SDHAF2
Succinate Dehydrogenase Complex Assembly Factor 2
Gene Information Card
| Symbol | SDHAF2 |
|---|---|
| Full Name | Succinate Dehydrogenase Complex Assembly Factor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q12.2 |
| NCBI Gene ID | 54949 ncbi.nlm.nih.gov/gene/54949 |
| Ensembl ID | ENSG00000167992 |
| UniProt ID | Q9NX18 |
| OMIM ID | 613019 |
| HGNC ID | 26034 |
| Aliases | SDH5, C11orf79, PGL2 |
Description
SDHAF2 (succinate dehydrogenase complex assembly factor 2) encodes a mitochondrial protein essential for the flavination of the SDHA subunit of succinate dehydrogenase (complex II). This assembly factor is required for the proper incorporation of the FAD cofactor into SDHA, enabling the enzyme's function in the tricarboxylic acid cycle and electron transport chain. Loss-of-function mutations in SDHAF2 are associated with hereditary paraganglioma-pheochromocytoma syndrome type 2 (PGL2).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Paraganglioma-Pheochromocytoma Syndrome (PGL2) | Loss-of-function mutations impair SDHA flavination, destabilizing complex II and leading to pseudohypoxic signaling via HIF1α stabilization | OMIM #613019; multiple families with germline SDHAF2 mutations |
| Paraganglioma | Same mechanism as PGL2; SDHAF2 mutations predispose to head and neck paragangliomas | ClinVar; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 8.2 | Medium |
| Skeletal Muscle | 7.5 | Medium |
| Liver | 5.1 | Low |
| Kidney | 4.8 | Low |
| Brain | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 6.3 | Embryonic kidney cells |
| HeLa | 5.7 | Cervical cancer cells |
| HepG2 | 4.9 | Hepatocellular carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.232G>A (p.Gly78Arg) | Missense | Rare (founder mutation in Dutch families) | Loss of function; disrupts SDHA interaction and FAD incorporation |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; prevents translation initiation |
| c.325C>T (p.Arg109*) | Nonsense | Rare | Loss of function; premature truncation |
Mutation functional classification
Loss of Function (LOF)
Most SDHAF2 mutations are loss-of-function, leading to impaired complex II assembly and pseudohypoxia.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not described; inheritance is autosomal dominant with incomplete penetrance due to haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
| • mitochondrial respiratory chain complex II assembly | • succinate dehydrogenase activity |
| • protein-containing complex binding | • mitochondrion |
| • FAD binding |
Pathways
• TCA cycle (KEGG: hsa00020)
• Oxidative phosphorylation (KEGG: hsa00190)
• Succinate dehydrogenase complex assembly
Protein Summary
SDHAF2 is a 166-amino acid mitochondrial matrix protein that acts as a specific assembly factor for succinate dehydrogenase (complex II). It binds to the SDHA subunit and facilitates the covalent attachment of the FAD cofactor, which is essential for enzymatic activity. Without SDHAF2, SDHA remains apoprotein and complex II is non-functional, leading to succinate accumulation and activation of hypoxia-inducible factors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SDHAF2 Knockout HEK293 Cell Line | EDJ-KQ16473 | Human | 54949 | Details Get a Quote |
| SDHAF2 Knockout A-549 Cell Line | EDJ-KQ48033 | Human | 54949 | Details Get a Quote |
| SDHAF2 Knockout HCT 116 Cell Line | EDJ-KQ48034 | Human | 54949 | Details Get a Quote |
| SDHAF2 Knockout HeLa Cell Line | EDJ-KQ48035 | Human | 54949 | Details Get a Quote |
