SUCLG2

succinate-CoA ligase GDP-forming subunit beta

Basic information

Region (hg38): 3:67360459-67654612

Links

ENSG00000172340 ∙ NCBI:8801 ∙ OMIM:603922 ∙ HGNC:11450 ∙ Uniprot:Q96I99 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SUCLG2 gene.

• not provided (74 variants)
• Inborn genetic diseases (18 variants)
• not specified (6 variants)
• Mitochondrial DNA depletion syndrome 9 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SUCLG2 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				10	2	12
missense			41	3	5	49
nonsense			1			1
start loss						0
frameshift			3		1	4
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	4	1	6
non coding				11	6	17
Total	0	0	46	24	14

Variants in SUCLG2

This is a list of pathogenic ClinVar variants found in the SUCLG2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-67360640-A-G			Uncertain significance (Jul 19, 2022)
3-67360675-G-A			Uncertain significance (Jan 10, 2024)
3-67360676-C-T			Uncertain significance (Jun 11, 2022)
3-67360679-C-T		not specified	Benign (Feb 01, 2024)
3-67360689-G-T			Likely benign (Jul 31, 2023)
3-67360707-A-T		SUCLG2-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)
3-67360719-T-C			Likely benign (Dec 12, 2023)
3-67360738-A-G			Uncertain significance (Nov 04, 2021)
3-67360742-A-G		not specified	Benign (Feb 01, 2024)
3-67360748-CT-C			Benign (Jan 22, 2024)
3-67375857-T-C		SUCLG2-related disorder	Benign (Jul 08, 2019)
3-67375866-G-A		SUCLG2-related disorder	Benign (Sep 12, 2019)
3-67375869-G-A		SUCLG2-related disorder	Likely benign (Oct 03, 2019)
3-67400711-G-A			Benign (Jan 22, 2024)
3-67400739-C-T			Uncertain significance (Jan 20, 2024)
3-67400752-G-C		not specified	Uncertain significance (May 06, 2022)
3-67400772-C-T			Likely benign (Aug 04, 2023)
3-67400773-G-A		not specified	Benign (Feb 01, 2024)
3-67400793-T-C			Uncertain significance (Jan 15, 2022)
3-67400794-T-G			Uncertain significance (Jan 04, 2024)
3-67400808-C-A		not specified	Uncertain significance (Aug 10, 2021)
3-67400815-C-T		not specified	Uncertain significance (Mar 20, 2023)
3-67400816-G-A			Likely benign (Jul 13, 2022)
3-67400818-T-C		not specified	Uncertain significance (Feb 03, 2022)
3-67400832-T-C		Mitochondrial DNA depletion syndrome 9 • not specified	Uncertain significance (Jan 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SUCLG2	protein_coding	protein_coding	ENST00000493112	11	294155

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.72e-14	0.0153	124715	1	78	124794	0.000317

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.488	244	223	1.09	0.0000114	2860
Missense in Polyphen		94	84.926	1.1069		1013
Synonymous	0.182	82	84.1	0.975	0.00000476	850
Loss of Function	-0.129	20	19.4	1.03	9.06e-7	251

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00105	0.00105
Ashkenazi Jewish	0.00	0.00
East Asian	0.000334	0.000334
Finnish	0.000186	0.000186
European (Non-Finnish)	0.000178	0.000168
Middle Eastern	0.000334	0.000334
South Asian	0.000643	0.000588
Other	0.000168	0.000165

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000255|HAMAP- Rule:MF_03221}.
• 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 ;miR-targeted genes in lymphocytes - TarBase;TCA Cycle and Deficiency of Pyruvate Dehydrogenase complex (PDHc);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: 0.498

Intolerance Scores

• loftool: 0.900
• rvis_EVS: 0.62
• rvis_percentile_EVS: 83.36

Haploinsufficiency Scores

• pHI: 0.232
• hipred: N
• hipred_score: 0.389
• ghis: 0.497

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.652

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Suclg2
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: tricarboxylic acid cycle;succinyl-CoA metabolic process;succinate metabolic process
• Cellular component: mitochondrion;mitochondrial matrix;plasma membrane;succinate-CoA ligase complex (GDP-forming)
• Molecular function: magnesium ion binding;succinate-CoA ligase (ADP-forming) activity;succinate-CoA ligase (GDP-forming) activity;protein binding;ATP binding;GTP binding;GDP binding;protein heterodimerization activity