662; C10.597.350.500.500; C11.590.725
D010235	Paraganglioma	C04.557.465.625.650.700; C04.557.580.625.650.700
D010673	Pheochromocytoma	C04.557.465.625.650.700.725; C04.557.580.625.650.700.725
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
C562840	Breast Cancer, Familial (supp.)
C565803	Carney Triad (supp.)
C536851	Familial renal cell carcinoma (supp.)
C565375	Mitochondrial Complex II Deficiency (supp.)
C563513	Sick Sinus Syndrome 2, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5758 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 27,339 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL126	LINEZOLID	4	27,339

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.92	Kd	119.7	nM	CHEMBL3752910
6.92	ED50	119.7	nM	CHEMBL3752910
5.63	Kd	2365	nM	CHEMBL5653589
5.63	ED50	2365	nM	CHEMBL5653589
5.09	IC50	8190	nM	LINEZOLID

PubChem BioAssay actives

3 with measured affinity, of 8 total; 3 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	2149357: Binding affinity to human SDHA incubated for 45 mins by Kinobead based pull down assay	kd	0.1197	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149357: Binding affinity to human SDHA incubated for 45 mins by Kinobead based pull down assay	kd	2.3647	uM
Linezolid	1553386: Inhibition of SDH-A (unknown origin) by ELISA	ic50	8.1900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	decreases expression, decreases reaction, affects reaction, affects response to substance, affects expression	3
Benzo(a)pyrene	affects cotreatment, decreases expression, increases methylation	3
bisphenol F	affects cotreatment, decreases expression, increases expression	2
Resveratrol	decreases acetylation, decreases reaction, increases expression	2
Acetaminophen	affects cotreatment, affects expression, decreases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Atrazine	decreases expression, increases expression	2
Dexamethasone	affects cotreatment, decreases expression	2
Ozone	affects expression, affects cotreatment, decreases expression, increases abundance	2
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	2
ML-265	decreases expression, decreases reaction	1
bufotalin	increases expression	1
lasiocarpine	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
nobiletin	decreases reaction, decreases expression	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
2,6-dichloro-4-nitrophenol	decreases expression	1
ochratoxin A	decreases expression, decreases reaction	1
benzo(e)pyrene	increases methylation	1
acetyl methyl tetramethyl tetralin	affects cotreatment, decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
1-methyl-4-phenyl-2,3-dihydropyridinium	decreases expression	1
chromium hexavalent ion	decreases expression	1
U 0126	affects expression, affects reaction	1
K 7174	decreases expression	1
quinoxyfen	affects cotreatment, decreases expression	1
tofacitinib	increases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4350890	Binding	Inhibition of SDH-A (unknown origin) by ELISA	Incorporation of a chiral gem-disubstituted nitrogen heterocycle yields an oxazolidinone antibiotic with reduced mitochondrial toxicity. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1BF	Abcam HEK293 SDHA KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00171977	PHASE4	COMPLETED	Post-Marketing Clinical Study of Postoperative Adjuvant Therapy With Imatinib Mesylate in Patients With Gastrointestinal Stromal Tumors (GIST)
NCT00510354	PHASE4	COMPLETED	Treatment of Patients With Everolimus and Imatinib Mesylate Who Have Progressive Gastro Intestinal Stromal Tumors (GIST) and Are Resistant to Imatinib Mesylate
NCT00756509	PHASE4	COMPLETED	Treatment of Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors in First Line With Nilotinib
NCT00777504	PHASE4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT02800330	PHASE4	COMPLETED	The Effects of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib
NCT04825574	PHASE4	COMPLETED	Study for Patients Previously Treated in Avapritinib Clinical Trials
NCT00009906	PHASE3	TERMINATED	Comparison of Two Different Doses of STI571 in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
NCT00041197	PHASE3	COMPLETED	Imatinib Mesylate in Treating Patients With Primary Gastrointestinal Stromal Tumor That Has Been Completely Removed By Surgery
NCT00075218	PHASE3	COMPLETED	A Study To Assess The Safety And Efficacy Of SU11248 In Patients With Gastrointestinal Stromal Tumor(GIST)
NCT00103168	PHASE3	COMPLETED	Imatinib Mesylate or Observation Only in Treating Patients Who Have Undergone Surgery for Localized Gastrointestinal Stromal Tumor
NCT00293124	PHASE3	COMPLETED	Open-label Trial of GlivecWith Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumors
NCT00324987	PHASE3	TERMINATED	Imatinib Mesylate With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
NCT00372567	PHASE3	TERMINATED	Safety And Effectiveness Of Daily Dosing With Sunitinib Or Imatinib In Patients With Gastrointestinal Stromal Tumors
NCT00471328	PHASE3	COMPLETED	Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib
NCT00685828	PHASE3	UNKNOWN	Imatinib Mesylate in Treating Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumor
NCT00688766	PHASE3	TERMINATED	Study Evaluating IPI-504 in Patients With Gastrointestinal Stromal Tumors (GIST) Following Failure of at Least Imatinib and Sunitinib
NCT00751036	PHASE3	TERMINATED	Nilotinib 800 Mg And Imatinib 800 Mg For The Treatment Of Patients With Gastrointestinal Stromal Tumors (Gist) Refractory To Imatinib 400 Mg
NCT00785785	PHASE3	COMPLETED	A Study of Nilotinib Versus Imatinib in GIST Patients
NCT00812240	PHASE3	TERMINATED	Masitinib in First Line Treatment of Gastro-Intestinal Stromal Tumor (GIST)
NCT00956072	PHASE3	TERMINATED	Imatinib Mesylate With or Without Surgery in Treating Patients With Metastatic Gastrointestinal Stromal Tumor That is Responding to Imatinib Mesylate
NCT01031628	PHASE3	TERMINATED	Study of Dose Escalation Versus no Dose Escalation of Imatinib in Metastatic Gastrointestinal Stromal Tumors (GIST) Patients
NCT01151852	PHASE3	COMPLETED	Rechallenge of Imatinib in GIST Having no Effective Treatment: RIGHT
NCT01265810	PHASE3	COMPLETED	Caphosol in Oral Mucositis Due to Targeted Therapy
NCT01271712	PHASE3	COMPLETED	Study of Regorafenib as a 3rd-line or Beyond Treatment for Gastrointestinal Stromal Tumors (GIST)
NCT01289028	PHASE3	COMPLETED	Efficacy of Nilotinib in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Imatinib and Sunitinib.
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