SUCLG2

Chr 3

succinate-CoA ligase GDP-forming subunit beta

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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.50
Clinical SummarySUCLG2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.50LOEUF
pLI 0.000
Z-score -0.13
OE 1.03 (0.721.50)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.49Z-score
OE missense 1.09 (0.981.21)
244 obs / 223.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.03 (0.721.50)
00.351.4
Missense OE1.09 (0.981.21)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 20 / 19.4Missense obs/exp: 244 / 223.5Syn Z: 0.18
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SUCLG2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →