SUCLG2

Summary

SUCLG2 (succinate-CoA ligase GDP-forming subunit beta, HGNC:11450) is a protein-coding gene on chromosome 3p14.1, encoding Succinate–CoA ligase [GDP-forming] subunit beta, mitochondrial (Q96I99). GTP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of GTP and thus represents the only step of substrate-level phosphorylation in the TCA.

This gene encodes a GTP-specific beta subunit of succinyl-CoA synthetase. Succinyl-CoA synthetase catalyzes the reversible reaction involving the formation of succinyl-CoA and succinate. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 5 and 12.

Source: NCBI Gene 8801 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 276 total
• Druggable target: yes
• MANE Select transcript: NM_003848

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11450
Approved symbol	SUCLG2
Name	succinate-CoA ligase GDP-forming subunit beta
Location	3p14.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172340
Ensembl biotype	protein_coding
OMIM	603922
Entrez	8801

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000307227, ENST00000460567, ENST00000492795, ENST00000493112, ENST00000906413, ENST00000951870, ENST00000951871, ENST00000951872

RefSeq mRNA: 2 — MANE Select: NM_003848 NM_001177599, NM_003848

CCDS: CCDS43104, CCDS54605

Canonical transcript exons

ENST00000307227 — 11 exons

Exon	Start	End
ENSE00001149369	67400731	67400851
ENSE00001175791	67495798	67495940
ENSE00001175802	67498134	67498295
ENSE00001175813	67508807	67508903
ENSE00001175836	67518247	67518336
ENSE00001175843	67520482	67520634
ENSE00001184428	67529087	67529186
ENSE00001184478	67528132	67528222
ENSE00001370595	67374719	67375859
ENSE00002402590	67609455	67609596
ENSE00002701843	67654503	67654612

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.7208 / max 322.9069, expressed in 1813 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42941	33.7208	1813

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic mucosa	UBERON:0000317	98.62	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.52	gold quality
rectum	UBERON:0001052	98.48	gold quality
jejunal mucosa	UBERON:0000399	98.33	gold quality
right lobe of liver	UBERON:0001114	97.89	gold quality
mucosa of transverse colon	UBERON:0004991	97.85	gold quality
duodenum	UBERON:0002114	97.62	gold quality
liver	UBERON:0002107	97.47	gold quality
jejunum	UBERON:0002115	97.39	gold quality
vastus lateralis	UBERON:0001379	97.13	gold quality
gastrocnemius	UBERON:0001388	96.96	gold quality
muscle of leg	UBERON:0001383	96.94	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.92	gold quality
quadriceps femoris	UBERON:0001377	96.90	gold quality
muscle organ	UBERON:0001630	96.88	gold quality
adult mammalian kidney	UBERON:0000082	96.67	gold quality
transverse colon	UBERON:0001157	96.61	gold quality
skeletal muscle tissue	UBERON:0001134	96.51	gold quality
renal medulla	UBERON:0000362	96.49	gold quality
biceps brachii	UBERON:0001507	96.40	gold quality
heart right ventricle	UBERON:0002080	96.39	gold quality
ileal mucosa	UBERON:0000331	96.29	gold quality
calcaneal tendon	UBERON:0003701	96.27	gold quality
deltoid	UBERON:0001476	96.10	gold quality
diaphragm	UBERON:0001103	96.09	gold quality
nephron tubule	UBERON:0001231	96.08	gold quality
muscle tissue	UBERON:0002385	96.00	gold quality
cardia of stomach	UBERON:0001162	95.98	gold quality
pylorus	UBERON:0001166	95.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	14.17
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

99 targeting SUCLG2, 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-1193	100.00	65.93	529
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478

Literature-anchored findings (GeneRIF, showing 6)

• Loss of SUCLG2 is associated with mitochondrial DNA depletion and results in mitochondrial depletion syndrome. (PMID:21295139)
• SUCLG2 has been identified as both a determinator of CSF amyloid beta-protein (1-42) levels and as attenuator of cognitive decline in Alzheimer’s disease. (PMID:25027320)
• The absence of SUCLA2 and SUCLG2 in human glia is in compliance with the presence of alternative pathways occurring in these cells, namely the GABA shunt and ketone body metabolism (PMID:25370487)
• SUCLG2 has a sensitivity of 75% and a specificity of 80% to distinguish follicular carcinoma from follicular adenoma (PMID:28709933)
• EGFR-upregulated LIFR promotes SUCLG2-dependent castration resistance and neuroendocrine differentiation of prostate cancer. (PMID:32963351)
• Succinyl-CoA Ligase Deficiency in Pro-inflammatory and Tissue-Invasive T Cells. (PMID:33264602)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	suclg2	ENSDARG00000044914
mus_musculus	Suclg2	ENSMUSG00000061838
rattus_norvegicus	Suclg2	ENSRNOG00000005686
drosophila_melanogaster	ScsbetaG	FBGN0029118
caenorhabditis_elegans		WBGENE00016844

Paralogs (1): SUCLA2 (ENSG00000136143)

Protein

Protein identifiers

Succinate–CoA ligase [GDP-forming] subunit beta, mitochondrial — Q96I99 (reviewed: Q96I99)

Alternative names: GTP-specific succinyl-CoA synthetase subunit beta, Itaconyl–CoA ligase [GDP-forming] subunit beta, Malyl–CoA ligase [GDP-forming] subunit beta, Succinyl-CoA synthetase beta-G chain

All UniProt accessions (3): Q96I99, E9PDQ8, H0Y852

UniProt curated annotations — full annotation on UniProt →

Function. GTP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit. Also able to act as a GTP-specific itaconyl- and malyl-CoA synthetase.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. The beta subunit determines specificity for GTP.

Subcellular location. Mitochondrion.

Tissue specificity. Mainly expressed in liver, kidney, heart, spleen and skeletal muscle. Also found in intestine and colon, and in low amounts in lung, brain, prostate, testis and ovary.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Pathway. Carbohydrate metabolism; tricarboxylic acid cycle; succinate from succinyl-CoA (ligase route): step 1/1.

Similarity. Belongs to the succinate/malate CoA ligase beta subunit family. GTP-specific subunit beta subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96I99-1	1	yes
Q96I99-2	2

RefSeq proteins (2): NP_001171070, NP_003839* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005809	Succ_CoA_ligase-like_bsu	Family
IPR005811	SUCC_ACL_C	Domain
IPR013650	ATP-grasp_succ-CoA_synth-type	Domain
IPR013815	ATP_grasp_subdomain_1	Homologous_superfamily
IPR016102	Succinyl-CoA_synth-like	Homologous_superfamily
IPR017866	Succ-CoA_synthase_bsu_CS	Conserved_site
IPR034722	Succ_CoA_betaG_euk	Family

Pfam: PF00549, PF08442

Enzyme classification (BRENDA):

• EC 6.2.1.4 — succinate-CoA ligase (GDP-forming) (BRENDA: 27 organisms, 37 substrates, 7 inhibitors, 27 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.009–0.63	9
SUCCINATE	0.39–5.1	6
COA	0.004–0.036	5
ATP	0.145–0.265	3
GDP	0.007	1
PHOSPHATE	2.26	1
SUCCINYL-COA	0.086	1

Catalyzed reactions (Rhea), 1 shown:

• GTP + succinate + CoA = succinyl-CoA + GDP + phosphate (RHEA:22120)

UniProt features (70 total): strand 18, helix 17, modified residue 14, binding site 7, turn 4, site 2, sequence variant 2, sequence conflict 2, transit peptide 1, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6WCV	X-RAY DIFFRACTION	1.52
7MSR	X-RAY DIFFRACTION	1.58
7MST	X-RAY DIFFRACTION	1.61
7MSS	X-RAY DIFFRACTION	1.75
8Z03	X-RAY DIFFRACTION	1.99
8Z02	X-RAY DIFFRACTION	2.32

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96I99-F1	89.38	0.77

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): 79 (important for substrate specificity); 147 (important for substrate specificity)

Ligand- & substrate-binding residues (7): 57; 90–92; 146; 243; 257; 308; 365–367

Post-translational modifications (14): 73, 78, 132, 139, 161, 200, 218, 227, 271, 291, 338, 347, 386, 423

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-71403	Citric acid cycle (TCA cycle)
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 211 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, CHX10_01, USF_C, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_SULFUR_COMPOUND_CATABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, MYCMAX_01, GOBP_AMIDE_METABOLIC_PROCESS, CAIRO_HEPATOBLASTOMA_DN

GO Biological Process (4): tricarboxylic acid cycle (GO:0006099), succinyl-CoA metabolic process (GO:0006104), succinate metabolic process (GO:0006105), succinyl-CoA catabolic process (GO:1901289)

GO Molecular Function (11): magnesium ion binding (GO:0000287), succinate-CoA ligase (GDP-forming) activity (GO:0004776), ATP binding (GO:0005524), GTP binding (GO:0005525), GDP binding (GO:0019003), protein-containing complex binding (GO:0044877), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), ligase activity (GO:0016874), metal ion binding (GO:0046872)

GO Cellular Component (7): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), plasma membrane (GO:0005886), succinate-CoA ligase complex (GO:0042709), succinate-CoA ligase complex (GDP-forming) (GO:0045244), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Metabolism of proteins	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine ribonucleoside triphosphate binding	2
guanyl ribonucleotide binding	2
binding	2
aerobic respiration	1
primary metabolic process	1
acyl-CoA metabolic process	1
dicarboxylic acid metabolic process	1
succinyl-CoA metabolic process	1
sulfur compound catabolic process	1
purine-containing compound catabolic process	1
nucleoside phosphate catabolic process	1
metal ion binding	1
succinate-CoA ligase activity	1
adenyl ribonucleotide binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
catalytic activity	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
tricarboxylic acid cycle heteromeric enzyme complex	1
succinate-CoA ligase complex	1
intracellular anatomical structure	1
cellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

3188 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SUCLG2	SUCLG1	P53597	996
SUCLG2	GNAQ	P50148	978
SUCLG2	GRK2	P25098	939
SUCLG2	PDC	P20941	934
SUCLG2	RGS11	O94810	899
SUCLG2	KCNJ3	P48549	892
SUCLG2	RGS7	P49802	891
SUCLG2	RGS6	P49758	891
SUCLG2	GNB1	P04697	875
SUCLG2	RGS12	O14924	863
SUCLG2	RGS21	Q2M5E4	861
SUCLG2	RGS17	Q9UGC6	853
SUCLG2	RGS8	P57771	853
SUCLG2	RGS20	O76081	853
SUCLG2	RGS13	O14921	852

IntAct

53 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SUCLG2	SUCLG1	psi-mi:“MI:0914”(association)	0.690
SUCLG1	SUCLG2	psi-mi:“MI:0407”(direct interaction)	0.690
HSCB	SUCLG2	psi-mi:“MI:0915”(physical association)	0.660
HSCB	NQO2	psi-mi:“MI:0914”(association)	0.550
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
HSCB	NDUFS8	psi-mi:“MI:0914”(association)	0.460
PAMR1	SUCLG2	psi-mi:“MI:0915”(physical association)	0.400
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
AK1	NBAS	psi-mi:“MI:0914”(association)	0.350
FASTKD3	VWA8	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
BCL2L14		psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
USP19		psi-mi:“MI:0914”(association)	0.350
DMWD	P4HA2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CTDP1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (2990): SUCLG2 (Affinity Capture-MS), ZNF146 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), ACADM (Co-fractionation), ATP6V1A (Co-fractionation), CCT3 (Co-fractionation), CCT6A (Co-fractionation), CTSD (Co-fractionation), HSP90B1 (Co-fractionation), IDH3A (Co-fractionation), LDHA (Co-fractionation), LDHAL6A (Co-fractionation), RPN1 (Co-fractionation), SUCLG1 (Co-fractionation)

ESM2 similar proteins: A0LZD4, A0RPE8, A1TW81, A1UQV9, A3PN13, A4WNM6, A4YKC6, A5E936, A5FHX8, A6GY30, A8EYY8, A8GNF5, A8GUV0, B1XRZ4, B1ZP17, B3E7B3, B3FHP0, B3Q760, B6JE33, B9KNB3, O82662, O94415, O97580, P53312, P53587, P53588, P53589, P53590, Q03184, Q13DR5, Q148D5, Q21CW8, Q2J3G9, Q2RV33, Q3IZ84, Q3MHX5, Q4R517, Q55AI5, Q6FYD1, Q6G1M1

Diamond homologs: A1AZH7, A1BE51, A1UQV9, A3PN13, A4SDL6, A4WNM6, A5FYZ9, A5VB78, A5VSQ3, A6U164, A6UDP2, A6WXE8, A7GRG6, A7HT39, A7X1L8, A8F1K7, A8FD73, A8GS29, A8GUV0, A9IZV3, A9M8R2, B0BXJ5, B0CIT0, B0T3D1, B1YIL7, B1ZP17, B2S880, B2UMH5, B3EFL3, B3EN95, B3FHP0, B3Q760, B3QPP2, B4RCH3, B4S612, B4SEH6, B6IP72, B8GYZ1, B9DPG0, B9EBC7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SUCLG2	“form complex”	“Succinyl-CoA GTP variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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.

GO biological processes:

GO term	Partners	Fold	FDR
DNA damage response	7	7.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	183
Likely benign	62
Benign	21

Top pathogenic / likely-pathogenic (0)

SpliceAI

3656 predictions. Top by Δscore:

Variant	Effect	Δscore
3:67375855:GGTTC:G	acceptor_gain	1.0000
3:67375856:GTTC:G	acceptor_gain	1.0000
3:67375856:GTTCC:G	acceptor_loss	1.0000
3:67375857:TTC:T	acceptor_gain	1.0000
3:67375857:TTCCT:T	acceptor_loss	1.0000
3:67375858:TC:T	acceptor_gain	1.0000
3:67375858:TCCTA:T	acceptor_loss	1.0000
3:67375859:CC:C	acceptor_gain	1.0000
3:67375859:CCTAG:C	acceptor_loss	1.0000
3:67375860:C:CA	acceptor_loss	1.0000
3:67375860:C:CC	acceptor_gain	1.0000
3:67375861:T:G	acceptor_loss	1.0000
3:67400726:CTCA:C	donor_loss	1.0000
3:67400728:CA:C	donor_loss	1.0000
3:67400729:A:AC	donor_gain	1.0000
3:67400729:A:AG	donor_loss	1.0000
3:67400730:C:A	donor_loss	1.0000
3:67400730:C:CC	donor_gain	1.0000
3:67400730:CCTT:C	donor_gain	1.0000
3:67400847:TCAAC:T	acceptor_gain	1.0000
3:67400848:CAAC:C	acceptor_gain	1.0000
3:67400848:CAACC:C	acceptor_gain	1.0000
3:67400849:AAC:A	acceptor_gain	1.0000
3:67400849:AACC:A	acceptor_gain	1.0000
3:67400850:AC:A	acceptor_gain	1.0000
3:67400850:ACC:A	acceptor_gain	1.0000
3:67400851:CC:C	acceptor_gain	1.0000
3:67400852:C:CC	acceptor_gain	1.0000
3:67400853:T:G	acceptor_loss	1.0000
3:67400859:C:CT	acceptor_gain	1.0000

AlphaMissense

2828 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:67495936:A:C	N308K	1.000
3:67495936:A:T	N308K	1.000
3:67529164:T:A	K83N	1.000
3:67529164:T:G	K83N	1.000
3:67375859:C:T	G395E	0.999
3:67400731:C:G	G395R	0.999
3:67400731:C:T	G395R	0.999
3:67400796:G:T	A373D	0.999
3:67400807:A:C	C369W	0.999
3:67400808:C:T	C369Y	0.999
3:67400823:C:T	G364D	0.999
3:67400825:A:C	F363L	0.999
3:67400825:A:T	F363L	0.999
3:67400827:A:G	F363L	0.999
3:67400829:A:T	I362K	0.999
3:67400831:A:C	N361K	0.999
3:67400831:A:T	N361K	0.999
3:67495870:G:C	F330L	0.999
3:67495870:G:T	F330L	0.999
3:67495872:A:G	F330L	0.999
3:67495907:T:A	D318V	0.999
3:67495925:A:G	L312P	0.999
3:67495925:A:T	L312H	0.999
3:67495928:C:T	G311E	0.999
3:67495929:C:A	G311W	0.999
3:67495929:C:G	G311R	0.999
3:67495929:C:T	G311R	0.999
3:67495934:C:A	G309V	0.999
3:67495934:C:T	G309D	0.999
3:67498138:G:C	C305W	0.999

dbSNP variants (sampled 300 via entrez): RS1000001843 (3:67589332 T>C), RS1000010525 (3:67516844 G>C), RS1000019904 (3:67443217 T>C), RS1000021579 (3:67478689 G>A,T), RS1000037474 (3:67387653 T>C), RS1000042277 (3:67587546 C>T), RS1000054739 (3:67401211 TC>T), RS1000058993 (3:67399833 T>C), RS1000069530 (3:67436873 A>C,G), RS1000070562 (3:67437548 T>A), RS1000074325 (3:67518543 A>G), RS1000075000 (3:67391280 T>C), RS1000075860 (3:67517203 T>C), RS1000089613 (3:67479881 T>C), RS1000099141 (3:67369689 G>A,T)

Disease associations

OMIM: gene MIM:603922 | disease phenotypes: MIM:245400

GenCC curated gene-disease

Mondo (1): mitochondrial DNA depletion syndrome 9 (MONDO:0009504)

Orphanet (1): Fatal infantile lactic acidosis with methylmalonic aciduria (Orphanet:17)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000817_187	Height	2.000000e-09
GCST001339_5	Corneal astigmatism	5.000000e-06
GCST001739_4	IgE levels	5.000000e-06
GCST002531_1	Cerebrospinal AB1-42 levels in Alzheimer’s disease dementia	3.000000e-12
GCST003098_21	Diabetic kidney disease	2.000000e-06
GCST004184_2	Lung function (FVC)	2.000000e-09
GCST005411_10	Thrombin-activatable fibrinolysis inhibitor activation peptide	1.000000e-08
GCST007429_109	Lung function (FVC)	7.000000e-15
GCST007432_123	FEV1	1.000000e-15
GCST008158_134	Body mass index	9.000000e-06
GCST008162_93	Hip circumference	6.000000e-06
GCST008180_9	Spontaneous preterm birth with premature rupture of membranes	2.000000e-06
GCST009391_675	Metabolite levels	2.000000e-06
GCST009733_103	Urinary metabolite levels in chronic kidney disease	7.000000e-15
GCST90002390_483	Mean corpuscular hemoglobin	4.000000e-12
GCST90002392_192	Mean corpuscular volume	1.000000e-15
GCST90002397_654	Mean spheric corpuscular volume	2.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004312	vital capacity
EFO:0004314	forced expiratory volume
EFO:0004340	body mass index
EFO:0006917	spontaneous preterm birth
EFO:0010356	lysophosphatidylcholine 14:0 measurement
EFO:0005116	urinary metabolite measurement
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C566885	Lactic Acidosis, Fatal Infantile (supp.)
C538134	Lactic acidosis congenital infantile (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067220 (SINGLE PROTEIN)

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

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
7.75	Kd	17.96	nM	CHEMBL5653589
7.27	ED50	54.02	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	2149525: Binding affinity to human SUCLG2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0180	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	8
Cadmium Chloride	increases expression, decreases expression, increases abundance	3
bisphenol A	affects expression, increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Arsenic Trioxide	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
acipimox	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
phenethyl isothiocyanate	affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases 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
CHEMBL5652567	Binding	Binding affinity to human SUCLG2 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

2 cell lines: 1 transformed cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3IN	Abcam HEK293T SUCLG2 KO	Transformed cell line	Female
CVCL_B4D7	WG3126	Finite cell line

Clinical trials (associated diseases)

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