SDHA

Chr 5ARAD

succinate dehydrogenase complex flavoprotein subunit A

The protein functions as the major catalytic subunit of succinate-ubiquinone oxidoreductase (mitochondrial complex II) in the inner mitochondrial membrane, catalyzing electron transfer in the respiratory chain. Mutations cause mitochondrial complex II deficiency leading to Leigh syndrome, neurodegeneration with ataxia and late-onset optic atrophy, dilated cardiomyopathy, and pheochromocytoma/paraganglioma syndrome through loss of function. Inheritance can be either autosomal recessive or autosomal dominant depending on the specific mutation and associated phenotype.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAR/ADLOEUF 0.864 OMIM phenotypes
Clinical SummarySDHA
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Gene-Disease Validity (ClinGen)
hereditary pheochromocytoma-paraganglioma · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

4 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.22
OE 0.60 (0.420.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.74Z-score
OE missense 0.89 (0.820.98)
346 obs / 387.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.420.86)
00.351.4
Missense OE0.89 (0.820.98)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 21 / 35.2Missense obs/exp: 346 / 387.3Syn Z: -1.41
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSDHA-related paragangliomasLOFAD
definitiveSDHA-related Leigh syndromeOTHERAR
DN
0.7229th %ile
GOF
0.5661th %ile
LOF
0.3551th %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

SDHA · 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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