IFT81
protein-codingintraflagellar transport 81, the group of IFT-B1 complex
Gene summary
The protein encoded by this gene, together with IFT74, forms a tubulin-binding module of intraflagellar transport complex B. This module is involved in transport of tubulin within the cilium, and the encoded protein is required for ciliogenesis. Mutations in this gene are a cause of short-rib polydactyly syndromes. [provided by RefSeq, Dec 2016]
- CDV1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~94.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0033485
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0005308
Submitter: Franklin by Genoox
In an individual with ciliopathy phenotype including retinal dystrophy and intellectual disability, a homozygous deletion of five nucleotides in IFT81 gene was found http://dx.doi.org/10.1136/jmedgenet-2014-102838
Inheritance Pattern: AR
Disease ID:MONDO:0033485
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0033485
Submitter: ClinGen
*IFT81* was first reported in relation to autosomal recessive short-rib thoracic dysplasia 19 with or without polydactyly in 2016 (Duran et al., PMID: 27666822). Per criteria outlined by the ClinGen Lumping and Splitting guidelines, we found no differences in molecular mechanism, inheritance pattern or phenotypic variability. Therefore, a single disease entity, short-rib thoracic dysplasia with or without polydactyly, was curated. Seven variants (missense, nonsense, frameshift, intragenic duplication, intragenic deletion) that have been reported in 5 probands in 3 publications (PMIDs: 27666822, 27666822, 30080953) are included in this curation. The mechanism of pathogenicity is unclear. This gene-disease relationship is also supported by experimental evidence of biochemical function, with roles in the Intraflagellar Transport complex, ciliogenesis, and Hedgehog signalling (PMIDs: 22118932, 23990561, 27666822). In summary, there is moderate evidence supporting the relationship between *IFT81* and autosomal recessive short-rib thoracic dysplasia 19. This classification was approved by the ClinGen Skeletal Disorders GCEP on the meeting date March 5, 2025 (SOP Version 11).
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Genitourinary; Musculoskeletal
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 IFT81 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014055.4. 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 | 100 | 100 | ||||
| missense | 2 | 221 | 12 | 1 | 236 | |
| nonsense | 6 | 9 | 3 | 18 | ||
| start loss | 2 | 2 | ||||
| frameshift | 13 | 9 | 3 | 25 | ||
| splice donor/acceptor (+/-2bp) | 12 | 10 | 22 | |||
| Total | 19 | 32 | 239 | 112 | 1 | 403 |
Highest pathogenic variant AF is 0.00017614938
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_054774.2 | 18 | MANE Select | |
| Ensembl | ENSP00000242591.5 | 18 | MANE Select | |
| RefSeq | NP_001137251.1 | 18 | Standard | |
| RefSeq | NP_001334875.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ift81 | Danio rerio | Structure: post-vent region Quality: increased curvature abnormal |
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
- spermatogenesis
- regulation of smoothened signaling pathway
- intraciliary transport involved in cilium assembly
- intraciliary transport
- cilium assembly
Molecular Function
- protein binding
- tubulin binding
Cellular Component
- centrosome
- cilium
- intraciliary transport particle B
- motile cilium
- ciliary basal body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000242591
- Coding exons
- 18
- Length
- 94463
- Individuals with no LoFs
- 125675
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 73
- Defined
- 125748
- p
- 0.000290
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.828 | 293 | 336 | 0.873 | 0.0000173 | 4496 |
| Missense (PolyPhen) | 79 | 96.506 | 0.8186 | 1278 | ||
| Synonymous | 0.295 | 99 | 103 | 0.963 | 0.00000467 | 1132 |
| Loss of Function | 2.63 | 25 | 43.8 | 0.571 | 0.00000246 | 547 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00045 | 0.00043 | rare |
| Latino/Admixed American | 0.00039 | 0.00038 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00027 | 0.00026 | rare |
| South Asian | 0.00056 | 0.00052 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the intraflagellar transport (IFT) complex B: together with IFT74, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium. Binds tubulin via its CH (calponin-homology)-like region (PubMed:23990561). Required for ciliogenesis (PubMed:27666822, PubMed:23990561). Required for proper regulation of SHH signaling (PubMed:27666822). {ECO:0000269|PubMed:23990561, ECO:0000269|PubMed:27666822}.;
- Disease
- DISEASE: Short-rib thoracic dysplasia 19 with or without polydactyly (SRTD19) [MIM:617895]: 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:27666822}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.416
- RVIS EVS
- -0.31
- RVIS percentile EVS
- 32.06
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.137
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |