IFT52
protein-codingintraflagellar transport 52, the group of IFT-B1 complex
Gene summary
This gene encodes a conserved proline-rich protein that is a component of the intraflagellar transport-B (IFT-B) core complex. The encoded protein is essential for the integrity of the IFT-B core complex, and for biosynthesis and maintenance of cilia. Mutations in this gene are associated with ciliopathy that affects the skeleton. [provided by RefSeq, Oct 2016]
- C20orf9
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~56.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014915
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0009032
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014915
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014915
Submitter: ClinGen
*IFT52* was first reported in relation to autosomal recessive short-rib thoracic dysplasia 16 with or without polydactyly in 2016 (Zhang et al., PMID:27466190, Girisha K.M et al., PMID:26880018). Short-rib thoracic dysplasia 16 with or without polydactyly is a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a ‘trident’ appearance of the acetabular roof. It encompassess Ellis-van Creveld syndrome, Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome, and Mainzer-Saldino syndrome (MZSDS). At least 6 unique variants (missense, nonsense, frameshift) that have been reported in 4 patients in 4 publications (PMIDs: 26880018, 27466190, 30242358, 31042281) are included in this curation. This gene-disease relationship is supported by biochemical function, protein interaction, functional alteration studies, cell culture model, rescue, and zebrafish/mouse models (PMIDs: 15182712, 15930098, 31042281, 27466190, 35839863, 35704471). In summary, there is moderate evidence supporting the relationship between *IFT52* and autosomal recessive short-rib thoracic dysplasia 16 with or without polydactyly. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Skeletal Disorders GCEP on the meeting date March 5th, 2025 (SOP Version 11).
Inheritance Pattern: AR
Disease ID:MONDO:0014915
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0014915
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IFT52 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016004.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 52 | 3 | 57 | ||
| missense | 1 | 1 | 81 | 6 | 1 | 90 |
| nonsense | 2 | 1 | 1 | 4 | ||
| start loss | 0 | |||||
| frameshift | 1 | 4 | 5 | |||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 3 | 3 | 94 | 58 | 4 | 162 |
Highest pathogenic variant AF is 0.000032837426
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057088.2 | 13 | MANE Select | |
| Ensembl | ENSP00000362121.3 | 13 | MANE Select | |
| RefSeq | NP_001290387.1 | 13 | Standard | |
| RefSeq | NP_001290388.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Intraflagellar transport
- Cilium Assembly
- Organelle biogenesis and maintenance
Biological Process
- neural tube formation
- heart looping
- smoothened signaling pathway
- dorsal/ventral pattern formation
- intraciliary anterograde transport
Molecular Function
- protein C-terminus binding
Cellular Component
- centrosome
- centriole
- cilium
- intraciliary transport particle B
- motile cilium
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373030
- Coding exons
- 13
- Length
- 56366
- Individuals with no LoFs
- 125695
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 53
- Defined
- 125748
- p
- 0.000211
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.44 | 173 | 235 | 0.735 | 0.0000120 | 2911 |
| Missense (PolyPhen) | 41 | 59.489 | 0.6892 | 751 | ||
| Synonymous | 0.203 | 84 | 86.4 | 0.972 | 0.00000457 | 805 |
| Loss of Function | 2.06 | 13 | 23.9 | 0.545 | 0.00000116 | 295 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in ciliogenesis as part of a complex involved in intraflagellar transport (IFT), the bi-directional movement of particles required for the assembly, maintenance and functioning of primary cilia (PubMed:27466190). Required for the anterograde transport of IFT88 (PubMed:27466190). {ECO:0000269|PubMed:27466190}.;
- Disease
- DISEASE: Short-rib thoracic dysplasia 16 with or without polydactyly (SRTD16) [MIM:617102]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:26880018, ECO:0000269|PubMed:27466190}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- LoFtool
- 0.262
- RVIS EVS
- -0.56
- RVIS percentile EVS
- 19.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.288
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |