Affinage

DYNC2I1

Cytoplasmic dynein 2 intermediate chain 1 · UniProt Q8WVS4

Length
1066 aa
Mass
122.6 kDa
Annotated
2026-06-09
13 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DYNC2I1/WDR60 is a dynein-2-specific intermediate chain that is essential for retrograde intraflagellar transport (IFT) and ciliary function (PMID:23864713, PMID:36461782). Within the dynein-2 motor it nucleates a dedicated subcomplex by directly binding the TCTEX1D2–DYNLT1/DYNLT3 dimer, distinct from the DYNC2H1–DYNC2LI1 and WDR34-containing modules; loss of WDR60 abolishes assembly of the dynein-2 complex and severely disrupts retrograde ciliary protein trafficking, with the TCTEX1D2 interaction playing an auxiliary role (PMID:29742051). WDR60 localizes to the base of the primary cilium and is required for ciliogenesis and proper Hedgehog pathway execution: loss-of-function causes aberrant GLI2 accumulation at the centrosome/basal body and downregulation of Sonic Hedgehog signaling in vivo, consistent with its physical interaction with the IFT-B component IFT88 (PMID:23910462, PMID:37228654). Beyond cilia, WDR60 localizes to the neuronal microtubule-organizing center and controls the multipolar-to-bipolar transition during cortical neuronal migration through effects on microtubule acetylation/stability, a defect rescued by an acetylation-mimicking α-tubulin K40Q mutant (PMID:33436552).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2013 Medium

    Established WDR60 as a required factor for ciliogenesis and Hedgehog signaling, linking the gene to a defined human ciliopathy phenotype.

    Evidence Immunofluorescence in human chondrocytes and analysis of patient fibroblasts carrying loss-of-function mutations

    PMID:23910462

    Open questions at the time
    • Mechanism connecting WDR60 loss to GLI2 mislocalization not resolved
    • Did not define the molecular complex WDR60 acts within
  2. 2013 High

    Identified the WDR60 ortholog as an integral retrograde IFT dynein component, establishing its role in retrograde transport at the biochemical and genetic level.

    Evidence Co-purification from Chlamydomonas flagella with dynein-1b intermediate chain FAP133 and LC8; RNAi knockdown in planaria with ciliary phenotyping

    PMID:23864713

    Open questions at the time
    • Used invertebrate/algal orthologs rather than human protein
    • Did not map the human dynein-2 subcomplex architecture
  3. 2018 High

    Resolved the architecture of the dynein-2 motor, showing WDR60 forms a discrete subcomplex with TCTEX1D2–DYNLT1/DYNLT3 and is structurally required for complex assembly and retrograde trafficking.

    Evidence Visible immunoprecipitation interaction mapping, CRISPR/Cas9 knockout of WDR60 and TCTEX1D2, and interaction-deficient rescue with trafficking assays

    PMID:29742051

    Open questions at the time
    • No structural model of the assembled subcomplex
    • Cargo-adapter interactions of WDR60 not yet defined
  4. 2021 Medium

    Revealed a non-ciliary function for WDR60 at the neuronal MTOC controlling microtubule acetylation and neuronal migration, broadening its role beyond IFT.

    Evidence shRNA knockdown by in utero electroporation in mouse cortex with MTOC localization and rescue by α-tubulin K40Q

    PMID:33436552

    Open questions at the time
    • Molecular mechanism linking WDR60 to tubulin acetylation unknown
    • Whether this role depends on dynein-2 complex assembly unclear
  5. 2022 Medium

    Demonstrated functional specificity of the intermediate chains, showing WDR60 serves dynein-2/IFT exclusively while DYCI-1 serves dynein-1/axonal transport.

    Evidence Mutational analysis of wdr-60 and dyci-1 alleles in C. elegans with IFT and axonal transport assays

    PMID:36461782

    Open questions at the time
    • Performed in C. elegans; human specificity inferred
    • Does not address overlap with the MTOC/migration role
  6. 2023 Medium

    Defined differential IFT adapter interactions, showing WDR60 binds IFT-B component IFT88 and that its deficiency downregulates SHH signaling in vivo.

    Evidence Co-immunoprecipitation from mouse embryo tissue and Wdr60 hypomorph mouse with RNAseq/qRT-PCR of SHH pathway components

    PMID:37228654

    Open questions at the time
    • Single Co-IP without reciprocal/structural validation of IFT88 binding
    • Direct cargo specificity for retrograde transport not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How WDR60 mechanistically couples retrograde IFT cargo selection to Hedgehog output, and how its ciliary versus MTOC/microtubule-acetylation roles are coordinated, remain open.
  • No structural model of WDR60 within the assembled dynein-2 motor
  • Mechanism of WDR60-dependent tubulin acetylation unknown
  • Direct retrograde cargoes of WDR60 not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005929 cilium 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-162582 Signal Transduction 2 R-HSA-1266738 Developmental Biology 1
Partners
DYNLT1DYNLT3IFT88TCTEX1D2
Complex memberships
WDR60–TCTEX1D2–DYNLT1/DYNLT3 subcomplexdynein-2 (cytoplasmic dynein 2) motor complex

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 WDR60 (DYNC2I1) localizes at the base of the primary cilium in human chondrocytes, and loss-of-function mutations cause defects in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome/basal body in the absence of an obvious axoneme, establishing WDR60 as required for ciliogenesis and proper Hedgehog pathway execution. Immunofluorescence localization in wild-type human chondrocytes; analysis of fibroblasts from affected individuals with WDR60 mutations (loss-of-function). American journal of human genetics Medium 23910462
2013 The Chlamydomonas/planarian ortholog of WDR60 (FAP163/WD60) is an integral component of the retrograde IFT dynein complex: it co-purifies with dynein-1b intermediate chain FAP133 and the LC8 dynein light chain, is present in the flagellar matrix, and is trafficked by IFT. RNAi knockdown in planaria causes severe ciliary assembly defects with IFT particle accumulation, demonstrating that WD60 is absolutely required for retrograde IFT. Biochemical co-purification from Chlamydomonas flagella; RNAi knockdown in planaria with phenotypic analysis (ciliary morphology, IFT particle accumulation, beat frequency). Molecular biology of the cell High 23864713
2018 WDR60 forms a distinct dynein-2 subcomplex (WDR60–TCTEX1D2–DYNLT1/DYNLT3) that is separate from the DYNC2H1-DYNC2LI1 and WDR34-DYNLL1/DYNLL2-DYNLRB1/DYNLRB2 subcomplexes. WDR60 directly interacts with the TCTEX1D2-DYNLT1/DYNLT3 dimer. WDR60 knockout causes severe defects in retrograde ciliary protein trafficking and failed assembly of the dynein-2 complex; a WDR60 mutant lacking TCTEX1D2-binding partially restores retrograde trafficking, showing WDR60 plays a major structural and functional role while TCTEX1D2 plays an auxiliary role. Visible immunoprecipitation (VIP) assay to map interaction modes among dynein-2 subunits; CRISPR/Cas9 knockout of WDR60 and TCTEX1D2; rescue experiments with interaction-deficient WDR60 mutant; ciliary trafficking assays. Molecular biology of the cell High 29742051
2022 In C. elegans, WDR-60 (the WDR60 ortholog) is the dynein-2-specific intermediate chain required for intraflagellar transport (IFT), while DYCI-1 is the dynein-1-specific intermediate chain required for retrograde axonal transport of synaptic vesicles. Loss of wdr-60 impairs IFT without affecting axonal transport, establishing functional specificity of the two intermediate chains. Mutational analysis of wdr-60 and dyci-1 alleles in C. elegans with IFT and axonal transport assays. Genes to cells Medium 36461782
2021 WDR60 localizes to the microtubule-organizing center (MTOC) in neurons and is required for the multipolar-to-bipolar transition of migrating cortical neurons. Knockdown impairs microtubule organization and neuronal migration; this migration defect is rescued by an acetylation-mimicking α-tubulin mutant (K40Q), establishing a non-ciliary role for WDR60 in controlling microtubule acetylation/stability at the MTOC. shRNA knockdown in embryonic mouse brain (in utero electroporation); immunofluorescence for MTOC localization; rescue with α-TubulinK40Q. Cell death & disease Medium 33436552
2023 WDR60 interacts with IFT88 (an IFT-B component) by co-immunoprecipitation, whereas WDR34 interacts with both IFT88 and IFT140 (an IFT-A component), revealing differential cargo/adapter interactions within the dynein-2 complex. WDR60 deficiency in mouse embryos downregulates Sonic Hedgehog (SHH) signaling, demonstrating a role in SHH pathway promotion. Co-immunoprecipitation (CO-IP) from mouse embryo tissue; Wdr60 piggyBac hypomorph mouse model with RNAseq and qRT-PCR of SHH pathway components. Frontiers in cell and developmental biology Medium 37228654

Source papers

Stage 0 corpus · 13 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Short-rib polydactyly and Jeune syndromes are caused by mutations in WDR60. American journal of human genetics 98 23910462
2018 Interaction of WDR60 intermediate chain with TCTEX1D2 light chain of the dynein-2 complex is crucial for ciliary protein trafficking. Molecular biology of the cell 54 29742051
2013 WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar transport in cilia. Molecular biology of the cell 43 23864713
1997 Spondylocostal dysostosis associated with a 46, XX,+15,dic(6;15)(q25;q11.2) translocation. Clinical dysmorphology 12 9354844
2017 Expanding the phenotype associated with biallelic WDR60 mutations: Siblings with retinal degeneration and polydactyly lacking other features of short rib thoracic dystrophies. American journal of medical genetics. Part A 8 29271569
2014 Delineation variable genotype/phenotype correlations of 6q27 terminal deletion derived from dic(6;18)(q27;p10). Molecular cytogenetics 7 25426168
2022 Dynein intermediate chains DYCI-1 and WDR-60 have specific functions in Caenorhabditis elegans. Genes to cells : devoted to molecular & cellular mechanisms 6 36461782
2023 Deficiency of Wdr60 and Wdr34 cause distinct neural tube malformation phenotypes in early embryos. Frontiers in cell and developmental biology 3 37228654
2021 SRPS associated protein WDR60 regulates the multipolar-to-bipolar transition of migrating neurons during cortical development. Cell death & disease 3 33436552
2022 A novel WDR60 variant contributes to a late diagnosis of Jeune asphyxiating thoracic dystrophy in a Chinese patient: A case report. Clinical case reports 1 36381051
2004 Characterization of psu dic(6;5)(p21.3;q13) with reverse chromosome painting in a patient with secondary myelodysplastic syndrome following treatment for multiple myeloma. Cancer genetics and cytogenetics 1 14697641
2026 Prenatal Diagnosis of Short Rib-Polydactyly Syndrome (SRPS), DYNC2I1-Related: Identification of a Novel Homozygous Missense Variant by Clinical Exome Sequencing. Clinical case reports 0 42256993
2025 Ciliogenesis in pancreatic neuroendocrine tumors: insight into the role of WDR60. Endocrine-related cancer 0 41269779

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