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IFT27
intraflagellar transport 27
IFT27 is located on the long (q) arm of chromosome 22, at band 22q12.3. Arm ratio per GRCh38 - banding schematic.
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Overview
IFT27 (intraflagellar transport 27) provides instructions for making a small protein that functions as part of the intraflagellar transport machinery, a cellular delivery system responsible for assembling and maintaining cilia. Cilia are tiny, antenna-like projections found on the surface of most human cells, where they serve diverse roles from sensing chemical signals to moving fluid across tissue surfaces.
Disruption of IFT27 can impair ciliary structure and function across multiple organ systems. Pathogenic biallelic variants in this gene have been associated with ciliopathies, a group of disorders characterised by defects in ciliary assembly or signalling. Because IFT27 variants follow autosomal recessive inheritance, carriers typically remain unaffected but may pass an altered gene copy to their children.
What the gene does
The IFT27 protein participates in intraflagellar transport, a bidirectional trafficking system that moves cargo proteins along the ciliary axoneme, the core structural scaffold of the cilium. This transport process is mediated by large protein complexes known as IFT particles, which are powered by molecular motors called kinesins and dyneins.
IFT27 is thought to act as a component of IFT complex B, which primarily mediates anterograde (base-to-tip) transport within cilia. By facilitating the delivery of structural and signalling proteins to the ciliary tip, IFT27 supports both the construction of new cilia and the ongoing maintenance of existing ciliary structures. Without functional intraflagellar transport, cilia may fail to form properly or may be unable to transduce biochemical signals effectively, disrupting cellular communication and sensory processes throughout the body.
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Chromosome location
IFT27 is located on chromosome 22 at cytogenetic band 22q12.3, a region on the long arm of chromosome 22. The gene is relatively compact, producing a messenger RNA that encodes a protein of 186 amino acids. Chromosomal rearrangements or deletions affecting this region can occasionally contribute to ciliopathy phenotypes, though most pathogenic changes are point mutations or small insertions and deletions within the gene itself.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. The IFT27 polypeptide is relatively small at 186 amino acids, and structural studies suggest it adopts a compact fold that facilitates its incorporation into larger IFT complexes. The protein's precise binding interfaces and structural motifs that mediate interaction with other intraflagellar transport components remain areas of active investigation.
Key variants
Pathogenic variants in IFT27 are predominantly loss-of-function changes, including nonsense mutations, frameshift insertions or deletions, and splice-site alterations that disrupt normal protein production. Missense variants affecting conserved residues critical for protein stability or complex assembly have also been reported. The variant spectrum reflects the autosomal recessive inheritance pattern, with affected individuals typically carrying two pathogenic alleles, one inherited from each parent.
Sample of pathogenic variants
5 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.107A>G | p.Tyr36Cys | Pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.126_130del | p.Met42fs | Pathogenic/Likely pathogenic | ★★☆☆ | IFT27-related disorders |
c.118_125del | p.Thr40fs | Pathogenic | ★☆☆☆ | not provided |
c.171del | p.Ser57fs | Pathogenic | ★☆☆☆ | not provided |
c.97C>T | p.Gln33Ter | 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
Biallelic pathogenic variants in IFT27 have been linked to ciliopathies affecting multiple organ systems. The most commonly described phenotype resembles Bardet-Biedl syndrome, a condition characterised by a combination of features that may include vision loss due to retinal degeneration, extra digits, kidney abnormalities, learning difficulties, and obesity. Other ciliopathy features such as skeletal malformations and structural brain anomalies have also been observed in individuals with IFT27 variants. The range and severity of features can vary considerably, even among individuals with the same genetic changes.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic IFT27 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, IFT27 appears on multiple green-rated gene panels, reflecting its established role in inherited conditions. These include the Bardet Biedl syndrome panel (R107), the Fetal anomalies panel (R21), and the Retinal disorders panel (R32), among others. Green classification indicates strong evidence linking the gene to the associated condition, supporting its inclusion in diagnostic testing pathways. IFT27 is also listed on panels for Ophthalmological ciliopathies, Rare multisystem ciliopathy disorders, Renal ciliopathies, and Limb disorders, underscoring the wide-ranging clinical impact of ciliary dysfunction.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does it mean to be a carrier of an IFT27 variant?
Carriers have one pathogenic variant and one normal copy of IFT27. They typically do not develop ciliopathy symptoms themselves but can pass the altered gene to their children. If both parents are carriers, each child has a 25% chance of inheriting two pathogenic variants and potentially developing a ciliopathy.
How are IFT27-related conditions diagnosed?
Diagnosis typically involves clinical evaluation of features such as retinal degeneration, kidney anomalies, or extra digits, followed by genetic testing to identify pathogenic variants in IFT27 and other ciliopathy genes. Imaging studies and specialist assessments may be used to characterise organ involvement.
Can IFT27 variants cause different severities of ciliopathy?
Yes, the clinical presentation can vary widely even among individuals with the same genetic variants. Some may have multiple severe features affecting many organ systems, while others exhibit milder or more limited manifestations. Factors influencing this variability are not fully understood.