Affinage

DYNC2LI1

Cytoplasmic dynein 2 light intermediate chain 1 · UniProt Q8TCX1

Length
351 aa
Mass
39.6 kDa
Annotated
2026-06-09
38 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DYNC2LI1 (D2LIC) is the light intermediate chain subunit of the cytoplasmic dynein-2 motor that powers retrograde intraflagellar transport (IFT) along the ciliary axoneme (PMID:11907264, PMID:12802075). It binds the dynein-2 heavy chain DYNC2H1 directly to form a core DYNC2H1-DYNC2LI1 subcomplex, one of three modules that assemble the dynein-2 holoenzyme, and this interaction is required for complex stability (PMID:11907264, PMID:29742051, PMID:34997029). Within the assembled motor the DYNC2H1-DYNC2LI1 dimer mediates contacts with the IFT-B complex (IFT54 and IFT57) that are needed for anterograde loading of dynein-2 and effective transport (PMID:36632779), and its ciliary recruitment and stability depend on other dynein-2 subunits including WDR34 and the light chain DYNLL1 (PMID:28379358, PMID:31009951). Loss of DYNC2LI1 across model organisms produces shortened or abnormally elongated cilia with bulb-like tips that accumulate IFT proteins, reflecting failed retrograde transport (PMID:12802075, PMID:19474410, PMID:26077881). In disease, pathogenic DYNC2LI1 variants disrupt DYNC2H1 and WDR60 binding and fail to rescue ciliary defects in knockout cells, while compound heterozygous variant combinations recapitulate disease; downstream, mutant cells mislocalize the Hedgehog GPCRs Smoothened and GPR161, reduce GLI3 repressor processing, and show impaired Hedgehog-dependent osteogenic differentiation, explaining the skeletal ciliopathy phenotype including short rib polydactyly syndrome (PMID:26077881, PMID:34997029, PMID:40396377).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 High

    Establishing that mammalian dynein-2 contains a dedicated light intermediate chain answered what subunits compose the retrograde ciliary motor beyond the heavy chain.

    Evidence Reciprocal co-IP, sedimentation, and immunofluorescence in mammalian cells identifying D2LIC as a DHC2/DYNC2H1 partner at the Golgi and centrosome

    PMID:11907264

    Open questions at the time
    • Stoichiometry within the holoenzyme not resolved
    • Functional role beyond binding not yet tested
  2. 2003 High

    Cross-organism work confirmed D2LIC is a bona fide retrograde IFT motor subunit and placed it functionally downstream of IFT complex A in retrograde transport.

    Evidence Flagellar copurification, fractionation and IP in Chlamydomonas; GFP live imaging and genetic epistasis with complex A mutants in C. elegans (XBX-1)

    PMID:12802074 PMID:12802075

    Open questions at the time
    • Molecular role of the LIC in motor mechanics not defined
    • How retrograde movement is initiated at ciliary tip unclear
  3. 2004 Medium

    Identifying RFX3 as a transcriptional regulator of D2lic connected ciliary gene expression control to motor abundance in ciliated cells.

    Evidence RFX3-deficient knockout mice with stunted nodal cilia and altered D2lic expression

    PMID:15121860

    Open questions at the time
    • Direct promoter binding not demonstrated
    • Relevance to non-nodal ciliated tissues unclear
  4. 2008 Medium

    Knockout in Tetrahymena clarified that dynein-2/D2LIC tunes ciliary length but is dispensable for ciliogenesis itself in some contexts.

    Evidence Targeted gene knockout with EM and cilia length measurements in Tetrahymena thermophila

    PMID:19019986

    Open questions at the time
    • Organism-specific differences from vertebrate phenotypes unexplained
    • No IFT accumulation seen, unlike other systems
  5. 2009 Medium

    Zebrafish knockdown extended the retrograde IFT requirement to vertebrate sensory cilia and photoreceptor outer segment formation.

    Evidence Morpholino knockdown with IHC, TEM showing IFT88 accumulation in swollen connecting cilia, and ERG

    PMID:19474410

    Open questions at the time
    • Morpholino off-target effects not excluded
    • Mechanism linking IFT failure to outer segment loss not detailed
  6. 2015 High

    Patient mutations established DYNC2LI1 as a skeletal ciliopathy gene and showed it is essential for dynein-2 complex stability and Hedgehog signaling.

    Evidence Whole-exome sequencing of short rib polydactyly patients with primary fibroblast complex-stability, cilia morphology, IFT accumulation, and Hedgehog reporter assays

    PMID:26077881

    Open questions at the time
    • Specific Hedgehog effectors disrupted not yet mapped
    • Variant-specific molecular consequences not dissected
  7. 2017 Medium

    Defining WDR34 as upstream of DYNC2LI1 ciliary localization ordered the assembly hierarchy of the dynein-2 complex.

    Evidence Wdr34 knockout mouse with immunofluorescence of Lic3/DYNC2LI1 ciliary localization

    PMID:28379358

    Open questions at the time
    • Direct WDR34-DYNC2LI1 contact not shown
    • Whether effect is on recruitment versus stability unresolved
  8. 2018 Medium

    Systematic interaction mapping defined the DYNC2H1-DYNC2LI1 dimer as a discrete module within the three-subcomplex architecture of dynein-2.

    Evidence Visible immunoprecipitation assay mapping all 11 dynein-2 subunit interactions

    PMID:29742051

    Open questions at the time
    • Assay performed with overexpressed subunits
    • No structural model of the dimer interface
  9. 2019 Medium

    Two studies linked DYNC2LI1 stability and function to other dynein-2 subunits and to the IFT-B machinery, explaining how the motor loads for transport.

    Evidence Dynll1 knockout mice showing co-depletion of Dync2li1 and impaired retrograde IFT; co-IP screens and KO rescue showing DYNC2H1-DYNC2LI1 contacts IFT54/IFT57

    PMID:31009951 PMID:36632779

    Open questions at the time
    • Whether IFT-B contacts are direct or bridged not resolved
    • Mechanism of anterograde dynein-2 inhibition during cargo loading unclear
  10. 2022 High

    Variant rescue experiments revealed the molecular basis of compound heterozygous disease by showing deletion variants lose DYNC2H1/WDR60 binding while missense variants retain partial function.

    Evidence DYNC2LI1-knockout cell lines with exogenous pathogenic variant expression, co-IP with DYNC2H1 and WDR60, and ciliary rescue assays

    PMID:34997029

    Open questions at the time
    • Quantitative binding affinities not measured
    • Tissue-specific variant effects not addressed
  11. 2025 High

    Connecting DYNC2LI1 variants to Hedgehog GPCR trafficking and osteogenic differentiation provided the mechanistic chain from motor defect to skeletal phenotype.

    Evidence Dync2li1-knockout mesenchymal stem cells with variant expression, ciliary SMO/GPR161 immunofluorescence, GLI3 processing assay, and osteogenic differentiation assay

    PMID:40396377

    Open questions at the time
    • Direct cargo interactions of dynein-2 with SMO/GPR161 not shown
    • Interplay between derepressed BMP signaling and Hedgehog defect not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the DYNC2H1-DYNC2LI1 dimer is structurally configured and mechanically regulated during the anterograde-to-retrograde switch at the ciliary tip remains unresolved.
  • No high-resolution structure of the DYNC2H1-DYNC2LI1 interface
  • Regulatory triggers for retrograde activation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 2 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005929 cilium 3 GO:0005794 Golgi apparatus 1 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
DYNC2H1DYNLL1IFT54IFT57WDR34WDR60
Complex memberships
cytoplasmic dynein-2 complex

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 D2LIC (DYNC2LI1) was identified as a novel 33-kDa subunit of mammalian cytoplasmic dynein 2 complex that interacts specifically with DHC2 (cDhc1b/DYNC2H1) as demonstrated by reciprocal immunoprecipitations and sedimentation assays. D2LIC colocalizes with DHC2 at the Golgi apparatus throughout the cell cycle, and upon brefeldin A-induced Golgi fragmentation, a fraction redistributes to the cytoplasm while a subset remains around the centrosome. Reciprocal co-immunoprecipitation, sedimentation assay, immunofluorescence, brefeldin A treatment Molecular biology of the cell High 11907264
2003 The Chlamydomonas D2LIC homolog copurifies with cDHC1b during flagellar isolation, dynein extraction, sucrose density centrifugation, and immunoprecipitation, confirming it is a bona fide subunit of the retrograde IFT motor. It colocalizes with cDHC1b in the basal body region and along flagella, and its localization is altered in retrograde IFT and length control mutants. Biochemical copurification, sucrose density centrifugation, immunoprecipitation, immunocytochemistry, analysis of IFT mutants Molecular biology of the cell High 12802074
2003 The C. elegans D2LIC ortholog XBX-1 localizes to the base of cilia and undergoes both anterograde and retrograde movement along axonemes. Disruption of xbx-1 results in shortened cilia with a bulb-like structure where IFT proteins accumulate, and retrograde XBX-1 movement was still detectable in complex A mutants, placing XBX-1 function downstream of complex A proteins in retrograde IFT together with CHE-3 dynein. GFP live imaging, mutant analysis, genetic epistasis with IFT complex A mutants, behavioral assays Molecular biology of the cell High 12802075
2004 RFX3 transcription factor regulates the expression of D2lic (mouse orthologue of the C. elegans IFT gene) in nodal ciliated cells, as RFX3-deficient mice exhibit stunted nodal cilia and left-right asymmetry defects. Knockout mouse analysis, gene expression studies in RFX3-deficient embryos Molecular and cellular biology Medium 15121860
2008 Targeted elimination of the D2LIC gene in Tetrahymena thermophila results in cilia that are shorter and more variable in length but are still motile with no swollen tips or IFT accumulations, demonstrating that dynein-2 (including D2LIC) contributes to ciliary length regulation but is not required for ciliogenesis in this organism. Targeted gene knockout, electron microscopy, cilia length measurements Molecular biology of the cell Medium 19019986
2009 Morpholino knockdown of the dync2-li1 subunit in zebrafish results in small eyes, kidney cysts, shortened and disorganized photoreceptor outer segments, swollen connecting cilia with IFT88 accumulation, and reduced ERG amplitudes, demonstrating that DYNC2LI1 is required for retrograde IFT and outer segment extension in vertebrate photoreceptors. Morpholino knockdown in zebrafish, immunohistochemistry, transmission electron microscopy, electroretinography Investigative ophthalmology & visual science Medium 19474410
