Affinage

Showing DYNC2I2 — WDR34 is a alias.

DYNC2I2

Cytoplasmic dynein 2 intermediate chain 2 · UniProt Q96EX3

Length
536 aa
Mass
57.8 kDa
Annotated
2026-06-09
21 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DYNC2I2 (WDR34) encodes a WD40-repeat dynein intermediate chain that is an integral subunit of the dynein-2 retrograde intraflagellar transport (IFT) motor, where it associates with the IFT dynein heavy chain, the light intermediate chain, and the LC8 dynein light chain (PMID:17895364). It concentrates around centrioles and basal bodies and shows axonemal staining, and its peri-basal-body localization depends on the intact motor complex, since loss of the heavy chain or light intermediate chain redistributes it away from the basal-body region (PMID:17895364, PMID:24183451). Reciprocally, DYNC2I2 is itself required to assemble the dynein-2 complex at the ciliary base, organizing the recruitment of multiple dynein subunits there (PMID:24989795). Through this assembly role, DYNC2I2 supports axoneme initiation and extension, proper distribution of IFT complex-B proteins within cilia, transition zone integrity, and Hedgehog signaling, and patient mutations that disrupt these functions cause skeletal ciliopathies including Jeune asphyxiating thoracic dystrophy and short-rib polydactyly syndrome (PMID:24183451, PMID:36268591).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2007 High

    Established that the WDR34 ortholog is a bona fide intermediate chain of the retrograde IFT dynein motor rather than a free-standing protein, by defining its physical partners and showing its localization depends on the motor complex.

    Evidence Flagellar matrix fractionation, co-immunoprecipitation, and immunofluorescence in Chlamydomonas IFT dynein mutants

    PMID:17895364

    Open questions at the time
    • Stoichiometry and structural arrangement within the dynein-2 complex not resolved
    • Direct binding interfaces between FAP133 and each subunit not mapped
    • Findings in alga; mammalian complex composition not yet tested here
  2. 2013 Medium

    Linked WDR34 to human disease and placed the mammalian protein at centrioles/basal bodies, while raising a possible bridge between cytoplasmic dynein-1 and IFT dynein-2 via a shared light chain.

    Evidence Exome/targeted sequencing of patients, immunofluorescence localization, and in vitro co-IP with DYNLL1 in mammalian cells

    PMID:24183451

    Open questions at the time
    • DYNLL1 interaction rests on a single in vitro co-IP without reciprocal or functional validation
    • Functional significance of a dynein-1/dynein-2 link not established
    • Mutation-to-phenotype mechanism not yet defined
  3. 2014 Medium

    Demonstrated that WDR34 is causally required for assembling the IFT dynein complex at the flagellar base, by showing its loss mislocalizes the heavy chains and light intermediate chain.

    Evidence RNAi knockdown of the DIC5 ortholog in Trypanosoma brucei with immunofluorescence and western blot readouts of dynein subunit localization

    PMID:24989795

    Open questions at the time
    • Single organism and lab
    • Whether the assembly role is direct or via complex stabilization unresolved
    • No biochemical reconstitution of the assembly step
  4. 2022 High

    Connected specific patient mutations to defined molecular defects, showing WDR34 is required for multiple aspects of dynein-2 function and that distinct alleles produce distinct phenotypic outcomes.

    Evidence Patient-allele complementation in WDR34-knockout cells with quantitative proteomics, IFT-B and transition-zone immunofluorescence, and Hedgehog reporter assays

    PMID:36268591

    Open questions at the time
    • Mechanistic basis for allele-specific phenotypic differences not fully resolved
    • How transition zone integrity is mechanistically maintained by dynein-2 not defined
    • Structural consequences of individual mutations on complex assembly not directly visualized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dynein-2 complex is assembled at the basal body at the molecular level and whether the dynein-1/dynein-2 link via a shared light chain is functionally meaningful remain open.
  • No structural model of WDR34 within the assembled dynein-2 motor
  • Functional role of the DYNLL1 interaction untested in vivo
  • Mechanism coupling dynein-2 to transition zone integrity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005815 microtubule organizing center 2 GO:0005929 cilium 2
Pathway
R-HSA-1643685 Disease 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-162582 Signal Transduction 1
Partners
DYNC2H1DYNLL1
Complex memberships
dynein-2 / IFT retrograde dynein complex

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Chlamydomonas FAP133 (ortholog of WDR34/DYNC2I2) is a WD-repeat dynein intermediate chain that associates with the IFT dynein heavy chain DHC1b, the light intermediate chain D1bLIC, and the LC8 dynein light chain, forming part of the retrograde IFT dynein complex. FAP133 localizes to the peri-basal body region and in punctate structures along flagella. In the absence of DHC1b or D1bLIC, FAP133 fails to localize at the peri-basal body region and instead concentrates near the cell center, demonstrating its localization depends on the motor complex. Biochemical fractionation of flagellar matrix proteins, co-immunoprecipitation, immunofluorescence localization in IFT mutant strains Journal of cell science High 17895364
2013 WDR34 (DYNC2I2) mutations cause Jeune asphyxiating thoracic dystrophy. WDR34 concentrates around centrioles and basal bodies in mammalian cells and also shows axonemal staining. WDR34 co-immunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, suggesting a potential link between cytoplasmic dynein-1 and IFT dynein-2 motors. Exome sequencing and targeted NGS for mutation identification; immunofluorescence for subcellular localization; co-immunoprecipitation for DYNLL1 interaction; 3D protein modeling American journal of human genetics Medium 24183451
2014 In Trypanosoma brucei, the DIC5 (FAP133/WDR34/DYNC2I2) ortholog is required for the localization of dynein heavy chains DHC2.1 and DHC2.2, and the light intermediate chain DLI1, to the base of the flagellum. In the absence of DIC5, these components fail to localize correctly, establishing DIC5 as essential for assembly of the IFT dynein complex at the flagellar base. RNAi knockdown of DIC5 in Trypanosoma brucei; immunofluorescence and western blot to assess localization of dynein complex components in knockdown cells Molecular biology of the cell Medium 24989795
2022 Disease-associated WDR34 (DYNC2I2) mutations in Jeune syndrome, short-rib polydactyly syndrome, and asphyxiating thoracic dysplasia lead to diverse impacts including altered dynein-2 complex assembly, defects in axoneme initiation and extension, mislocalization of IFT complex-B proteins, disruption of transition zone integrity, and impaired Hedgehog signalling. Different mutations produce distinct phenotypic spectra, revealing that WDR34 is required for multiple aspects of dynein-2 function and ciliary transport. Stable expression of WDR34 patient mutations in WDR34-knockout cells; quantitative proteomics; immunofluorescence for IFT-B localization and transition zone markers; Hedgehog signaling reporter assays Journal of cell science High 36268591

Source papers

Stage 0 corpus · 21 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Mutations in the gene encoding IFT dynein complex component WDR34 cause Jeune asphyxiating thoracic dystrophy. American journal of human genetics 93 24183451
2007 Chlamydomonas FAP133 is a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Journal of cell science 82 17895364
1997 dic(5;17): a recurring abnormality in malignant myeloid disorders associated with mutations of TP53. Genes, chromosomes & cancer 52 9365836
2013 WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar transport in cilia. Molecular biology of the cell 43 23864713
2014 The intraflagellar transport dynein complex of trypanosomes is made of a heterodimer of dynein heavy chains and of light and intermediate chains of distinct functions. Molecular biology of the cell 31 24989795
2009 Malignant granular cell tumor: case report with a novel karyotype and review of the literature. Annals of diagnostic pathology 26 20637434
2008 Further evidence for a relationship between the 5p15 chromosome region and the oculoauriculovertebral anomaly. American journal of medical genetics. Part A 26 18792983
1995 Acute promyelocytic leukaemia (M3): relapse with acute myeloblastic leukaemia (M2) and dic(5;17) (q11;p11). American journal of hematology 24 7832190
1996 Loss of the chromosomal region 5q11-q31 in the myeloid cell line HL-60: characterization by comparative genomic hybridization and fluorescence in situ hybridization. Genes, chromosomes & cancer 18 8721684
1990 A cytogenetic study of male breast cancer. Cancer genetics and cytogenetics 18 2162731
1994 Cytogenetic triclonality in acute myeloid leukemia: a morphologic, immunologic and in situ hybridization study. Cancer genetics and cytogenetics 15 8143281
2000 Karyotypic findings in two cases of male breast cancer. Cancer genetics and cytogenetics 14 11063806
2022 Disease-associated mutations in WDR34 lead to diverse impacts on the assembly and function of dynein-2. Journal of cell science 8 36268591
2021 High Throughput Transcriptome Data Analysis and Computational Verification Reveal Immunotherapy Biomarkers of Compound Kushen Injection for Treating Triple-Negative Breast Cancer. Frontiers in oncology 8 34604090
2013 De novo unbalanced translocation resulting in monosomy for distal 5p (5p14.1 → pter) and 14q (14q32.31 → qter) associated with fetal nuchal edema, microcephaly, intrauterine growth restriction, and single umbilical artery: prenatal diagnosis and molecular cytogenetic characterization. Taiwanese journal of obstetrics & gynecology 7 24075381
2009 Dynein-2 and ciliogenesis in Tetrahymena. Cell motility and the cytoskeleton 7 19562737
2011 New recurrent chromosome alterations in patients with multiple myeloma and plasma cell leukemia. Cytogenetic and genome research 2 21734361
2023 An uninformative NIPT as an early indicator of cri-du-chat due to a chromosomal 5;18 translocation-An atypical presentation of a rare cytogenetic phenomenon. Clinical case reports 1 37529133
1999 Cri du chat and Turner syndrome features in a newborn girl with an unbalanced 45,X,psu dic(5;X)(p15.2;p22.1) karyotype: FISH and replication banding studies. Annales de genetique 1 10434125
2026 A Rare Case of Prenatal Short-Rib Thoracic Dysplasia 11 Subtype With Compound Heterozygous Variants in the DYNC2I2 Gene: Presenting Polydactyly and Shortened Limbs. Clinical case reports 0 41503593
2026 3D-printed dictamni-calcium silicate scaffolds modulate the osteoimmune microenvironment and enhance macrophage-derived exosomal miR-21 signaling in vascularized bone regeneration. Journal of nanobiotechnology 0 42098777

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