SDHD

Chr 11ARAD

succinate dehydrogenase complex subunit D

Also known as: CBT1, CII-4, CWS3, MC2DN3, PGL, PGL1, PPGL1, QPs3

NCBI Gene: 6392ENSG00000204370UniProt: O14521OMIM: 602690

This gene encodes a member of complex II of the respiratory chain, which is responsible for the oxidation of succinate. The encoded protein is one of two integral membrane proteins anchoring the complex to the matrix side of the mitochondrial inner membrane. Mutations in this gene are associated with the formation of tumors, including hereditary paraganglioma. Transmission of disease occurs almost exclusively through the paternal allele, suggesting that this locus may be maternally imprinted. There are pseudogenes for this gene on chromosomes 1, 2, 3, 7, and 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex II deficiency, nuclear type 3MIM #619167
AR
Paraganglioma and gastric stromal sarcomaMIM #606864
Pheochromocytoma/paraganglioma syndrome 1MIM #168000
AD

Clinical highlights

Gene-disease validity (ClinGen)
mitochondrial disease · ARLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total
Interpreting a novel variant
Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
84
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.73
LOEUF
Multiple*
Mechanism· G2P
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.73LOEUF
pLI 0.337
Z-score 2.09
OE 0.23 (0.09–0.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.17Z-score
OE missense 1.05 (0.89–1.25)
90 obs / 85.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.23 (0.09–0.73)
0≤0.351.4
Missense OE?1.05 (0.89–1.25)
0≤0.61.4
Synonymous OE?0.84
0≤1.21.6
LoF obs/exp: 2 / 8.6Missense obs/exp: 90 / 85.7Syn Z: 0.75

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SDHD · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients