On this page
SLC35A2
solute carrier family 35 member A2
SLC35A2 is located on the short (p) arm of chromosome X, at band Xp11.23. Arm ratio per GRCh38 - banding schematic.
Explore chromosome X in the library →Available at Jeen Health
Clinical tests that include this
Overview
SLC35A2 is located on the X chromosome and encodes UDP-galactose translocator (UGT), a membrane-spanning enzyme that facilitates glycosylation. Glycosylation involves attaching complex sugar chains to proteins and lipids, enabling them to perform their cellular roles correctly. The gene produces two slightly different enzyme versions, UGT1 and UGT2, which differ by only a few amino acids but can operate independently or together in various cellular locations.
Pathogenic changes in SLC35A2 result in congenital disorders of glycosylation, a group of inherited conditions characterised by impaired sugar-chain assembly. These disorders typically manifest with neurological features including epilepsy, intellectual disability, and developmental delay, alongside abnormalities affecting multiple organ systems. Because SLC35A2 is X-linked, the inheritance pattern and clinical presentation differ between males and females.
What the gene does
The UDP-galactose translocator protein functions as a membrane transporter within the endoplasmic reticulum and Golgi apparatus, moving UDP-galactose from the cytoplasm into these compartments where glycosylation occurs. This transport step is essential because galactose must be delivered to the correct cellular location before it can be incorporated into growing oligosaccharide chains attached to proteins and lipids.
During glycosylation, the enzyme facilitates the addition of galactose at specific positions within the sugar chain structure. The process follows a precise sequence: simple sugars are linked together in the correct order, and once the oligosaccharide chain reaches its proper configuration, it is attached to target proteins or lipids. This modification alters the three-dimensional structure and function of these molecules, affecting processes ranging from cell signalling to structural stability.
The two isoforms produced from SLC35A2, UGT1 and UGT2, exhibit functional versatility by operating in different cellular compartments. This flexibility allows cells to maintain glycosylation capacity across various organelles, ensuring that proteins and lipids receive appropriate sugar modifications regardless of where they are processed within the cell.
Video: Genetics 101
Chromosome location
SLC35A2 is located on the short arm of the X chromosome at position Xp11.23. This chromosomal location places the gene within a region containing numerous genes involved in neurological development and metabolic processes. The X-linked position means that males, possessing only one X chromosome, are typically more severely affected by pathogenic variants than females, who may have a second functional copy on their other X chromosome providing partial compensation.
Protein structure
The SLC35A2 protein comprises 396 amino acids organised into a structure typical of solute carrier family transporters. The protein contains a disordered region spanning amino acids 358 to 379, which likely provides flexibility for conformational changes during substrate transport. At the C-terminus, an ER retention motif occupies amino acids 392 to 396, ensuring the protein remains localised to the endoplasmic reticulum and Golgi apparatus where glycosylation takes place. These structural features enable the transporter to maintain its position within the appropriate cellular membranes whilst facilitating the movement of UDP-galactose across them.
Key variants
At least nine pathogenic variants in SLC35A2 have been identified that cause congenital disorders of glycosylation. These variants typically result in single amino acid substitutions that impair the transporter's ability to move UDP-galactose effectively, or they may disrupt protein stability and cellular localisation. The severity of clinical manifestations generally correlates with how significantly a variant reduces transporter function, though X-inactivation patterns in females can influence the clinical picture substantially.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Pathogenic variants in SLC35A2 cause SLC35A2-congenital disorder of glycosylation (SLC35A2-CDG), an inherited condition characterised primarily by neurological abnormalities. Affected individuals typically present with epilepsy that may begin in infancy, developmental delay of varying severity, and intellectual disability. Additional features can include malformations of cortical development, affecting the outer layer of the brain, and abnormalities in other organ systems reflecting the widespread importance of proper glycosylation. The condition follows an X-linked inheritance pattern, with males generally experiencing more severe manifestations than females, though some females carrying pathogenic variants show significant clinical features due to unfavourable X-inactivation patterns.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic SLC35A2 variants typically follow x-linked inheritance.
X-linked recessive: sons of a carrier mother have a 50% chance of being affected. Daughters have a 50% chance of being carriers.
UK clinical status
SLC35A2 appears on multiple NHS Genomic Medicine Service panels, reflecting its importance in diagnosing several related conditions. The gene holds green (high evidence) status on the Congenital Disorders of Glycosylation panel, DDG2P, Early Onset or Syndromic Epilepsy panel (R59), Fetal Anomalies panel (R21), Intellectual Disability panel (R29), Likely Inborn Error of Metabolism panel (R98), Malformations of Cortical Development panel, and Undiagnosed Metabolic Disorders panel. This extensive panel membership indicates strong evidence supporting SLC35A2 testing for individuals presenting with seizures, developmental delays, brain malformations, or suspected metabolic conditions, particularly when glycosylation defects are considered in the differential diagnosis.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
Why does SLC35A2 affect males and females differently?
SLC35A2 is located on the X chromosome, so males have only one copy whilst females have two. Males with a pathogenic variant typically show more severe features because they lack a backup copy. Females may be mildly affected or show significant features depending on which X chromosome is active in different cells, a process called X-inactivation.
What is glycosylation and why is it important?
Glycosylation is the process of attaching sugar chains to proteins and lipids, which allows these molecules to fold correctly and function properly. This modification affects numerous cellular processes including cell signalling, immune function, and brain development. Disrupted glycosylation can therefore cause problems in multiple organ systems.
Can SLC35A2-related conditions be detected before birth?
Some features associated with SLC35A2 variants, such as certain brain malformations, may be visible on detailed prenatal ultrasound scans. However, many neurological features only become apparent after birth. Genetic testing can be offered during pregnancy if there is a known family history or concerning ultrasound findings.