SUCLG1 (succinate-CoA ligase GDP/ADP-forming subunit alpha)

Gene

• Entrez ID: 8802
• Gene name: Succinate-CoA ligase GDP/ADP-forming subunit alpha
• Gene symbol: SUCLG1
• Synonyms (NCBI Gene): GALPHA, MTDPS9, SUCLA1
• Chromosome: 2
• Chromosome location: 2p11.2
• Summary: This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are th

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs140626260	A>G	Pathogenic	Coding sequence variant, missense variant
rs143030960	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs267607097	C>G	Pathogenic	Coding sequence variant, missense variant
rs267607098	G>A	Pathogenic	Coding sequence variant, stop gained
rs267607099	G>C	Pathogenic	Coding sequence variant, missense variant
rs369610897	C>G	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs773748583	A>C	Likely-pathogenic	Missense variant, coding sequence variant
rs796052050	T>G	Likely-pathogenic	Coding sequence variant, missense variant
rs796052051	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs796052052	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs797046017	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1573369929	AC>TA	Pathogenic	Coding sequence variant, stop gained
rs1573374828	C>A	Pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT049513	hsa-miR-92a-3p	CLASH	23622248
MIRT042752	hsa-miR-339-5p	CLASH	23622248
MIRT042588	hsa-miR-423-3p	CLASH	23622248
MIRT2120531	hsa-miR-145	CLIP-seq
MIRT2120532	hsa-miR-199a-5p	CLIP-seq
MIRT2120533	hsa-miR-199b-5p	CLIP-seq
MIRT2120534	hsa-miR-2052	CLIP-seq
MIRT2120535	hsa-miR-2054	CLIP-seq
MIRT2120536	hsa-miR-2115	CLIP-seq
MIRT2120537	hsa-miR-217	CLIP-seq
MIRT2120538	hsa-miR-2276	CLIP-seq
MIRT2120539	hsa-miR-3607-3p	CLIP-seq
MIRT2120540	hsa-miR-3613-5p	CLIP-seq
MIRT2120541	hsa-miR-3686	CLIP-seq
MIRT2120542	hsa-miR-3920	CLIP-seq
MIRT2120543	hsa-miR-4418	CLIP-seq
MIRT2120544	hsa-miR-4436a	CLIP-seq
MIRT2120545	hsa-miR-4687-3p	CLIP-seq
MIRT2120546	hsa-miR-4696	CLIP-seq
MIRT2120547	hsa-miR-4760-3p	CLIP-seq
MIRT2120548	hsa-miR-509-3-5p	CLIP-seq
MIRT2120549	hsa-miR-509-5p	CLIP-seq
MIRT2120550	hsa-miR-593	CLIP-seq
MIRT2120551	hsa-miR-626	CLIP-seq
MIRT2120552	hsa-miR-647	CLIP-seq
MIRT2120532	hsa-miR-199a-5p	CLIP-seq
MIRT2120533	hsa-miR-199b-5p	CLIP-seq
MIRT2120537	hsa-miR-217	CLIP-seq
MIRT2120538	hsa-miR-2276	CLIP-seq
MIRT2342667	hsa-miR-4269	CLIP-seq
MIRT2120543	hsa-miR-4418	CLIP-seq
MIRT2342668	hsa-miR-4514	CLIP-seq
MIRT2342669	hsa-miR-4692	CLIP-seq
MIRT2120546	hsa-miR-4696	CLIP-seq
MIRT2342670	hsa-miR-4742-5p	CLIP-seq
MIRT2120548	hsa-miR-509-3-5p	CLIP-seq
MIRT2120549	hsa-miR-509-5p	CLIP-seq
MIRT2636466	hsa-miR-3138	CLIP-seq
MIRT2636467	hsa-miR-3618	CLIP-seq
MIRT2636468	hsa-miR-3692	CLIP-seq
MIRT2120542	hsa-miR-3920	CLIP-seq
MIRT2636469	hsa-miR-3929	CLIP-seq
MIRT2636470	hsa-miR-4328	CLIP-seq
MIRT2636471	hsa-miR-4419b	CLIP-seq
MIRT2636472	hsa-miR-4478	CLIP-seq
MIRT2636473	hsa-miR-4666-5p	CLIP-seq
MIRT2636474	hsa-miR-4731-5p	CLIP-seq
MIRT2636475	hsa-miR-640	CLIP-seq
MIRT2636476	hsa-miR-651	CLIP-seq
MIRT2636477	hsa-miR-934	CLIP-seq
MIRT2636466	hsa-miR-3138	CLIP-seq
MIRT2636467	hsa-miR-3618	CLIP-seq
MIRT2636468	hsa-miR-3692	CLIP-seq
MIRT2120542	hsa-miR-3920	CLIP-seq
MIRT2636469	hsa-miR-3929	CLIP-seq
MIRT2636471	hsa-miR-4419b	CLIP-seq
MIRT2636472	hsa-miR-4478	CLIP-seq
MIRT2636473	hsa-miR-4666-5p	CLIP-seq
MIRT2636474	hsa-miR-4731-5p	CLIP-seq
MIRT2636475	hsa-miR-640	CLIP-seq
MIRT2636477	hsa-miR-934	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003723	Function	RNA binding	HDA	22658674
GO:0003824	Function	Catalytic activity	IEA
GO:0004775	Function	Succinate-CoA ligase (ADP-forming) activity	IBA
GO:0004775	Function	Succinate-CoA ligase (ADP-forming) activity	IEA
GO:0004776	Function	Succinate-CoA ligase (GDP-forming) activity	IBA
GO:0004776	Function	Succinate-CoA ligase (GDP-forming) activity	IEA
GO:0005515	Function	Protein binding	IPI	28514442, 32627745, 33961781
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	NAS	32627745
GO:0005739	Component	Mitochondrion	TAS	9128182
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006099	Process	Tricarboxylic acid cycle	IBA
GO:0006099	Process	Tricarboxylic acid cycle	IEA
GO:0006099	Process	Tricarboxylic acid cycle	NAS	32627745
GO:0009361	Component	Succinate-CoA ligase complex (ADP-forming)	IBA
GO:0009361	Component	Succinate-CoA ligase complex (ADP-forming)	NAS	32627745
GO:0016874	Function	Ligase activity	IEA
GO:0045244	Component	Succinate-CoA ligase complex (GDP-forming)	IEA
GO:0045244	Component	Succinate-CoA ligase complex (GDP-forming)	IPI	32627745
GO:1901289	Process	Succinyl-CoA catabolic process	NAS	32627745

