SUCLA2

Chr 13AR

succinate-CoA ligase ADP-forming subunit beta

Also known as: A-BETA, A-SCS, LINC00444, MTDPS5, SCS-betaA

The protein encodes the ATP-specific beta subunit of succinyl-CoA synthetase, which dimerizes with the alpha subunit to form an essential tricarboxylic acid cycle enzyme that hydrolyzes ATP to convert succinate to succinyl-CoA in the mitochondrial matrix. Biallelic mutations cause mitochondrial DNA depletion syndrome 5, an autosomal recessive encephalomyopathy that may present with or without methylmalonic aciduria. The pathogenic mechanism involves loss of function leading to impaired mitochondrial energy metabolism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.631 OMIM phenotype
Clinical SummarySUCLA2
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.63LOEUF
pLI 0.002
Z-score 2.97
OE 0.36 (0.220.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.02Z-score
OE missense 0.82 (0.730.92)
206 obs / 251.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.220.63)
00.351.4
Missense OE0.82 (0.730.92)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 9 / 25.1Missense obs/exp: 206 / 251.6Syn Z: 0.04
DN
0.6744th %ile
GOF
0.4875th %ile
LOF
0.3453th %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

SUCLA2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
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Top 3 full-text resultsSearch PubTator3 ↗