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PEX19
peroxisomal biogenesis factor 19
PEX19 is located on the long (q) arm of chromosome 1, at band 1q23.2. Arm ratio per GRCh38 - banding schematic.
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Overview
PEX19 (peroxisomal biogenesis factor 19) is located on chromosome 1 and provides instructions for making a protein essential for building functional peroxisomes. These organelles are found in nearly all human cells and perform numerous metabolic tasks, including the breakdown of very-long-chain fatty acids and the synthesis of plasmalogens, which are specialised lipids required for nervous system development. The PEX19 protein acts as both a chaperone and an import receptor, recognising newly made peroxisomal membrane proteins in the cytoplasm and delivering them to the peroxisome surface. Without functional PEX19, cells cannot properly assemble peroxisomes, causing toxic metabolites to accumulate and essential biochemical pathways to fail. Inherited changes in PEX19 that severely impair protein function are associated with rare peroxisomal biogenesis disorders, which typically follow an autosomal recessive inheritance pattern.
What the gene does
The PEX19 protein functions as a cytosolic chaperone that binds to peroxisomal membrane proteins immediately after their synthesis. It recognises specific signal sequences within these proteins, preventing them from misfolding or aggregating before they reach the peroxisome. Once bound to its cargo, PEX19 transports the membrane protein to the peroxisome surface, where it interacts with another peroxisomal protein called PEX3. This interaction facilitates the insertion of the cargo protein into the peroxisome membrane. Beyond its role in protein import, PEX19 is also essential for the formation of new peroxisomes through a process called de novo biogenesis. During this process, PEX19 helps organise membrane proteins into pre-peroxisomal structures that mature into fully functional organelles. The protein's ability to maintain peroxisome number and integrity is particularly important during cell division, when peroxisomes must be distributed to daughter cells. Research suggests that PEX19 also participates in quality control mechanisms, ensuring that only properly folded membrane proteins are incorporated into peroxisomes.
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Chromosome location
PEX19 is located on the long arm of chromosome 1 at position 1q23.2. The gene spans a genomic region that includes six coding exons. This chromosomal location places PEX19 within a region containing several other genes involved in cellular metabolism and membrane trafficking. The gene is expressed in virtually all tissues, reflecting the universal requirement for peroxisomes in human cells.
Protein structure
The PEX19 protein comprises 299 amino acids and contains several functionally important regions. The N-terminal region from amino acids 1 to 63 is classified as disordered, lacking a fixed three-dimensional structure and potentially providing flexibility for protein-protein interactions. A region spanning amino acids 2 to 91 has been identified as necessary for PEX19 function in peroxisome biogenesis. Within this broader functional domain, a more specific segment from amino acids 2 to 56 mediates docking to the peroxisome membrane and binding to PEX3, the peroxisomal membrane anchor protein. The presence of intrinsically disordered regions may allow PEX19 to bind multiple different cargo proteins with varying structural features, enhancing its versatility as a chaperone.
Key variants
Pathogenic variants in PEX19 are rare but can have profound consequences for cellular function. Most disease-causing changes result in loss of protein function through mechanisms such as premature termination, frameshift alterations, or missense substitutions that disrupt critical protein-protein interactions. Because peroxisome assembly is essential for life, variants that completely abolish PEX19 function are typically associated with severe phenotypes manifesting in infancy. The spectrum of variants ranges from complete loss-of-function changes to hypomorphic alterations that retain some residual activity.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.161C>T | p.Ser54Leu | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 12A (Zellweger) |
c.577A>T | p.Lys193Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 12A (Zellweger) |
c.262del | p.Glu88fs | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 12A (Zellweger) |
c.294del | p.Glu98fs | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 12A (Zellweger) |
c.326C>G | p.Ser109Ter | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 12A (Zellweger) |
c.398dup | p.Ser134fs | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 12A (Zellweger) |
c.430C>T | p.Gln144Ter | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 12A (Zellweger) |
c.526C>T | p.Gln176Ter | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 12A (Zellweger) |
c.86del | p.Phe29fs | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 12A (Zellweger) |
c.9del | p.Ala4fs | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 12A (Zellweger) |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in PEX19 are linked to peroxisomal biogenesis disorders, a group of rare autosomal recessive conditions characterised by defective peroxisome assembly. These disorders present along a clinical spectrum, with the most severe forms causing developmental abnormalities, profound neurological impairment, liver dysfunction, and skeletal malformations that may be evident in early infancy. Milder presentations can include progressive neurological decline, vision impairment, and metabolic disturbances appearing later in childhood. The clinical variability often reflects the degree of residual PEX19 function, with some variants permitting partial peroxisome formation while others lead to near-complete peroxisome deficiency.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic PEX19 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
PEX19 is included on multiple NHS Genomic Medicine Service gene panels, reflecting its clinical relevance across several diagnostic pathways. The gene has green classification status on panels including Peroxisomal Disorders, Likely Inborn Error of Metabolism, Undiagnosed Metabolic Disorders, Intellectual Disability, Fetal Anomalies, Fetal Hydrops, Neonatal Cholestasis, Adult Onset Leukodystrophy, Arthrogryposis, Bilateral Congenital or Childhood Onset Cataracts, and Malformations of Cortical Development. Green status indicates strong evidence supporting the gene-disease relationship. This broad panel membership underscores the diverse clinical presentations that can arise from PEX19 dysfunction, ranging from prenatal manifestations to neurological and metabolic presentations across the lifespan. Testing through these NHS pathways is typically initiated when clinical features suggest a peroxisomal disorder.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
How is PEX19 inherited?
PEX19-related conditions follow an autosomal recessive inheritance pattern. This means an individual must inherit two altered copies of the gene, one from each parent, to develop the associated disorder. Carriers, who have one altered and one typical copy, generally do not show symptoms.
What happens when peroxisomes don't form properly?
When PEX19 variants prevent proper peroxisome assembly, cells cannot perform essential metabolic functions such as breaking down very-long-chain fatty acids or producing plasmalogens. This leads to toxic accumulation of certain substances and deficiency of others, affecting tissues with high metabolic demands such as the brain, liver, and eyes.
Can PEX19 variants be detected through carrier screening?
Yes, PEX19 is included in some carrier screening panels for autosomal recessive conditions. Carrier screening can identify individuals who carry one altered copy of the gene, which is particularly relevant for reproductive planning and understanding family risk, even though carriers themselves typically remain unaffected.