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SLC4A11
solute carrier family 4 member 11
SLC4A11 is located on the short (p) arm of chromosome 20, at band 20p13. Arm ratio per GRCh38 - banding schematic.
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Overview
SLC4A11 encodes solute carrier family 4 member 11, a membrane transport protein that plays an essential role in maintaining tissue hydration and ion balance. The protein is particularly important in the corneal endothelium, the innermost cell layer of the cornea, where it helps regulate fluid movement to keep the cornea clear and transparent. SLC4A11 also functions in the inner ear, contributing to the ionic environment necessary for normal hearing.
Pathogenic variants in SLC4A11 disrupt the protein's transport function, leading to fluid accumulation in the cornea and potentially affecting inner ear structures. These variants are inherited in an autosomal recessive manner, meaning individuals must inherit altered copies from both parents to develop clinical features. The gene is recognised in clinical genetics for its association with corneal dystrophies and hearing impairment.
What the gene does
The SLC4A11 protein functions as a membrane transporter, facilitating the movement of ions and water across cell membranes. Whilst it belongs to the solute carrier family 4, which typically includes bicarbonate transporters, research suggests SLC4A11 may operate through a distinct mechanism involving borate transport or ammonia-hydroxide exchange, though its precise biochemical role continues to be investigated.
In the corneal endothelium, SLC4A11 helps maintain the cornea's deturgescent state by regulating fluid balance. The corneal endothelium actively pumps fluid out of the corneal stroma, preventing swelling and preserving transparency. When SLC4A11 function is compromised, this regulatory process fails, leading to corneal oedema and reduced visual acuity. The protein's expression in the inner ear similarly supports the ionic gradients required for proper auditory signal transduction, explaining why some individuals with SLC4A11 variants experience sensorineural hearing loss alongside corneal abnormalities.
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Chromosome location
SLC4A11 is located on the short arm of chromosome 20 at position 20p13. The gene spans approximately 20 kilobases of genomic DNA and contains 17 exons that encode the mature protein. This chromosomal region is gene-dense, containing several other genes involved in diverse cellular processes, but SLC4A11 pathogenic variants specifically affect corneal and auditory tissues due to the protein's expression pattern and functional requirements in these cell types.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. The SLC4A11 protein consists of 875 amino acids and is predicted to contain multiple transmembrane segments characteristic of membrane transport proteins. Structural modelling suggests the protein adopts a conformation that allows it to span the cell membrane repeatedly, creating a channel or pore through which ions and small molecules can pass. The transmembrane regions are thought to form the functional core of the transporter, whilst intracellular and extracellular loops may contribute to substrate recognition and regulatory interactions.
Key variants
Pathogenic variants in SLC4A11 encompass missense changes, nonsense mutations, and small deletions that disrupt protein function. Missense variants affecting predicted transmembrane regions or functionally critical residues can impair the protein's transport activity, whilst nonsense and frameshift variants typically result in premature termination and loss of function. The severity and specific features of associated conditions may vary depending on the nature and location of the variants, with some genotypes correlating with earlier onset or more pronounced corneal involvement.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
SLC4A11 pathogenic variants cause a spectrum of corneal dystrophies characterised by progressive corneal clouding and vision deterioration. Congenital hereditary endothelial dystrophy (CHED) presents in early childhood with bilateral corneal oedema, nystagmus, and visual impairment. A later-onset form, Fuchs endothelial corneal dystrophy, can also result from SLC4A11 variants, typically manifesting in adulthood with gradual corneal thickening and reduced vision.
Some individuals with SLC4A11 variants experience Harboyan syndrome, which combines corneal dystrophy with progressive sensorineural hearing loss. The hearing impairment may develop in childhood or later in life, and its severity varies among affected individuals. These conditions are inherited in an autosomal recessive pattern, requiring pathogenic variants in both gene copies for clinical manifestation.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic SLC4A11 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
SLC4A11 is recognised on multiple NHS Genomic Medicine Service gene panels, reflecting its clinical significance in inherited eye and hearing disorders. The gene holds green classification status on the Corneal abnormalities panel, the Corneal dystrophy panel (R262), the DDG2P developmental disorders panel, and the Monogenic hearing loss panel (R67). This inclusion indicates that SLC4A11 testing is supported within the NHS for individuals presenting with relevant clinical features, and that the gene-condition associations are well-established in clinical genetics practice.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does autosomal recessive inheritance mean for SLC4A11?
Autosomal recessive inheritance means an individual must inherit a pathogenic variant in SLC4A11 from both parents to develop symptoms. Carriers, who have one altered copy and one typical copy, generally do not experience corneal or hearing problems but can pass the variant to their children.
Can SLC4A11 variants affect only the eyes or only hearing?
Most individuals with SLC4A11 pathogenic variants have corneal involvement, whilst hearing loss is present in a subset of cases, particularly in Harboyan syndrome. The presence and severity of hearing impairment can vary even among individuals with the same variants.
Is genetic testing for SLC4A11 available on the NHS?
Yes, SLC4A11 is included on NHS gene panels for corneal dystrophies and monogenic hearing loss. Testing may be offered through specialist ophthalmology or audiology genetics services when clinical features suggest an inherited corneal or auditory condition.