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SLC25A24
solute carrier family 25 member 24
The SLC25A24 gene provides instructions for a protein crucial in mitochondrial function, particularly for transporting molecules vital for energy production within cells. SLC25A24 encodes a mitochondrial carrier protein belonging to the solute carrier family.
SLC25A24 is located on the short (p) arm of chromosome 1, at band 1p13.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The SLC25A24 gene, also known as solute carrier family 25 member 24, is involved in producing a protein that plays a key role in mitochondrial processes. Mitochondria are the primary sites of cellular energy production, generating most of the cell's adenosine triphosphate (ATP) supply, which serves as a chemical energy source.
The protein encoded by SLC25A24 is a member of the solute carrier (SLC) family of proteins, a large group recognised for moving various substances across cellular membranes. Specifically, the SLC25A24 protein mediates the transport of particular molecules across the inner membrane of the mitochondria. This transport is essential for maintaining efficient cellular energy production and metabolic pathways.
What the gene does
The SLC25A24 gene product functions as a mitochondrial ATP-Mg/Pi carrier. This means it is responsible for transporting ATP molecules, which are bound to magnesium (Mg), across the inner mitochondrial membrane. This transport happens in exchange for phosphate (Pi) atoms. This exchange mechanism is vital for several fundamental cellular processes [PMID:33675013].
Efficient energy generation within cells depends critically on the proper functioning of this carrier protein. Beyond energy production, the SLC25A24 protein also contributes to the synthesis and breakdown of various molecules, a process known as metabolism, and is involved in protein production within cells. Precise regulation of these transport activities helps ensure an optimal mitochondrial environment for these essential biological functions [PMID:24077649].
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Chromosome location
The SLC25A24 gene is located on chromosome 1, specifically at position 1p13.3. Chromosomes are organised structures of DNA and proteins found within the nucleus of human cells; each chromosome has a distinct short arm ('p') and long arm ('q'). The '1p13.3' designation refers to band 13.3 on the short arm of chromosome 1. This specific genomic address helps in mapping the gene's position and understanding its genetic context within the human genome.
Protein structure
The SLC25A24 protein is 477 amino acids long and has a complex domain architecture suitable for its role as a mitochondrial carrier [PMID:24077649]. It features a regulatory N-terminal domain spanning amino acids 1-173, which contains several crucial calcium-binding motifs. Within this regulatory region are four distinct EF-hand domains: EF-hand 1 (amino acids 19-54), EF-hand 2 (amino acids 55-88), EF-hand 3 (amino acids 86-121), and EF-hand 4 (amino acids 122-157). These EF-hand motifs are characteristic calcium-binding structures.
A Linker region (amino acids 159-168) connects the regulatory N-terminal part to the C-terminal transmembrane transporter domain (amino acids 174-477). The C-terminal domain is responsible for the transport function and contains three conserved Solcar repeats: Solcar 1 (amino acids 192-278), Solcar 2 (amino acids 286-371), and Solcar 3 (amino acids 383-471). These repeats are characteristic features of mitochondrial carrier proteins.
Key variants
Genetic variants in the SLC25A24 gene can alter the protein's structure or function, potentially impacting its ability to transport molecules across the mitochondrial membrane efficiently. These genetic changes can range from small alterations in the DNA sequence to larger structural rearrangements. The inheritance pattern for conditions associated with SLC25A24 variants can vary, indicating different ways these genetic changes are passed down through families. The specific impact of a variant often depends on its location within the gene and how it affects the critical functional domains of the SLC25A24 protein.
Sample of pathogenic variants
3 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.649C>T | p.Arg217Cys | Pathogenic | ★★☆☆ | Fontaine progeroid syndrome |
c.650G>A | p.Arg217His | Pathogenic/Likely pathogenic | ★★☆☆ | Fontaine progeroid syndrome |
c.758G>C | p.Gly253Ala | Likely pathogenic | ★☆☆☆ | Dementia |
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
Variants within the SLC25A24 gene have been associated with specific inherited conditions. Two notable conditions linked to SLC25A24 mutations are Gorlin-Chaudhry-Moss syndrome and Fontaine syndrome (also known as Petty-type congenital progeroid syndrome). These conditions share some clinical features.
Gorlin-Chaudhry-Moss syndrome has been observed exclusively in females and is characterised by skull abnormalities affecting the head and face, a lack of fatty tissue under the skin (lipodystrophy), and excessive hair growth (hypertrichosis) on the face and body. Fontaine syndrome presents with many similar characteristics, including skull abnormalities and lipodystrophy.
No disease links recorded for this gene in our reference set.
UK clinical status
The SLC25A24 gene is currently included in several genetic testing panels within the NHS Genomic Medicine Service, reflecting its recognised clinical significance in the UK. It is part of the DDG2P panel, indicating its association with developmental disorders. Additionally, it is listed on panels for Foetal anomalies (R21), Likely inborn error of metabolism (R98), Mitochondrial disorders, Rare syndromic craniosynostosis or isolated multisuture synostosis (R100), and Structural eye disease (R36). This inclusion means that variants in SLC25A24 may be analysed in patients presenting with symptoms related to these clinical areas.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
Currently, there is no conclusive research to suggest specific lifestyle modifications, such as dietary changes or exercise regimens, can prevent conditions associated with variants in the SLC25A24 gene. However, maintaining a generally healthy lifestyle is beneficial for overall well-being. This typically includes a balanced diet rich in essential nutrients, regular physical activity, and adequate sleep. General population health advice promotes these habits for supporting cellular health and metabolic function.
Supplement considerations
There is no scientific evidence to support the claim that any specific dietary supplements can prevent, treat, or improve outcomes for conditions associated with SLC25A24 gene variants. Individuals considering any supplements should consult a healthcare professional. A healthcare provider can offer personalised advice, assess potential risks, and ensure that any supplement use does not interfere with existing medical treatments or conditions.
Frequently asked questions
What is the primary function of the SLC25A24 gene?
The SLC25A24 gene provides instructions for a mitochondrial carrier protein. This protein transports ATP bound to magnesium (ATP-Mg) and exchanges it for phosphate across the inner mitochondrial membrane, which is critical for cellular energy production.
What conditions are associated with variants in the SLC25A24 gene?
Variants in the SLC25A24 gene are associated with Gorlin-Chaudhry-Moss syndrome and Fontaine syndrome (also known as Petty-type congenital progeroid syndrome). These conditions share features affecting skull development and fat distribution.
Is Gorlin-Chaudhry-Moss syndrome only found in females?
According to available information, Gorlin-Chaudhry-Moss syndrome, associated with SLC25A24 variants, has been described exclusively in females.
What is the difference between Gorlin-Chaudhry-Moss syndrome and Fontaine syndrome?
Both conditions share features such as skull abnormalities and lipodystrophy. However, Gorlin-Chaudhry-Moss syndrome has only been reported in females and includes hypertrichosis.
Where is the SLC25A24 gene located?
The SLC25A24 gene is located on the short arm of chromosome 1, at position 1p13.3.
References
- Ehmke N, Graul-Neumann L, Smorag L. De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction. American journal of human genetics. 2017. PMID: 29100093
- Writzl K, Maver A, Kovačič L. De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise. American journal of human genetics. 2017. PMID: 29100094
- Run C, Yang Q, Liu Z. Molecular Basis of MgATP Selectivity of the Mitochondrial SCaMC Carrier. Structure (London, England : 1993). 2015. PMID: 26165595