Mitochondrial trifunctional protein deficiency: genes and variants
Mitochondrial trifunctional protein deficiency is linked to 1 analyzed protein (HADHB). 22 DNA variants are known to cause it; 113 more are uncertain, and 4 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: mitochondrial trifunctional protein deficiency 1; mitochondrial trifunctional protein deficiency 2
Genes linked to Mitochondrial trifunctional protein deficiency
HADHB: Trifunctional enzyme subunit beta, mitochondrial
It provides two enzymatic activities of the mitochondrial trifunctional complex required for long-chain fatty-acid beta-oxidation. Biallelic pathogenic variants can cause mitochondrial trifunctional-protein deficiency or long-chain 3-hydroxyacyl-CoA dehydrogenase-related disease, with cardiomyopathy, hypoglycemia, neuropathy, or rhabdomyolysis.
22 disease-causing and 113 uncertain variants in HADHB are linked to Mitochondrial trifunctional protein deficiency.
Known disease-causing variants in Mitochondrial trifunctional protein deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| HADHB R61H | 61 | Disease-causing (★★) | |
| HADHB R247H | 247 | Disease-causing (★★) | |
| HADHB R247C | 247 | Disease-causing (★★) | |
| HADHB N114D | 114 | Disease-causing (★★) | |
| HADHB P294R | 294 | Disease-causing (★★) | |
| HADHB N389D | 389 | Disease-causing (★★) | |
| HADHB A392V | 392 | Disease-causing (★★) | |
| HADHB F430S | 430 | Disease-causing (★★) | |
| HADHB G434V | 434 | Disease-causing (★★) | |
| HADHB V455G | 455 | Disease-causing (★★) | |
| HADHB M1V | 1 | Disease-causing (★★) | |
| HADHB P130L | 130 | Disease-causing (★) | |
| HADHB M136T | 136 | Disease-causing (★) | |
| HADHB P355T | 355 | Disease-causing (★) | |
| HADHB Q143E | 143 | Disease-causing (★) | |
| HADHB A131V | 131 | Disease-causing (★) | |
| HADHB G301R | 301 | Disease-causing (★) | |
| HADHB S383L | 383 | Disease-causing (★) | |
| HADHB A459T | 459 | Disease-causing (★) | |
| HADHB R61C | 61 | Disease-causing | |
| HADHB D263G | 263 | Disease-causing | |
| HADHB R444K | 444 | Disease-causing |
Uncertain variants in Mitochondrial trifunctional protein deficiency that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| HADHB G301S | 301 | Conflicting reports (★) | +6: G301R at the same position is pathogenic; REVEL 0.980 | |
| HADHB N114S | 114 | Conflicting reports (★) | +6: in a 3D region that tolerates change poorly (1R); N114D at the same position is pathogenic; REVEL 0.807 | |
| HADHB P355L | 355 | Uncertain (★★) | +6: in a 3D region that tolerates change poorly (1R); P355T at the same position is pathogenic; REVEL 0.959 | |
| HADHB P130S | 130 | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; P130L at the same position is pathogenic; REVEL 0.940 |
Frequently asked questions
Which genes are linked to Mitochondrial trifunctional protein deficiency?
In CATVariant, Mitochondrial trifunctional protein deficiency is linked to 1 analyzed protein: HADHB (Trifunctional enzyme subunit beta, mitochondrial).
How many genetic variants are linked to Mitochondrial trifunctional protein deficiency?
154 variants: 22 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 113 are of uncertain significance or have conflicting reports.
Which uncertain variants in Mitochondrial trifunctional protein deficiency look disease-causing?
4 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example HADHB G301S, HADHB N114S, HADHB P355L and HADHB P130S. These are leads for expert review, not diagnoses.
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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