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SCP2
sterol carrier protein 2
SCP2 encodes sterol carrier protein 2, a protein critical for lipid transport and metabolism within cellular compartments called peroxisomes. The SCP2 gene provides instructions for making sterol carrier protein 2, which plays an essential role in transporting lipids and maintaining normal peroxisomal function.
SCP2 is located on the short (p) arm of chromosome 1, at band 1p32.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 1 in the library →Overview
The SCP2 gene, located on chromosome 1, encodes sterol carrier protein 2, a versatile protein involved in lipid transport and metabolism. This protein functions primarily within peroxisomes, small cellular compartments that break down fatty acids and process various lipids essential for normal cell function. Sterol carrier protein 2 facilitates the movement of cholesterol, fatty acids, and other lipid molecules between cellular membranes, supporting critical metabolic pathways.
When pathogenic variants disrupt SCP2 function, the resulting impairment in lipid processing can affect multiple organ systems, particularly the nervous system. The gene follows an autosomal recessive inheritance pattern, meaning affected individuals typically inherit altered copies from both parents. Clinical recognition of SCP2-related disorders has grown as genetic testing has become more widely available for metabolic and neurological conditions.
What the gene does
Sterol carrier protein 2 performs several interconnected roles in cellular lipid metabolism. The protein binds and transports lipid molecules, including cholesterol, fatty acids, and phospholipids, facilitating their movement between different cellular compartments. This transport function proves particularly important in peroxisomes, where the protein supports the breakdown of very long chain fatty acids and the synthesis of certain lipid molecules.
Beyond simple transport, the protein participates in regulating lipid homeostasis by influencing how cells process and distribute different types of fats. Research suggests that sterol carrier protein 2 may also contribute to cellular signalling pathways related to lipid sensing and metabolic regulation. The protein's activity helps maintain the proper balance of lipids in cell membranes and ensures that peroxisomes can effectively carry out their metabolic functions, which are essential for normal brain development and myelin maintenance in the nervous system.
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Chromosome location
SCP2 resides on the short arm of chromosome 1 at position 1p32.3. This chromosomal region contains multiple genes involved in metabolic processes. The gene's location in the genome does not appear to place it in a region particularly prone to large deletions or duplications, though point mutations and small insertions or deletions can occur throughout the coding sequence.
Protein structure
The canonical form of sterol carrier protein 2 spans 547 amino acids and contains distinct functional regions. The SCP2 domain, extending from amino acids 433 to 543, represents the core functional unit responsible for lipid binding and transport activities. This domain adopts a characteristic fold that creates a hydrophobic pocket capable of accommodating various lipid molecules. At the protein's C-terminus, a microbody targeting signal comprising the final three amino acids (positions 545 to 547) directs the protein to peroxisomes, ensuring proper subcellular localisation essential for its metabolic functions. A short linker region between the SCP2 domain and the targeting signal allows proper positioning of both functional elements.
Key variants
Pathogenic variants in SCP2 can disrupt the protein's ability to bind lipids, impair its transport function, or prevent proper targeting to peroxisomes. Loss-of-function variants typically result from missense changes that alter functionally critical amino acids within the SCP2 domain or from nonsense and frameshift variants that truncate the protein. The autosomal recessive inheritance pattern means that individuals with one pathogenic variant typically remain unaffected, whilst those inheriting variants from both parents may develop metabolic or neurological symptoms.
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.1111C>T | p.Gln371Ter | Pathogenic | ★★☆☆ | Sterol carrier protein 2 deficiency |
c.588dup | - | Pathogenic/Likely pathogenic | ★★☆☆ | Sterol carrier protein 2 deficiency |
c.825+1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | SCP2-related disorder |
g.(?_53407448)_(53446235_?)del | - | Pathogenic | ★☆☆☆ | not provided |
g.(?_53420392)_(53420496_?)del | - | Pathogenic | ★☆☆☆ | not provided |
c.103_125dup | p.Gly43fs | Pathogenic | ★☆☆☆ | not provided |
c.1135_1136dup | p.Gln380fs | Pathogenic | ★☆☆☆ | not provided |
c.1170dup | p.Asn391Ter | Pathogenic | ★☆☆☆ | not provided |
c.151C>T | p.Gln51Ter | Pathogenic | ★☆☆☆ | not provided |
c.229_232del | p.Tyr77fs | Pathogenic | ★☆☆☆ | not provided |
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
Disruption of SCP2 function has been associated with peroxisomal disorders that primarily affect the nervous system and metabolism. Individuals with biallelic pathogenic variants may present with white matter abnormalities visible on brain imaging, developmental delays, and features consistent with inherited metabolic disease. The severity and specific manifestations can vary depending on how severely the variants impair protein function. Some affected individuals show predominantly neurological features, whilst others may have broader metabolic disturbances reflecting the protein's role in multiple lipid-processing pathways.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic SCP2 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
Within the NHS Genomic Medicine Service, SCP2 appears on several green-rated gene panels, reflecting its established clinical validity for specific diagnostic contexts. The gene is included in the Inherited white matter disorders panel, the Peroxisomal disorders panel, and the White matter disorders and cerebral calcification narrow panel, indicating its recognised role in conditions affecting brain white matter. It also features on the Likely inborn error of metabolism panel and the Undiagnosed metabolic disorders panel, supporting its use in the investigation of unexplained metabolic presentations. Green ratings confirm the gene's clinical validity in these diagnostic contexts.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does sterol carrier protein 2 do in the body?
Sterol carrier protein 2 transports lipids such as cholesterol and fatty acids within cells, particularly in peroxisomes. This transport activity supports essential metabolic processes including the breakdown of very long chain fatty acids and maintenance of lipid balance in cell membranes.
How are SCP2 variants inherited?
SCP2 follows an autosomal recessive inheritance pattern. This means an individual must inherit a pathogenic variant from both parents to develop related conditions. Carriers with one variant copy typically show no symptoms.
Why is SCP2 included on NHS gene panels for white matter disorders?
SCP2 dysfunction can disrupt lipid metabolism essential for maintaining myelin and white matter in the brain. Pathogenic variants may cause white matter abnormalities detectable on brain imaging, making the gene clinically relevant for investigating inherited white matter disorders.