SUCLG2

Chr 3

succinate-CoA ligase GDP-forming subunit beta

Also known as: G-SCS, GBETA, GTPSCS

NCBI Gene: 8801 ENSG00000172340 UniProt: Q96I99 OMIM: 603922

The GTP-specific beta subunit of succinyl-CoA synthetase functions in the citric acid cycle, coupling the hydrolysis of succinyl-CoA to GTP synthesis and representing the only substrate-level phosphorylation step in the TCA cycle. Mutations cause mitochondrial DNA depletion syndrome, typically presenting in infancy with hypotonia, developmental delay, and progressive neurodegeneration, following autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants, suggesting that complete loss of protein function may be required for disease manifestation.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.50

Clinical Summary— SUCLG2

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

176 VUS of 268 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — SUCLG2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.50LOEUF

pLI 0.000

Z-score -0.13

OE 1.03 (0.72–1.50)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.49Z-score

OE missense 1.09 (0.98–1.21)

244 obs / 223.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.03 (0.72–1.50)

0≤0.351.4

Missense OE?1.09 (0.98–1.21)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 20 / 19.4Missense obs/exp: 244 / 223.5Syn Z: 0.18

This gene — mechanism propensity

0.6260th %ile

GOF

0.4973th %ile

LOF

0.4037th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

268 submitted variants in ClinVar

ClinVar

Classification Summary

VUS176

Likely Benign62

Benign21

Conflicting2

176

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	12	161	3	0	176
Likely Benign	0	3	29	30	62
Benign	1	6	11	3	21
Conflicting	—				2
Total	13	170	43	33	261

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap SUCLG2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →