SUCLA2

succinate-CoA ligase ADP-forming subunit beta

Basic information

Region (hg38): 13:47745735-48037968

Previous symbols: [ "LINC00444" ]

Links

ENSG00000136143 ∙ NCBI:8803 ∙ OMIM:603921 ∙ HGNC:11448 ∙ Uniprot:Q9P2R7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (Strong), mode of inheritance: AR
• mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (Supportive), mode of inheritance: Mitochondrial
• Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial DNA depletion syndrome 5	AR	Audiologic/Otolaryngologic	Early recognition and treatment (eg, with cochlear implants) of hearing impairment, which may occur in the prelingual stage, may improve outcomes, including speech and language development	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic; Renal	15877282; 19015156; 17301081; 17287286; 19015156; 19666145; 20301762; 23010432
Features such as frequent infections and cardiomyopathy have been described in some individuals

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SUCLA2 gene.

• Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (255 variants)
• not provided (128 variants)
• not specified (29 variants)
• Inborn genetic diseases (21 variants)
• Mitochondrial DNA depletion syndrome (4 variants)
• SUCLA2-related condition (3 variants)
• Global developmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SUCLA2 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			3	45	2	50
missense		8	104	6	4	122
nonsense	3	1				4
start loss			1			1
frameshift	1	2				3
inframe indel			3			3
splice donor/acceptor (+/-2bp)	3	1				4
splice region			10	13		23
non coding		1	27	56	47	131
Total	7	13	138	107	53

Highest pathogenic variant AF is 0.00000658

Variants in SUCLA2

This is a list of pathogenic ClinVar variants found in the SUCLA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-47942656-T-TC		Mitochondrial DNA depletion syndrome	Uncertain significance (Jun 14, 2016)
13-47942710-G-C		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Benign (Jan 13, 2018)
13-47942710-G-T		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Benign (Jan 12, 2018)
13-47942790-A-C		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Benign (Jan 13, 2018)
13-47942903-T-C		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Jan 12, 2018)
13-47942936-T-C		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Jan 13, 2018)
13-47942937-A-C		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Jan 12, 2018)
13-47942940-C-G		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Jan 12, 2018)
13-47942980-T-C		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Jan 12, 2018)
13-47942991-G-A		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Jan 12, 2018)
13-47943022-G-C		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Jan 12, 2018)
13-47943040-G-T		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Jan 13, 2018)
13-47943043-T-C		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Benign (Jan 12, 2018)
13-47943052-T-A		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Jan 12, 2018)
13-47943071-TGAA-T		Mitochondrial DNA depletion syndrome	Uncertain significance (Jun 14, 2016)
13-47943119-G-A		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Jan 13, 2018)
13-47943151-G-A		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Jan 13, 2018)
13-47943154-A-G		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Benign (Jun 14, 2018)
13-47943166-A-G		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Benign (Jan 12, 2018)
13-47943176-T-C		Mitochondrial DNA depletion syndrome	Uncertain significance (Jun 14, 2016)
13-47943187-C-T		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Uncertain significance (Apr 27, 2017)
13-47943239-T-C			Likely benign (Jul 15, 2018)
13-47943336-A-C		Mitochondrial DNA depletion syndrome	Uncertain significance (Jun 14, 2016)
13-47943357-A-T		not specified	Benign (Feb 14, 2012)
13-47943398-C-T		Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	Likely benign (Jan 26, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SUCLA2	protein_coding	protein_coding	ENST00000378654	11	101504

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00235	0.997	125706	0	34	125740	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.02	206	252	0.819	0.0000122	3020
Missense in Polyphen		52	90.942	0.5718		1109
Synonymous	0.0386	86	86.5	0.995	0.00000438	887
Loss of Function	2.97	9	25.1	0.359	0.00000134	296

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: ATP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA (PubMed:15877282). 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 (By similarity). {ECO:0000255|HAMAP-Rule:MF_03220, ECO:0000269|PubMed:15877282}.
• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Propanoate metabolism - Homo sapiens (human);Valproic Acid Pathway, Pharmacodynamics;Pathway_PA165964473;fig-met-1-last-solution;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: 0.882

Intolerance Scores

• loftool: 0.743
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.54

Haploinsufficiency Scores

• pHI: 0.756
• hipred: N
• hipred_score: 0.426
• ghis: 0.612

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.937

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sucla2
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; embryo 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;succinyl-CoA pathway
• Cellular component: mitochondrion;mitochondrial matrix;myelin sheath;extracellular exosome
• Molecular function: magnesium ion binding;succinate-CoA ligase (ADP-forming) activity;protein binding;ATP binding