2015 DYNC2LI1 is essential for dynein-2 complex stability; mutations in DYNC2LI1 found in short rib polydactyly syndrome patients result in variable-length and hyperelongated cilia, ciliary IFT accumulations, and impairment of Hedgehog pathway signaling in primary fibroblasts. Whole-exome sequencing, primary fibroblast analysis, cilia length measurements, IFT accumulation assays, Hedgehog pathway reporter assays Nature communications High 26077881
2017 Wdr34 is required for the ciliary localization of dynein-2 light intermediate chain Lic3 (DYNC2LI1), placing WDR34 upstream of DYNC2LI1 in dynein-2 complex assembly and ciliary localization. Wdr34 knockout mouse, immunofluorescence of Lic3 ciliary localization in mutant cells Human molecular genetics Medium 28379358
2018 The dynein-2 complex can be divided into three subcomplexes, with DYNC2H1-DYNC2LI1 forming one subcomplex. This was determined using visible immunoprecipitation assays mapping interaction modes among all 11 dynein-2 subunits. Visible immunoprecipitation (VIP) assay, co-immunoprecipitation Molecular biology of the cell Medium 29742051
2019 The DYNC2H1-DYNC2LI1 dimer from dynein-2 contributes to interactions with the IFT-B complex (specifically IFT54 and IFT57), which are required for effective intraflagellar transport and proper anterograde loading of the dynein-2 complex. Co-immunoprecipitation screening between dynein-2 and IFT-B subunits, knockout cell rescue experiments Journal of cell science Medium 36632779
2019 Germline knockout of Dynll1 (DYNLL1, a dynein-2 light chain) in mice leads to partial depletion of other CD2 subunits including Dync2li1, severely impaired retrograde intraflagellar transport, and ciliopathy-like phenotype, establishing that DYNLL1 is required for DYNC2LI1 stability within the dynein-2 holoenzyme. Germline and conditional knockout mice, western blotting for CD2 subunit levels, retrograde IFT analysis Human molecular genetics Medium 31009951
2022 Several pathogenic DYNC2LI1 deletion variants found in skeletal ciliopathy patients are compromised in their ability to interact with DYNC2H1 and WDR60. Deletion variants cannot rescue ciliary defects in DYNC2LI1-knockout cells, whereas missense variants alone can. When a deletion variant is coexpressed with a missense variant (mimicking compound heterozygosity), ciliary defects occur, demonstrating the molecular basis of disease in compound heterozygous patients. DYNC2LI1-knockout cell lines, exogenous expression of pathogenic variants, co-immunoprecipitation with DYNC2H1 and WDR60, ciliary phenotype rescue assays Scientific reports High 34997029
2025 DYNC2LI1 disease-causing variants expressed in Dync2li1-knockout mesenchymal stem cells cause defects in retrograde ciliary trafficking of Hedgehog pathway GPCRs (Smoothened and GPR161), impair Hedgehog signaling (reduced GLI3 repressor/total GLI3 ratio), and result in impaired osteogenic differentiation. Conversely, BMP signaling-driven osteogenic differentiation is derepressed in knockout cells. Dync2li1-knockout C3H10T1/2 cells, exogenous expression of pathogenic variants, immunofluorescence of ciliary GPCRs, GLI3 processing assay, osteogenic differentiation assay Journal of cell science High 40396377

