Affinage

DRC1

Cornulin · UniProt Q9UBG3

Length
495 aa
Mass
53.5 kDa
Annotated
2026-06-09
20 papers in source corpus 5 papers cited in narrative 5 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

DRC1 (CCDC164) encodes an essential structural subunit of the axonemal nexin-dynein regulatory complex (N-DRC), required for N-DRC assembly and dynein motor regulation in motile cilia and sperm flagella across Chlamydomonas and humans (PMID:23354437). Loss of DRC1 disrupts N-DRC integrity and impairs ciliary and flagellar motility, with flagellar damage being more severe than ciliary defects: in mouse models DRC1 absence causes complete axoneme structural disorder in flagella while cilia are shortened but comparatively preserved (PMID:34169321). DRC1 deficiency also destabilizes other N-DRC components, indicating its role in supporting assembly and stability of the wider complex (PMID:36856967). In humans, loss-of-function variants produce a spectrum from primary ciliary dyskinesia-like ciliary beat abnormalities and dynein arm deficits to multiple morphological abnormalities of the sperm flagella (MMAF) with peripheral doublet dissociation, in some cases primarily affecting spermatogenesis without systemic PCD symptoms (PMID:23354437, PMID:36856967, PMID:39780445, PMID:35873463).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2013 High

    Established DRC1 as a structural N-DRC subunit essential for complex assembly and dynein regulation, defining its core molecular role across species.

    Evidence Loss-of-function mutations in Chlamydomonas and human patients, with axonemal EM and N-DRC assembly analysis

    PMID:23354437

    Open questions at the time
    • Did not resolve which other N-DRC subunits DRC1 directly contacts
    • No high-resolution structure of DRC1 within the complex
  2. 2021 High

    Distinguished tissue-specific consequences of DRC1 loss, showing flagella require DRC1 for overall axoneme structural stability whereas cilia do not, reframing DRC1 as more critical for flagellar integrity.

    Evidence Multiple Drc1 knockout and point-mutant knock-in mouse alleles with EM ultrastructure and motility analysis of cilia and sperm

    PMID:34169321

    Open questions at the time
    • Molecular basis for the differential flagellar versus ciliary vulnerability not defined
    • Does not establish DRC1 interaction partners directly
  3. 2022 Medium

    Confirmed in humans that DRC1 protein is required for normal regulatory complex assembly in both nasal cilia and sperm flagella, linking protein absence to reduced ciliary beat amplitude and sperm immotility.

    Evidence WES/CNV analysis with a homozygous exon deletion; immunofluorescence of DRC1 and other DRC proteins, high-speed video microscopy, sperm motility/morphology in a patient

    PMID:35873463

    Open questions at the time
    • Single patient limits generalization
    • Reciprocal partner validation not performed
  4. 2023 Medium

    Showed a nonsense variant reduces DRC1 mRNA and protein and perturbs expression of other N-DRC components, providing evidence that DRC1 supports stability of the wider complex and causes female infertility.

    Evidence WES, qPCR, immunofluorescence, TEM, and high-speed video microscopy in a single patient case

    PMID:36856967

    Open questions at the time
    • Single patient case
    • Interaction with other N-DRC elements inferred from expression, not direct binding assay
  5. 2025 Medium

    Demonstrated that complete DRC1 loss can produce MMAF with peripheral doublet dissociation in the absence of systemic PCD, indicating DRC1 deficiency can primarily manifest in spermatogenesis.

    Evidence WES, immunofluorescence of DRC1 in spermatozoa, and TEM of flagellar ultrastructure in four unrelated patients sharing a frameshift variant

    PMID:39780445

    Open questions at the time
    • Mechanism for sperm-restricted phenotype not established
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct binding partners of DRC1 within the N-DRC and the structural basis for its differential requirement in flagella versus cilia remain undefined.
  • No direct interaction map of DRC1 with specific N-DRC subunits
  • No structural model of DRC1 in the assembled complex
  • Molecular explanation for tissue-specific severity unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2
Localization
GO:0005929 cilium 4 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1474165 Reproduction 3
Complex memberships
axonemenexin-dynein regulatory complex (N-DRC)