Other IDs

• MIM: 611224
• HGNC: 11449
• e!Ensembl: ENSG00000163541

Protein

• UniProt ID: P53597
• Protein name: Succinate--CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial (EC 6.2.1.4) (EC 6.2.1.5) (Succinyl-CoA synthetase subunit alpha) (SCS-alpha)
• Protein function: Succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of either ATP or GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The alpha subunit of
• PDB: 6G4Q, 6WCV, 7MSR, 7MSS, 7MST, 8Z02, 8Z03
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02629	CoA_binding	53 → 146	CoA binding domain	Domain
  PF00549	Ligase_CoA	199 → 324	CoA-ligase	Domain

• Sequence:

  MTATLAAAADIATMVSGSSGLAAARLLSRSFLLPQNGIRHCSYTASRQHLYVDKNTKIIC
  QGFTGKQGTFHSQQALEYGTKLVGGTTPGKGGQTHLGLPVFNTVKEAKEQTGATASVIYV
  PPPFAAAAINEAIEAEIPLVVCITEGIPQQDMVRVKHKLLRQEKTRLIGPNCPGVINPGE
  CKIGIMPGHIHKKGRIGIVSRSGTLTYEAVHQTTQVGLGQSLCVGIGGDPFNGTDFIDCL
  EIFLNDSATEGIILIGEIGGNAEENAAEFLKQHNSGPNSKPVVSFIAGLTAPPGRRMGHA
  GAIIAGGKGGAKEKISALQSAGVVVSMSPAQLGTTIYKEFEKRKML

• Sequence length: 346

Pathways

KEGG:

Citrate cycle (TCA cycle)
Propanoate metabolism
Metabolic pathways
Carbon metabolism

Reactome:

Citric acid cycle (TCA cycle)

Associated diseases

Evidence Score:

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

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Melanoma	Likely pathogenic	rs750388794	RCV005897391	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial DNA depletion syndrome 9	Pathogenic; Likely pathogenic	rs2104243406, rs1246050542, rs1672907018, rs2104245141, rs797046017, rs2468610727, rs2468618014, rs1478044147, rs2468620294, rs2468630662, rs1672524253, rs267607097, rs267607099, rs786205871, rs267607098, rs1308442327, rs1369567672, rs750388794, rs1573369925, rs1573374828, rs1573369929, rs570210229, rs369153479	RCV001822883 RCV001783829 RCV001902549 RCV002246751 RCV000193104 RCV003044523 RCV003131680 RCV003494635 RCV003602434 RCV003842831 RCV003863706 RCV000001040 RCV000001041 RCV000001042 RCV000001043 RCV000779337 RCV000779338 RCV000779336 RCV002246752 RCV000986785 RCV001009612 RCV001507287 RCV001387210	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ASTROCYTOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPLETION OF MITOCHONDRIAL DEOXYRIBONUCLEIC ACID	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEIGH SYNDROME	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial DNA depletion syndrome	Benign; Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STOMACH NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SUCLG1-related disorder	Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acidosis Lactic	Lactic acidosis	Pubtator	17668387	Associate	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	9257698	Associate	★☆☆☆☆ Found in Text Mining only
Aphasia	Aphasia	Pubtator	28087732	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	36308411	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Hypertrophic	Hypertrophic cardiomyopathy	Pubtator	10843907	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	28087732	Associate	★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	28035070		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	28035070	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	28035070		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	28035070		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	28035070	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hereditary Diffuse Gastric Cancer	Gastric Cancer	CTD_human_DG	21364753		★☆☆☆☆ Found in Text Mining only
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	BEFREE	26475597		★☆☆☆☆ Found in Text Mining only
Hypertrophic obstructive cardiomyopathy	Hypertrophic cardiomyopathy	BEFREE	26475597		★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh Syndrome	CLINGEN_DG	17668387, 19526370, 20197121, 20453710, 20693550, 25613900, 27484306, 29217198, 9128182		★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh syndrome	Pubtator	36675121	Associate	★☆☆☆☆ Found in Text Mining only
LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY	Leigh Syndrome	CLINGEN_DG	17668387, 19526370, 20197121, 20453710, 20693550, 25613900, 27484306, 29217198, 9128182		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome Due To Mitochondrial Complex II Deficiency	Leigh Syndrome	CLINGEN_DG	17668387, 19526370, 20197121, 20453710, 20693550, 25613900, 27484306, 29217198, 9128182		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex III Deficiency	Leigh Syndrome	CLINGEN_DG	17668387, 19526370, 20197121, 20453710, 20693550, 25613900, 27484306, 29217198, 9128182		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex IV Deficiency	Leigh Syndrome	CLINGEN_DG	17668387, 19526370, 20197121, 20453710, 20693550, 25613900, 27484306, 29217198, 9128182		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex V Deficiency	Leigh Syndrome	CLINGEN_DG	17668387, 19526370, 20197121, 20453710, 20693550, 25613900, 27484306, 29217198, 9128182		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	CTD_human_DG	21364753		★☆☆☆☆ Found in Text Mining only
McCune-Albright Syndrome	McCune-Albright Syndrome	BEFREE	17132542		★☆☆☆☆ Found in Text Mining only
Methylmalonic acidemia	Methylmalonic acidemia	Pubtator	27484306, 35361390	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	20453710	Associate	★☆☆☆☆ Found in Text Mining only
MITOCHONDRIAL DNA DEPLETION SYNDROME 9 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)	Mitochondrial DNA Depletion Syndrome	UNIPROT_DG	17668387, 19526370, 20453710, 20693550		★☆☆☆☆ Found in Text Mining only
MITOCHONDRIAL DNA DEPLETION SYNDROME 9 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)	Mitochondrial DNA Depletion Syndrome	ORPHANET_DG	19526370, 21639866		★☆☆☆☆ Found in Text Mining only
MITOCHONDRIAL DNA DEPLETION SYNDROME 9 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)	Mitochondrial DNA Depletion Syndrome	CLINVAR_DG	20453710, 21639866, 29217198		★☆☆☆☆ Found in Text Mining only
MITOCHONDRIAL DNA DEPLETION SYNDROME 9 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)	Mitochondrial DNA Depletion Syndrome	GENOMICS_ENGLAND_DG	27484306, 27604308		★☆☆☆☆ Found in Text Mining only
MITOCHONDRIAL DNA DEPLETION SYNDROME 9 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)	Mitochondrial DNA Depletion Syndrome	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial Encephalomyopathies	Mitochondrial encephalomyopathy	Pubtator	27484306	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Encephalomyopathies	Mitochondrial encephalomyopathy	BEFREE	29217198		★☆☆☆☆ Found in Text Mining only
Necrotizing encephalopathy, infantile subacute, of Leigh	Necrotizing encephalomyelopathy	CLINGEN_DG	17668387, 19526370, 20197121, 20453710, 20693550, 25613900, 27484306, 29217198, 9128182		★☆☆☆☆ Found in Text Mining only
Night blindness congenital stationary	Night blindness, congenital stationary	Pubtator	10702259	Associate	★☆☆☆☆ Found in Text Mining only
Night Blindness Congenital Stationary Autosomal Dominant 3	Night blindness, congenital stationary	Pubtator	10702259	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Diseases	Ovarian diseases	Pubtator	33454781	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Hyperstimulation Syndrome	Ovarian hyperstimulation syndrome	Pubtator	33454781	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	36593912	Associate	★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach Neoplasms	CTD_human_DG	21364753		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Uveal melanoma	Pubtator	21828154, 24551032, 25030020, 35352024	Associate	★☆☆☆☆ Found in Text Mining only
Visceral myopathy familial external ophthalmoplegia	Visceral neuropathy	Pubtator	19667227, 35762302	Associate	★☆☆☆☆ Found in Text Mining only