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SNX10
sorting nexin 10
SNX10 is located on the short (p) arm of chromosome 7, at band 7p15.2. Arm ratio per GRCh38 - banding schematic.
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Overview
SNX10 is located on chromosome 7 and encodes sorting nexin 10, a member of the sorting nexin protein family involved in intracellular membrane trafficking. The encoded protein performs a specialised role in bone-resorbing cells by directing the vacuolar-type H+-ATPase complex to the ruffled border membrane where osteoclasts interface with bone. This targeting step is essential for breaking down mineralised bone matrix, a process that enables skeletal remodelling throughout life.
Pathogenic variants in SNX10 follow an autosomal recessive inheritance pattern, meaning affected individuals carry alterations in both gene copies. When SNX10 function becomes lost, osteoclasts cannot effectively resorb bone, leading to abnormally dense skeletal tissue and associated clinical features. The gene is included in UK NHS genomic testing panels for skeletal disorders.
What the gene does
Sorting nexin 10 directs membrane protein transport within osteoclasts, with particular importance for positioning the V-ATPase proton pump at specific cellular locations. By pumping protons into the sealed compartment between osteoclasts and underlying bone, the V-ATPase creates an acidic microenvironment that dissolves mineral crystals and permits enzymatic breakdown of the organic bone scaffold. When SNX10 cannot perform its trafficking role, V-ATPase fails to reach the ruffled border membrane in adequate amounts, undermining the acidification process that bone resorption requires.
This regulatory function depends on the protein's phosphatidylinositol-binding PX domain, which recognises specific lipid signals decorating membrane surfaces and guides cargo proteins toward their proper intracellular destinations. SNX10 also binds directly to the ATP6V1D subunit of the V-ATPase apparatus through a distinct molecular interface, creating a physical link between transport machinery and its payload. Whilst other sorting nexins participate broadly in endosomal sorting and receptor recycling, SNX10 appears particularly crucial within the osteoclast lineage.
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Chromosome location
SNX10 is positioned at chromosomal band 7p15.2 on the short arm of chromosome 7. The gene spans a relatively compact genomic region and produces a transcript encoding a 201-amino-acid protein. This chromosomal location has been confirmed through physical mapping studies and genomic sequence assembly.
Protein structure
The sorting nexin 10 protein comprises 201 amino acids organised into distinct functional regions. The PX domain spans amino acids 10 to 127 and mediates recognition of phosphatidylinositol phospholipids on intracellular membranes, enabling the protein to localise to specific membrane compartments. Overlapping with the PX domain, a region required for interaction with ATP6V1D extends from amino acids 8 to 125, providing the molecular interface for binding the V-ATPase complex. The C-terminal portion of the protein contains a disordered region from amino acids 156 to 201, which may provide flexibility for protein-protein interactions or regulatory modifications.
Key variants
Pathogenic variants in SNX10 are associated with autosomal recessive skeletal disorders characterised by impaired osteoclast function. Disease-causing changes include nonsense variants that introduce premature stop codons, frameshift variants resulting from small insertions or deletions, and missense variants affecting critical residues within the PX domain or V-ATPase interaction region. The distribution of pathogenic variants reflects the functional importance of these domains for protein activity.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Biallelic pathogenic variants in SNX10 cause autosomal recessive osteopetrosis, a rare skeletal disorder marked by abnormally dense bones due to defective osteoclast-mediated bone resorption. Affected individuals may present with fractures despite increased bone density, progressive cranial nerve compression due to narrowed foramina, and potential haematopoietic complications when marrow spaces become restricted. The severity and age of onset can vary depending on the specific variants present. Additional skeletal features may include hydrocephalus secondary to skull base abnormalities and other bone malformations detectable during foetal development.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic SNX10 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
SNX10 is included on multiple UK NHS Genomic Medicine Service testing panels reflecting its role in skeletal development and bone homeostasis. The gene holds green classification status on the Osteopetrosis panel (R104.4), Skeletal dysplasia panel (R104), Hydrocephalus panel (R86), and Fetal anomalies panel (R21), indicating sufficient evidence for clinical diagnostic use in these contexts. It also appears on the COVID-19 research panel, reflecting investigations into genetic factors potentially influencing disease outcomes. These panel memberships guide when SNX10 sequencing may be appropriate during clinical genomic investigations in the NHS.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What inheritance pattern does SNX10 follow?
SNX10-related conditions follow an autosomal recessive inheritance pattern. This means an individual must inherit pathogenic variants in both copies of the gene (one from each parent) to be affected. Carriers with one pathogenic variant typically do not show symptoms.
How does SNX10 relate to bone density?
SNX10 enables osteoclasts to break down bone tissue normally by ensuring proper delivery of acid-producing machinery to the cell-bone interface. Loss of SNX10 function prevents efficient bone resorption, causing bones to become excessively dense but paradoxically more prone to fracture due to abnormal structure.
Is SNX10 testing available through the NHS?
Yes, SNX10 is included on several NHS Genomic Medicine Service panels, including those for osteopetrosis, skeletal dysplasia, and hydrocephalus. Testing may be arranged through clinical genetics services when a patient's features suggest one of these conditions.