PEX6

Chr 6ARAD

peroxisomal biogenesis factor 6

Also known as: HMLR2, PAF-2, PAF2, PBD4A, PDB4B, PXAAA1

This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) family of ATPases. This member is a predominantly cytoplasmic protein, which plays a direct role in peroxisomal protein import and is required for PTS1 (peroxisomal targeting signal 1, a C-terminal tripeptide of the sequence ser-lys-leu) receptor activity. Mutations in this gene cause peroxisome biogenesis disorders of complementation group 4 and complementation group 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

OMIMResearchGenerating clinical summary…
LOFmechanismAR/ADLOEUF 0.653 OMIM phenotypes
Clinical SummaryPEX6
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Gene-Disease Validity (ClinGen)
peroxisome biogenesis disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.65LOEUF
pLI 0.000
Z-score 3.21
OE 0.42 (0.280.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.44Z-score
OE missense 0.82 (0.760.89)
436 obs / 529.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.42 (0.280.65)
00.351.4
Missense OE?0.82 (0.760.89)
00.61.4
Synonymous OE?0.97
01.21.6
LoF obs/exp: 15 / 35.7Missense obs/exp: 436 / 529.4Syn Z: 0.36
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderatePEX6-related Heimler syndrome 2OTHERAR
definitivePEX6-related peroxisome biogenesis disorder 4BLOFAR
definitivePEX6-related peroxisome biogenesis disorder 4A (Zellweger)LOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6839th %ile
GOF
0.5661th %ile
LOF
0.3260th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNWe showed that the PEX6 p.Arg860Trp change has a dominant-negative effect on the function of the PEX1-PEX6 complex in peroxisomal matrix protein import.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

  1. 1.PMID 29220678

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PEX6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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