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IFT172
intraflagellar transport 172
IFT172 is located on the short (p) arm of chromosome 2, at band 2p23.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The IFT172 gene, located on chromosome 2, provides instructions for producing intraflagellar transport protein 172. This protein is a core component of the intraflagellar transport complex B (IFT-B), a multi-subunit assembly responsible for transporting structural and signalling molecules within cilia. Cilia are slender, antenna-like projections found on the surface of most human cells, where they detect environmental signals and coordinate developmental processes.
Disruption of IFT172 function impairs ciliary assembly and maintenance, leading to a group of inherited disorders known as ciliopathies. These conditions affect multiple organ systems that rely on proper ciliary function during development and throughout life, including the skeleton, kidneys, eyes, and brain.
What the gene does
The IFT172 protein serves as a central scaffold within the IFT-B complex, facilitating the anterograde (base-to-tip) movement of cargo along the ciliary axoneme. This transport process is essential for delivering tubulin subunits, signalling receptors, and regulatory proteins to their correct positions within the cilium. Without functional intraflagellar transport, cilia fail to assemble properly or become structurally abnormal, compromising their ability to transmit chemical and mechanical signals.
The protein coordinates with other IFT-B components and motor proteins to ensure bidirectional trafficking within the confined space of the ciliary compartment. Through its multiple protein-interaction domains, IFT172 helps organise the complex into a stable structure capable of repeated cargo-loading and unloading cycles. This activity is particularly critical during embryonic development, when ciliary signalling pathways such as Hedgehog and Wnt guide tissue patterning and organ formation.
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Chromosome location
IFT172 is located at chromosomal band 2p23.3 on the short arm of chromosome 2. The gene spans a substantial genomic region and encodes a transcript that produces a protein of 1,749 amino acids. Its position within a gene-rich region of the genome places it near other loci involved in developmental regulation.
Protein structure
The IFT172 protein is organised into distinct structural domains that mediate protein-protein interactions essential for complex assembly. The N-terminal region contains nine WD repeats (WD 1 through WD 9), which typically fold into a beta-propeller structure that serves as a platform for binding partner proteins. These WD domains span amino acids 14-559 and are interspersed throughout the first third of the protein.
The C-terminal half features six tetratricopeptide repeat (TPR) motifs (TPR 1 through TPR 6), extending from amino acid 593 to 970. TPR domains form alpha-helical structures that create grooves for recognising specific peptide sequences in other IFT components. This modular architecture allows IFT172 to act as a molecular scaffold, simultaneously engaging multiple partners to stabilise the IFT-B complex during ciliary transport.
Key variants
Pathogenic variants in IFT172 follow an autosomal recessive inheritance pattern, meaning affected individuals typically carry variants on both copies of the gene. The variant spectrum includes missense changes that disrupt protein folding, nonsense mutations leading to truncated products, and splice-site alterations that affect transcript processing. Loss-of-function variants generally correlate with more severe ciliopathy presentations, whilst some missense changes in specific domains may produce milder phenotypes.
Sample of pathogenic variants
10 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.1036C>T | p.Arg346Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Short-rib thoracic dysplasia 10 with or without polydactyly |
c.1078del | p.Glu359_Val360insTer | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome 20 |
c.1342_1343del | p.Arg448fs | Pathogenic | ★★☆☆ | Short-rib thoracic dysplasia 10 with or without polydactyly |
c.1871_1872del | p.Thr624fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome 20 |
c.2053C>T | p.Arg685Ter | Pathogenic/Likely pathogenic | ★★☆☆ | IFT172-related disorder |
c.2365C>T | p.Arg789Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 71 |
c.2456_2457del | p.Leu818_Phe819insTer | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 71 |
c.3130C>T | p.Arg1044Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 71 |
c.4519C>T | p.Arg1507Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Short-rib thoracic dysplasia 10 with or without polydactyly |
c.455_462dup | p.Val155fs | Pathogenic/Likely pathogenic | ★★☆☆ | IFT172-related disorder |
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 IFT172 cause Mainzer-Saldino syndrome, a rare autosomal recessive ciliopathy. This condition presents with a characteristic combination of features: cone-shaped epiphyses (the ends of long bones), progressive kidney disease, and retinal dystrophy leading to vision loss. Some affected individuals also experience skeletal abnormalities of the ribs and pelvis, liver fibrosis, and developmental delay.
The phenotypic spectrum can vary considerably between families, reflecting differences in the specific variants inherited and possible modifying genetic factors. Early-onset presentations may include respiratory complications from a narrow chest, whilst renal involvement can progress to end-stage kidney disease requiring dialysis or transplantation.
Inheritance pattern
Conditions caused by pathogenic IFT172 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, IFT172 holds green (high-evidence) status across multiple specialist panels that guide testing pathways. These include the Rare multisystem ciliopathy disorders panel, Skeletal ciliopathies panel, Renal ciliopathies panel, and Retinal disorders panel (R32). The gene also appears on panels for Skeletal dysplasia (R104), Thoracic dystrophies, Ophthalmological ciliopathies, Intellectual disability (R29), and Fetal anomalies (R21), reflecting the broad developmental impact of IFT172 dysfunction. This widespread inclusion supports the use of IFT172 testing when ciliopathy is suspected based on clinical or imaging findings in the NHS.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What inheritance pattern does IFT172 follow?
IFT172-related conditions follow an autosomal recessive inheritance pattern. This means an individual must inherit a pathogenic variant from both parents to develop a ciliopathy. Carriers with one variant copy typically do not show symptoms.
Can IFT172 variants affect only one organ system?
Whilst some individuals with IFT172 variants may present with predominantly renal or skeletal features early in life, the multisystem nature of ciliopathies means additional manifestations often emerge over time. Retinal changes and kidney involvement are particularly common across the phenotypic spectrum.
Is genetic testing for IFT172 available through the NHS?
Yes, IFT172 is included on multiple NHS Genomic Medicine Service gene panels with green (high-evidence) ratings. Testing is typically offered when clinical features suggest a ciliopathy, following referral to genetics services by a relevant specialist.