PEX6

Chr 6ARAD

peroxisomal biogenesis factor 6

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
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.
📖
GeneReview available — PEX6
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

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 OE0.42 (0.280.65)
00.351.4
Missense OE0.82 (0.760.89)
00.61.4
Synonymous OE0.97
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

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.PMID:29220678

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

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