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The transcription factor RFX3 directs nodal cilium development and left-right asymmetry specification. Molecular and cellular biology 175 15121860
1990 Characterization of repetitive sequences controlling phase variation of Haemophilus influenzae lipopolysaccharide. Journal of bacteriology 117 1693145
2003 XBX-1 encodes a dynein light intermediate chain required for retrograde intraflagellar transport and cilia assembly in Caenorhabditis elegans. Molecular biology of the cell 106 12802075
2003 A novel dynein light intermediate chain colocalizes with the retrograde motor for intraflagellar transport at sites of axoneme assembly in chlamydomonas and Mammalian cells. Molecular biology of the cell 94 12802074
2020 Graphitic Carbon Nitride (g-C3 N4 ): An Interface Enabler for Solid-State Lithium Metal Batteries. Angewandte Chemie (International ed. in English) 79 31851408
2002 Identification of a novel light intermediate chain (D2LIC) for mammalian cytoplasmic dynein 2. Molecular biology of the cell 72 11907264
2015 Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome. Nature communications 69 26077881
1993 Structural studies of the saccharide part of the cell envelope lipopolysaccharide from Haemophilus influenzae strain AH1-3 (lic3+). Carbohydrate research 62 8370043
1991 Molecular analysis of a complex locus from Haemophilus influenzae involved in phase-variable lipopolysaccharide biosynthesis. Molecular microbiology 60 1956282
2009 Retrograde intraflagellar transport by cytoplasmic dynein-2 is required for outer segment extension in vertebrate photoreceptors but not arrestin translocation. Investigative ophthalmology & visual science 57 19474410
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
2000 Evaluation of phase variation of nontypeable Haemophilus influenzae lipooligosaccharide during nasopharyngeal colonization and development of otitis media in the chinchilla model. Infection and immunity 54 10899860
1992 The gal locus from Haemophilus influenzae: cloning, sequencing and the use of gal mutants to study lipopolysaccharide. Molecular microbiology 44 1282642
2019 Interactions of the dynein-2 intermediate chain WDR34 with the light chains are required for ciliary retrograde protein trafficking. Molecular biology of the cell 40 30649997
2020 Exome-Based Case-Control Analysis Highlights the Pathogenic Role of Ciliary Genes in Transposition of the Great Arteries. Circulation research 37 32078439
2017 Loss of dynein-2 intermediate chain Wdr34 results in defects in retrograde ciliary protein trafficking and Hedgehog signaling in the mouse. Human molecular genetics 28 28379358
2008 Dynein-2 affects the regulation of ciliary length but is not required for ciliogenesis in Tetrahymena thermophila. Molecular biology of the cell 23 19019986
1992 Use of chromosomal gene fusions to investigate the role of repetitive DNA in regulation of genes involved in lipopolysaccharide biosynthesis in Haemophilus influenzae. Journal of bacteriology 23 1429450
2018 Biallelic mutations in DYNC2LI1 are a rare cause of Ellis-van Creveld syndrome. Clinical genetics 22 28857138
2021 Few Fixed Variants between Trophic Specialist Pupfish Species Reveal Candidate Cis-Regulatory Alleles Underlying Rapid Craniofacial Divergence. Molecular biology and evolution 21 32877534
2010 Localization of a guanylyl cyclase to chemosensory cilia requires the novel ciliary MYND domain protein DAF-25. PLoS genetics 19 21124868
1991 Phase variation of lipopolysaccharide in Haemophilus influenzae. Research in microbiology 16 1961982
2023 Multiple interactions of the dynein-2 complex with the IFT-B complex are required for effective intraflagellar transport. Journal of cell science 14 36632779
2022 Combinations of deletion and missense variations of the dynein-2 DYNC2LI1 subunit found in skeletal ciliopathies cause ciliary defects. Scientific reports 13 34997029
2018 Prenatal diagnosis of short-rib polydactyly syndrome type III or short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3) associated with compound heterozygous mutations in DYNC2H1 in a fetus. Taiwanese journal of obstetrics & gynecology 12 29458881
1992 Molecular biology of phase-variable lipopolysaccharide biosynthesis by Haemophilus influenzae. The Journal of infectious diseases 12 1588188
2020 Graphite/Graphene Composites from the Recovered Spent Zn/Carbon Primary Cell for the High-Performance Anode of Lithium-Ion Batteries. ACS omega 11 32637797
2020 Common atrium/atrioventricular canal defect and postaxial polydactyly: A mild clinical subtype of Ellis-van Creveld syndrome caused by hypomorphic mutations in the EVC gene. Human mutation 11 32906221
2019 Dynll1 is essential for development and promotes endochondral bone formation by regulating intraflagellar dynein function in primary cilia. Human molecular genetics 10 31009951
2017 Time-lapse observation and transcriptome analysis of a case with repeated multiple pronuclei after IVF/ICSI. Journal of assisted reproduction and genetics 10 28643089
2019 A new case of KIAA0753-related variant of Jeune asphyxiating thoracic dystrophy. European journal of medical genetics 7 31816441
2009 Dynein-2 and ciliogenesis in Tetrahymena. Cell motility and the cytoskeleton 7 19562737
2020 Whole-exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy. Molecular genetics & genomic medicine 5 33030252
2023 Ion Kinetics and Capacity Tailoring in Stacked Graphdiyne by Functionalization. ACS omega 3 36910975
2025 Skeletal ciliopathy variants of the dynein-2 DYNC2LI1 subunit impair osteogenic differentiation of mesenchymal stem cells. Journal of cell science 2 40396377
2023 Comparative transcriptome analysis reveals key genes and pathways related to gonad development in the sea cucumber Apostichopus japonicus. Comparative biochemistry and physiology. Part D, Genomics & proteomics 2 37769382
2023 Reanalysis of Whole-Exome Sequencing Data of an Infant with Suspected Diagnosis of Jeune Syndrome Revealed a Likely Pathogenic Variant in GRK2: A Newly Associated Gene for Jeune Syndrome Phenotype. Molecular syndromology 2 38585547
2019 [Study of genetic etiology in fetuses with severely short limbs in the first and second trimester using whole exome sequencing]. Zhonghua fu chan ke za zhi 1 31006186

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