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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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IFT46
intraflagellar transport 46
Chromosome 11 · 11q23.3
NCBI Gene: 56912Ensembl: ENSG00000118096.10HGNC: HGNC:26146UniProt: Q9NQC8
32PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
intraciliary transport particle Aprotein bindingcytoplasmcilium assemblypsoriasiscystprimary ciliary dyskinesiaciliopathy
✦AI Summary

IFT46 is a core component of the intraflagellar transport (IFT) complex B, essential for cilium assembly, maintenance, and function 1. As part of the IFT machinery, IFT46 transports proteins along the axoneme to enable cilia biogenesis and proper ciliary structure 2. IFT46 specifically mediates ciliary import of outer dynein arms through direct binding to the ODA16 adaptor protein 34, with Arl3-mediated ODA16 release regulating this transport process 3. Beyond ciliogenesis, IFT46 regulates autophagy flux and epithelial-mesenchymal transition through the Limk2 signaling axis 5. IFT46 is preferentially expressed in early hypertrophic chondrocytes and plays a role in skeletogenesis 6. Clinically, IFT46 deficiency causes multiple ciliopathy-related pathologies including renal cysts, pericardial edema, and left-right axis patterning defects 15. SARS-CoV-2 ORF10 impairs cilia by triggering IFT46 degradation via CUL2ZYG11B-mediated ubiquitination, potentially explaining anosmia and ageusia in COVID-19 7. These findings establish IFT46 as critical for both ciliary structure maintenance and extraciliary autophagy-dependent cellular processes relevant to polycystic kidney disease and respiratory dysfunction.

Sources cited
1
IFT46 is a core IFT complex B protein required for cilium formation and essential for vertebrate ciliary development; ift46 knockdown causes kidney cysts, pericardial edema, and left-right axis patterning defects
PMID: 25722189
2
IFT46 is required for cilium formation and maintenance during vertebrate embryonic development by transporting proteins along the axoneme
PMID: 37363725
3
IFT46 directly binds ODA16 to link outer dynein arms to the IFT machinery; Arl3 mediates ODA16 release from IFT46 through allosteric mechanisms
PMID: 39880089
4
IFT46 and ODA16 interact to facilitate ciliary import of preassembled outer dynein arms in the IFT system
PMID: 32239748
5
IFT46 (mIFT46) is located in the primary cilium of chondrocytes, preferentially expressed in early hypertrophic chondrocytes, and plays a role in skeletogenesis; IFT46 knockdown affects early embryonic development
PMID: 17720815
6
SARS-CoV-2 ORF10 enhances CUL2ZYG11B E3 ligase activity to cause ubiquitination and proteasome-mediated degradation of IFT46, impairing cilia biogenesis and causing cilia dysfunction
PMID: 35674692
7
IFT46 regulates autophagy flux and controls partial epithelial-mesenchymal transition through Limk2 regulation; IFT46 deficiency causes renal cyst formation through impaired autophagy and enhanced Limk2
PMID: 41680856
Disease Associationsⓘ20
psoriasisOpen Targets
0.18Weak
cystOpen Targets
0.04Suggestive
primary ciliary dyskinesiaOpen Targets
0.03Suggestive
ciliopathyOpen Targets
0.02Suggestive
Polycystic kidney dysplasiaOpen Targets
0.01Suggestive
Polycystic Kidney DiseaseOpen Targets
0.01Suggestive
diabetes mellitusOpen Targets
0.01Suggestive
obesityOpen Targets
0.01Suggestive
cystic kidney diseaseOpen Targets
0.00Suggestive
dementiaOpen Targets
0.00Suggestive
genetic disorderOpen Targets
0.00Suggestive
Beckwith-Wiedemann syndromeOpen Targets
0.00Suggestive
breast cancerOpen Targets
0.00Suggestive
HydrocephalusOpen Targets
0.00Suggestive
situs inversusOpen Targets
0.00Suggestive
COVID-19Open Targets
0.00Suggestive
Axenfeld-Rieger syndromeOpen Targets
0.00Suggestive
Kidney CystOpen Targets
0.00Suggestive
ependymomaOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
IFT140Protein interaction100%IFT27Protein interaction100%IFT38Protein interaction100%IFT54Protein interaction100%IFT122Protein interaction100%IFT20Protein interaction99%
Tissue Expression6 tissues
Ovary
100%
Heart
98%
Brain
77%
Lung
49%
Liver
48%
Bone Marrow
32%
Gene Interaction Network
Click a node to explore
IFT46IFT140IFT27IFT38IFT54IFT122IFT20
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9NQC8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.70LoF Tolerant
pLIⓘ
0.04Tolerant
Observed/Expected LoF0.46 [0.31–0.70]
RankingsWhere IFT46 stands among ~20K protein-coding genes
  • #11,528of 20,598
    Most Researched32
  • #5,378of 17,882
    Most Constrained (LOEUF)0.70
Genes detectedIFT46
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PMID: 37363725
Front Cell Dev Biol · 2023
1.00
2
Knockdown of the intraflagellar transport protein IFT46 stimulates selective gene expression in mouse chondrocytes and affects early development in zebrafish.
PMID: 17720815
J Biol Chem · 2007
0.90
3
Integrative in silico and biochemical analyses demonstrate direct Arl3-mediated ODA16 release from the intraflagellar transport machinery.
PMID: 39880089
J Biol Chem · 2025
0.80
4
IFT46 plays an essential role in cilia development.
PMID: 25722189
Dev Biol · 2015
0.70
5
SARS-CoV-2 ORF10 impairs cilia by enhancing CUL2ZYG11B activity.
PMID: 35674692
J Cell Biol · 2022
0.60