IFT172
protein-codingintraflagellar transport 172, the group of IFT-B2 complex|WD repeat domain containing
Gene summary
This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005308
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0019200
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0015229
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009964
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0018770
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014284
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0014618
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0005308
Submitter: ClinGen
*IFT172* was first reported in relation to autosomal recessive ciliopathy in 2013 by Halbritter et al. (PMID: 24140113). This condition includes abnormal cilia, skeletal anomalies (such as polydactyly and thoracic dystrophy), kidney features (such as end-stage renal disease and kidney cysts), and vision issues (including retinal dystrophy). Per criteria outlined by the ClinGen Lumping and Splitting guidelines, we found no differences in inheritance patterns, and the range of symptoms was more reflective of a spectrum than of distinct conditions. Therefore, the following disease entities have been lumped into one disease entity: autosomal recessive Bardet-Biedl syndrome (OMIM: 619471); autosomal recessive short-rib thoracic dysplasia with or without polydactyly (OMIM: 615630), and autosomal recessive retinitis pigmentosa (OMIM: 616394). 18 variants (missense, in-frame deletion, nonsense, frameshift, splicing) that have been reported in at least 14 probands in 5 publications (PMIDs: 24140113, 25492405, 33393400, 34567078, 37471416) are included in this curation. The maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is also supported by experimental evidence (zebrafish model, interaction evidence; PMIDs: 21552265, 24140113). Morpholino knockdown zebrafish exhibit abnormal ciliogenesis, cartilage anomalies, kidney cysts, and hydrocephalus. Expression of *IFT172* was shown to reduce lethality and penetrance of polydactyly in DYNC2H1 homozygous mutants, showing genetic interaction. In summary, there is definitive evidence supporting the relationship between *IFT172* and autosomal recessive ciliopathy-*IFT172*. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Kidney Cystic and Ciliopathy Disorders GCEP on the meeting date 04/23/2025 (SOP Version 11).
Inheritance Pattern: AR
Disease ID:MONDO:0023670
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014618
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014284
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014284
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal
Intervention: Endocrine
Rationale: Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial
Comments: In Short -rib thoracic dysplasia and Bardet-Biedl syndrome, renal transplantation has been desribed
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IFT172 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015662.3. 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 | 11 | 456 | 467 | |||
| missense | 4 | 6 | 957 | 66 | 3 | 1036 |
| nonsense | 24 | 34 | 2 | 60 | ||
| start loss | 0 | |||||
| frameshift | 34 | 29 | 1 | 64 | ||
| splice donor/acceptor (+/-2bp) | 2 | 46 | 12 | 60 | ||
| Total | 64 | 115 | 982 | 523 | 3 | 1687 |
Highest pathogenic variant AF is 0.000079303616
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056477.1 | 48 | MANE Select | |
| Ensembl | ENSP00000260570.3 | 48 | MANE Select | |
| RefSeq | NP_001397668.1 | 48 | Standard | |
| Ensembl | ENSP00000352443.6 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ift172 | Danio rerio | Structure: retinal cone cell Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Hedgehog signaling events mediated by Gli proteins
- Intraflagellar transport
- Cilium Assembly
- Organelle biogenesis and maintenance
Biological Process
- neural tube closure
- heart looping
- Notch signaling pathway
- smoothened signaling pathway
- brain development
Cellular Component
- cilium
- axoneme
- intraciliary transport particle B
- ciliary basal body
- sperm midpiece
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000260570
- Coding exons
- 48
- Length
- 45419
- Individuals with no LoFs
- 125578
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 170
- Defined
- 125748
- p
- 0.000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.19 | 892 | 997 | 0.894 | 0.0000567 | 11423 |
| Missense (PolyPhen) | 219 | 299 | 0.73245 | 3452 | ||
| Synonymous | 1.27 | 338 | 369 | 0.916 | 0.0000203 | 3352 |
| Loss of Function | 3.77 | 71 | 115 | 0.619 | 0.00000624 | 1265 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.0010 | notable |
| Latino/Admixed American | 0.00061 | 0.00061 | rare |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.00087 | 0.00087 | rare |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00064 | 0.00064 | rare |
| South Asian | 0.0010 | 0.0010 | notable |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for the maintenance and formation of cilia. Plays an indirect role in hedgehog (Hh) signaling, cilia being required for all activity of the hedgehog pathway (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Short-rib thoracic dysplasia 10 with or without polydactyly (SRTD10) [MIM:615630]: 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:24140113}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 71 (RP71) [MIM:616394]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:25168386}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.162
Intolerance Scores
- LoFtool
- 0.960
- RVIS EVS
- -1.96
- RVIS percentile EVS
- 1.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.706
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |