Fumarase deficiency: genes and variants
Fumarase deficiency is linked to 1 analyzed protein (FH). 11 DNA variants are known to cause it; 111 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Fumarase deficiency
FH: Fumarate hydratase, mitochondrial
It converts fumarate to malate in the mitochondrial TCA cycle. Biallelic loss causes fumarase deficiency, while heterozygous loss-of-function variants cause hereditary leiomyomatosis and renal cell cancer syndrome through fumarate accumulation and tumor-suppressor loss.
11 disease-causing and 111 uncertain variants in FH are linked to Fumarase deficiency.
Known disease-causing variants in Fumarase deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| FH K230R | 230 | Disease-causing (★★) | |
| FH H318L | 318 | Disease-causing (★★) | |
| FH T234A | 234 | Disease-causing (★★) | |
| FH G397R | 397 | Disease-causing (★★) | |
| FH T72P | 72 | Disease-causing (★★) | |
| FH N188I | 188 | Disease-causing (★★) | |
| FH M195V | 195 | Disease-causing (★★) | |
| FH L218P | 218 | Disease-causing (★★) | |
| FH G346D | 346 | Disease-causing (★★) | |
| FH L453P | 453 | Disease-causing (★★) | |
| FH S222P | 222 | Disease-causing (★) |
Same protein, different disease
- Hereditary leiomyomatosis and renal cell cancer is also caused by FH variants; they fall mostly in different places as the Fumarase deficiency variants (34 disease-causing).
Diseases related to Fumarase deficiency
- Ovarian cancer, also linked to FH
- Hereditary leiomyomatosis and renal cell cancer, also linked to FH
- Inherited phaeochromocytoma and paraganglioma excluding NF1, also linked to FH
Frequently asked questions
Which genes are linked to Fumarase deficiency?
In CATVariant, Fumarase deficiency is linked to 1 analyzed protein: FH (Fumarate hydratase, mitochondrial).
How many genetic variants are linked to Fumarase deficiency?
124 variants: 11 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 111 are of uncertain significance or have conflicting reports.
Which uncertain variants in Fumarase deficiency look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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