SDHB

Chr 1

succinate dehydrogenase complex iron sulfur subunit B

Also known as: CWS2, IP, MC2DN4, PGL4, PPGL4, SDH, SDH1, SDH2

NCBI Gene: 6390ENSG00000117118UniProt: P21912

This tumor suppressor gene encodes the iron-sulfur protein subunit of the succinate dehydrogenase (SDH) enzyme complex which plays a critical role in mitochondria. The SDH enzyme complex is composed of four nuclear-encoded subunits. This enzyme complex converts succinate to fumarate which releases electrons as part of the citric acid cycle, and the enzyme complex additionally provides an attachment site for released electrons to be transferred to the oxidative phosphorylation pathway. The SDH enzyme complex plays a role in oxygen-related gene regulation through its conversion of succinate, which is an oxygen sensor that stabilizes the hypoxia-inducible factor 1 (HIF1) transcription factor. Sporadic and familial mutations in this gene result in paragangliomas, pheochromocytoma, and gastrointestinal stromal tumors, supporting a link between mitochondrial dysfunction and tumorigenesis. Mutations in this gene are also implicated in nuclear type 4 mitochondrial complex II deficiency. [provided by RefSeq, Jun 2022]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPheochromocytoma/paraganglioma syndrome 4
UniProtParaganglioma and gastric stromal sarcoma
UniProtMitochondrial complex II deficiency, nuclear type 4

Clinical highlights

Gene-disease validity (ClinGen)
mitochondrial disease · ARDefinitivesufficient evidence for diagnostic panels2 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.
1
Active trials
261
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.82
LOEUF
Multiple*
Mechanism· G2P
📖
GeneReview available — SDHB
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.82LOEUF
pLI 0.000
Z-score 2.13
OE 0.47 (0.28–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.10Z-score
OE missense 1.02 (0.90–1.17)
158 obs / 154.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.47 (0.28–0.82)
0≤0.351.4
Missense OE?1.02 (0.90–1.17)
0≤0.61.4
Synonymous OE?1.00
0≤1.21.6
LoF obs/exp: 9 / 19.0Missense obs/exp: 158 / 154.4Syn Z: 0.02

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SDHB · protein map & ClinVar variants

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

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