SUCLG2

protein-coding

succinate-CoA ligase GDP-forming subunit beta

Gene summary

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. [provided by RefSeq, Apr 2010]

MANE transcript

NM_003848.4

Inheritance

—

ClinVar variants

U:162B:36

Top phenotype

SUCLG2-related disorder

gnomAD constraint

pLI —, LoF o/e 1.03

Max pathogenic AF

—

Genomic locus

chr3:67,360,460-67,654,612

External References & Databases

Ensembl (ENSG00000172340)

Transcript & Mutation Effects

hg38 • Region Span ~294.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SUCLG2 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 184

not specifiedTotal: 81

SUCLG2-related disorderTotal: 7

Mitochondrial DNA depletion syndrome 9Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003848.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				25 clinvar	3 clinvar	28
missense			150 clinvar	5 clinvar	3 clinvar	158
nonsense			3 clinvar			3
start loss						0
frameshift			7 clinvar			7
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	162	30	6	198

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003848.4	RefSeq	NP_003839.2	11	MANE Select
ENST00000307227.10	Ensembl	ENSP00000307432.5	11	MANE Select
NM_001177599.2	RefSeq	NP_001171070.1	11	Standard
ENST00000460567.5	Ensembl	ENSP00000417260.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Citrate cycle (TCA cycle) - Homo sapiens (human)
Propanoate metabolism - Homo sapiens (human)
Valproic Acid Pathway, Pharmacodynamics
Pathway_PA165964473
Warburg Effect

Biological Process

tricarboxylic acid cycle
succinyl-CoA metabolic process
succinate metabolic process

Molecular Function

magnesium ion binding
succinate-CoA ligase (ADP-forming) activity
succinate-CoA ligase (GDP-forming) activity
protein binding
ATP binding

Cellular Component

mitochondrion
mitochondrial matrix
plasma membrane
succinate-CoA ligase complex (GDP-forming)

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000493112
Coding exons: 11
Length: 294155
Individuals with no LoFs: 124715
Homozygous LoFs: 1
Heterozygous LoFs: 78
Defined: 124794
p: 0.000317

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.488	244	223	1.09	0.0000114	2860
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00026	rare
Latino/Admixed American	0.00079	0.00078	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.00018	0.00017	rare
South Asian	0.00064	0.00059	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.498

Intolerance Scores

LoFtool: 0.900
RVIS EVS: 0.62
RVIS percentile EVS: 83.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.652

Gene Damage Prediction

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