IFT88
protein-codingintraflagellar transport 88, the group of IFT-B1 complex|Tetratricopeptide repeat domain containing
Gene summary
This gene encodes a member of the tetratrico peptide repeat (TPR) family. The encoded protein is involved in cilium biogenesis. Mutations of a similar gene in mouse can cause polycystic kidney disease. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2017]
- TTC10
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~124.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0019200
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Gastrointestinal; Neurologic; Renal
Intervention: General
Rationale: Individuals may have renal and hepatic manifestations in this reported lethal disorder; 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 IFT88 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006531.5. 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 | 3 | 79 | 5 | 87 | ||
| missense | 1 | 299 | 12 | 8 | 320 | |
| nonsense | 7 | 7 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 12 | 13 | |||
| splice donor/acceptor (+/-2bp) | 22 | 22 | ||||
| Total | 0 | 2 | 344 | 91 | 13 | 450 |
Highest pathogenic variant AF is 0.0000021988137
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006522.2 | 25 | MANE Select | |
| Ensembl | ENSP00000261632.5 | 25 | MANE Select | |
| RefSeq | NP_001305420.1 | 24 | Standard | |
| RefSeq | NP_001305422.1 | 26 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ift88 | Danio rerio | Structure: neuromast hair cell Quality: absent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endochondral Ossification
- Hedgehog signaling events mediated by Gli proteins
- Intraflagellar transport
- Cilium Assembly
- Organelle biogenesis and maintenance
Biological Process
- kidney development
- intraciliary transport involved in cilium assembly
- inner ear receptor cell stereocilium organization
- cilium assembly
- regulation of cilium assembly
Molecular Function
- protein binding
- kinesin binding
Cellular Component
- centrosome
- centriole
- cilium
- intraciliary transport particle B
- motile cilium
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000319980
- Coding exons
- 26
- Length
- 124919
- Individuals with no LoFs
- 125668
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 80
- Defined
- 125748
- p
- 0.000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.335 | 394 | 413 | 0.954 | 0.0000201 | 5478 |
| Missense (PolyPhen) | 65 | 83.894 | 0.77479 | 1115 | ||
| Synonymous | 0.982 | 122 | 137 | 0.893 | 0.00000673 | 1456 |
| Loss of Function | 3.21 | 25 | 49.3 | 0.507 | 0.00000245 | 683 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00066 | 0.00062 | rare |
| Latino/Admixed American | 0.00017 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00028 | 0.00027 | rare |
| Finnish | 0.000094 | 0.000092 | rare |
| European (Non-Finnish) | 0.00043 | 0.00040 | rare |
| South Asian | 0.00032 | 0.00029 | rare |
| Other | 0.00020 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in primary cilium biogenesis. Also involved in autophagy since it is required for trafficking of ATG16L and the expansion of the autophagic compartment. {ECO:0000250|UniProtKB:Q61371}.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.635
- RVIS EVS
- -0.26
- RVIS percentile EVS
- 34.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.817
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |