PEX6

Chr 6

peroxisomal biogenesis factor 6

NCBI Gene: 5190 ENSG00000124587 UniProt: Q13608

The protein is a cytoplasmic AAA family ATPase that directly imports proteins into peroxisomes and is required for PTS1 receptor activity. Mutations cause autosomal recessive peroxisome biogenesis disorders including Zellweger syndrome (PBD4A), milder PBD4B, and Heimler syndrome 2, as well as autosomal dominant disease. The pathogenic mechanism involves dominant-negative effects disrupting peroxisomal protein import.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling (PubMed:16314507, PubMed:16854980, PubMed:21362118, PubMed:29884772). Specifically recognizes PEX5 monoubiquitinated at 'Cys-11', and pulls it out of the peroxisome lumen through the PEX2-PEX10-PEX12 retrotranslocation channel (PubMed:29884772). Extraction by the PEX1-PEX6 AAA ATPase complex is accompanied by unfolding of the TPR repeats and release of bound cargo from PEX5 (PubMed:29884772)

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPeroxisome biogenesis disorder complementation group 4

UniProtPeroxisome biogenesis disorder 4A

UniProtPeroxisome biogenesis disorder 4B

UniProtHeimler syndrome 2

Clinical highlights

Gene-disease validity (ClinGen)

peroxisome biogenesis disorder · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.65

LOEUF

LOF

Mechanism· G2P

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