Bifunctional peroxisomal enzyme deficiency: genes and variants

Genes linked to Bifunctional peroxisomal enzyme deficiency

• HSD17B4: Peroxisomal multifunctional enzyme type 2

  A peroxisomal multifunctional enzyme that carries out two steps in fatty-acid beta-oxidation. It processes straight-chain and branched fatty acids as well as bile-acid intermediates, and loss of the protein causes D-bifunctional protein deficiency.

  33 disease-causing and 212 uncertain variants in HSD17B4 are linked to Bifunctional peroxisomal enzyme deficiency.

Where Bifunctional peroxisomal enzyme deficiency variants cluster

• HSD17B4 (3R)-hydroxyacyl-CoA dehydrogenase (positions 1–305): 21 of 33 disease-causing changes, 1.5× more than its size predicts.

Known disease-causing variants in Bifunctional peroxisomal enzyme deficiency

Uncertain variants in Bifunctional peroxisomal enzyme deficiency that look disease-causing

Which prediction tools work for Bifunctional peroxisomal enzyme deficiency

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• REVEL: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 99 out of 100
• PolyPhen-2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 96 out of 100
• ESM1b (LLR): 96 out of 100
• CADD: 87 out of 100
• phyloP: 86 out of 100

Diseases related to Bifunctional peroxisomal enzyme deficiency

• Perrault syndrome, also linked to HSD17B4

Frequently asked questions

Which genes are linked to Bifunctional peroxisomal enzyme deficiency?

In CATVariant, Bifunctional peroxisomal enzyme deficiency is linked to 1 analyzed protein: HSD17B4 (Peroxisomal multifunctional enzyme type 2).

How many genetic variants are linked to Bifunctional peroxisomal enzyme deficiency?

255 variants: 33 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 212 are of uncertain significance or have conflicting reports.

Which uncertain variants in Bifunctional peroxisomal enzyme deficiency look disease-causing?

3 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example HSD17B4 A196V, HSD17B4 N98S and HSD17B4 L405F. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Bifunctional peroxisomal enzyme deficiency?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.99, based on 33 disease-causing and 15 harmless variants).

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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