SUCLG1

succinate-CoA ligase GDP/ADP-forming subunit alpha

Basic information

Region (hg38): 2:84423527-84460045

Links

ENSG00000163541 ∙ NCBI:8802 ∙ OMIM:611224 ∙ HGNC:11449 ∙ Uniprot:P53597 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial DNA depletion syndrome 9 (Strong), mode of inheritance: AR
• mitochondrial DNA depletion syndrome 9 (Definitive), mode of inheritance: AR
• mitochondrial DNA depletion syndrome 9 (Supportive), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Musculoskeletal; Neurologic	17668387; 19526370; 20693550; 21093335; 21639866

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SUCLG1 gene.

• Mitochondrial DNA depletion syndrome 9 (225 variants)
• not provided (77 variants)
• not specified (23 variants)
• Mitochondrial DNA depletion syndrome (22 variants)
• Inborn genetic diseases (13 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SUCLG1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	50	1	53
missense	3	4	97	2		106
nonsense	4	1				5
start loss			2			2
frameshift	2		1			3
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2				3
splice region			6	8		14
non coding			7	44	22	73
Total	10	7	109	96	23

Highest pathogenic variant AF is 0.0000263

Variants in SUCLG1

This is a list of pathogenic ClinVar variants found in the SUCLG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-84423528-T-C		Mitochondrial DNA depletion syndrome • Mitochondrial DNA depletion syndrome 9	Uncertain significance (Jun 14, 2016)
2-84423539-T-C		Mitochondrial DNA depletion syndrome 9 • Mitochondrial DNA depletion syndrome	Benign/Likely benign (Jun 14, 2018)
2-84423583-A-G		Mitochondrial DNA depletion syndrome 9 • Mitochondrial DNA depletion syndrome	Benign (Jun 23, 2018)
2-84423620-C-T		Mitochondrial DNA depletion syndrome 9	Uncertain significance (Jan 13, 2018)
2-84423691-C-G		Mitochondrial DNA depletion syndrome • Mitochondrial DNA depletion syndrome 9	Likely benign (Aug 17, 2018)
2-84423708-G-A		Mitochondrial DNA depletion syndrome 9 • Mitochondrial DNA depletion syndrome	Uncertain significance (Jun 14, 2016)
2-84423732-AT-A		Mitochondrial DNA depletion syndrome • Mitochondrial DNA depletion syndrome 9	Uncertain significance (Jun 14, 2016)
2-84423759-C-G		Mitochondrial DNA depletion syndrome • Mitochondrial DNA depletion syndrome 9	Uncertain significance (Jun 14, 2016)
2-84423761-C-G		Mitochondrial DNA depletion syndrome 9	Uncertain significance (Jun 27, 2022)
2-84423778-G-A		Mitochondrial DNA depletion syndrome 9	Likely benign (Aug 17, 2022)
2-84423786-A-C		Mitochondrial DNA depletion syndrome 9	Likely benign (Apr 24, 2023)
2-84423785-A-AAG		Mitochondrial DNA depletion syndrome 9	Likely benign (Apr 19, 2023)
2-84423790-A-T		Mitochondrial DNA depletion syndrome 9	Likely benign (Jul 29, 2023)
2-84423980-G-A			Benign (Jul 07, 2018)
2-84425409-G-T		Mitochondrial DNA depletion syndrome 9	Uncertain significance (Apr 27, 2023)
2-84425419-T-C		Mitochondrial DNA depletion syndrome 9	Uncertain significance (Jan 30, 2024)
2-84425424-C-T		Mitochondrial DNA depletion syndrome 9	Likely benign (Jan 25, 2024)
2-84425425-G-A		Mitochondrial DNA depletion syndrome 9	Uncertain significance (Feb 08, 2022)
2-84425439-T-C		Mitochondrial DNA depletion syndrome 9	Likely benign (Aug 17, 2023)
2-84425441-C-CA		-	no classification for the single variant (-)
2-84425456-C-T			Uncertain significance (Mar 18, 2021)
2-84425460-A-G		Mitochondrial DNA depletion syndrome 9	Likely benign (Nov 17, 2020)
2-84425470-C-T		Mitochondrial DNA depletion syndrome • Mitochondrial DNA depletion syndrome 9	Uncertain significance (Dec 22, 2023)
2-84425477-G-A			Uncertain significance (Dec 18, 2012)
2-84425480-C-G		Mitochondrial DNA depletion syndrome 9	Uncertain significance (Jul 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SUCLG1	protein_coding	protein_coding	ENST00000393868	9	36523

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000482	0.971	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.217	199	191	1.04	0.00000980	2229
Missense in Polyphen		73	79.789	0.91491		961
Synonymous	-0.132	72	70.6	1.02	0.00000384	708
Loss of Function	1.94	8	16.5	0.485	8.11e-7	200

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 the enzyme binds the substrates coenzyme A and phosphate, while succinate binding and specificity for either ATP or GTP is provided by different beta subunits. {ECO:0000255|HAMAP- Rule:MF_03222}.
• Disease: DISEASE: Mitochondrial DNA depletion syndrome 9 (MTDPS9) [MIM:245400]: A severe disorder due to mitochondrial dysfunction. It is characterized by infantile onset of hypotonia, lactic acidosis, severe psychomotor retardation, progressive neurologic deterioration, and excretion of methylmalonic acid. {ECO:0000269|PubMed:17668387, ECO:0000269|PubMed:19526370, ECO:0000269|PubMed:20453710, ECO:0000269|PubMed:20693550}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Propanoate metabolism - Homo sapiens (human);Valproic Acid Pathway, Pharmacodynamics;Pathway_PA165964473;Warburg Effect;The oncogenic action of Succinate;The oncogenic action of Fumarate;Pyruvate dehydrogenase deficiency (E3);Pyruvate dehydrogenase deficiency (E2);2-ketoglutarate dehydrogenase complex deficiency;Mitochondrial complex II deficiency;Fumarase deficiency;Congenital lactic acidosis;Citric Acid Cycle;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Amino Acid metabolism;TCA Cycle;Citrate cycle;Citric acid cycle (TCA cycle);Pyruvate metabolism and Citric Acid (TCA) cycle;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TCA cycle;TCA cycle;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle (Consensus)

Recessive Scores

• pRec: 0.535

Intolerance Scores

• loftool: 0.235
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.25

Haploinsufficiency Scores

• pHI: 0.163
• hipred: N
• hipred_score: 0.376
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Suclg1

Gene ontology

• Biological process: tricarboxylic acid cycle;succinyl-CoA metabolic process;succinate metabolic process;nucleoside diphosphate phosphorylation;nucleoside triphosphate biosynthetic process
• Cellular component: mitochondrion;mitochondrial matrix;cytosol;plasma membrane
• Molecular function: RNA binding;nucleoside diphosphate kinase activity;succinate-CoA ligase (ADP-forming) activity;cofactor binding