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 DRC1 (CCDC164) encodes a subunit of the nexin-dynein regulatory complex (N-DRC) in the axoneme. Loss-of-function mutations in DRC1 cause severe defects in N-DRC assembly and result in defective ciliary movement, establishing DRC1 as essential for N-DRC structural integrity and dynein motor regulation in both Chlamydomonas and humans. Loss-of-function mutations in Chlamydomonas reinhardtii and human patients; electron microscopy of axonemal ultrastructure; analysis of N-DRC assembly Nature genetics High 23354437
2021 DRC1 is required for N-DRC assembly in both cilia and sperm flagella; absence of DRC1 leads to shortening of cilia and impaired motility, while flagellar damage is more severe, manifesting as complete axoneme structural disorder in addition to loss of the DRC structure. This demonstrates DRC1 is required for structural stability of flagella but not cilia. Drc1 knockout and point-mutant knock-in mice (Drc1-/-, Drc1R554X/R554X, Drc1W244X/W244X) on ICR background; electron microscopy of axoneme ultrastructure; motility analysis of cilia and sperm Human molecular genetics High 34169321
2023 A homozygous nonsense variant in DRC1 (p.Gln118Ter) results in decreased DRC1 mRNA and protein expression, dyskinetic ciliary beat with lower frequency, partial lack of dynein arms by TEM, and female infertility. Expression analysis suggested DRC1 may interact with other DRC complex elements, as loss of DRC1 affected expression of other N-DRC components. Whole-exome sequencing; qPCR for mRNA expression; immunofluorescence for protein localization; transmission electron microscopy of axoneme ultrastructure; high-speed video microscopy of ciliary motility Journal of assisted reproduction and genetics Medium 36856967
2025 A homozygous frameshift variant in DRC1 (c.109dup; p.Gln37ProfsTer30) causes complete absence of DRC1 protein in spermatozoa, with TEM showing peripheral doublet dissociation in ~10% of axonemal cross-sections, indicating N-DRC instability. This results in MMAF (multiple morphological abnormalities of sperm flagella) without systemic PCD symptoms, suggesting DRC1 deficiency can primarily affect spermatogenesis. Whole-exome sequencing; immunofluorescence to assess DRC1 protein expression in spermatozoa; transmission electron microscopy of flagellar ultrastructure Andrology Medium 39780445
2022 A novel homozygous DRC1 exon deletion (c.156-1724_244-2550del) causes absence of DRC1 protein in both nasal cilia and sperm flagella as shown by immunofluorescence, with reduced ciliary beating amplitude (but not frequency) and nearly immotile spermatozoa, confirming DRC1 protein is required for normal axonemal dynein regulatory complex assembly in both tissue types. WES-based CNV analysis; PCR and Sanger sequencing confirmation; immunofluorescence for DRC1 and other dynein regulatory complex proteins in cilia and sperm; high-speed video microscopy; sperm motility and morphology analysis Frontiers in genetics Medium 35873463

Source papers

Stage 0 corpus · 20 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans. Nature genetics 163 23354437
1999 DRC1, DNA replication and checkpoint protein 1, functions with DPB11 to control DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 101 10097122
2002 CDK phosphorylation of Drc1 regulates DNA replication in fission yeast. Current biology : CB 52 11937031
2021 Loss of DRC1 function leads to multiple morphological abnormalities of the sperm flagella and male infertility in human and mouse. Human molecular genetics 47 34169321
2019 Recurring large deletion in DRC1 (CCDC164) identified as causing primary ciliary dyskinesia in two Asian patients. Molecular genetics & genomic medicine 37 31270959
2020 Copy number variation in DRC1 is the major cause of primary ciliary dyskinesia in the Japanese population. Molecular genetics & genomic medicine 35 31960620
2011 CDK promotes interactions of Sld3 and Drc1 with Cut5 for initiation of DNA replication in fission yeast. Molecular biology of the cell 30 21593208
2019 Primary ciliary dyskinesia caused by a large homozygous deletion including exons 1-4 of DRC1 in Japanese patients with recurrent sinopulmonary infection. Molecular genetics & genomic medicine 26 31701675
2023 Prevalence and founder effect of DRC1 exon 1-4 deletion in Korean patients with primary ciliary dyskinesia. Journal of human genetics 12 36747106
2008 Identification of MSA1, a cell cycle-regulated, dosage suppressor of drc1/sld2 and dpb11 mutants. Cell cycle (Georgetown, Tex.) 9 18948746
1993 Stability analysis of the Lactococcus lactis DRC1 lactose plasmid using pulsed-field gel electrophoresis. Plasmid 7 8441771
2023 Characterization of a DRC1 null variant associated with primary ciliary dyskinesia and female infertility. Journal of assisted reproduction and genetics 6 36856967
2022 Case Report: Whole-Exome Sequencing-Based Copy Number Variation Analysis Identified a Novel DRC1 Homozygous Exon Deletion in a Patient With Primary Ciliary Dyskinesia. Frontiers in genetics 5 35873463
1988 Morphological diversity of DRC-1 positive cells: human follicular dendritic cells and their relatives. Advances in experimental medicine and biology 5 3254049
2025 A recurrent loss-of-function variant in DRC1 causes non-syndromic severe asthenozoospermia with favorable intracytoplasmic sperm injection and pregnancy outcomes. Andrology 4 39780445
2024 A 3000-year-old founder variant in the DRC1 gene causes primary ciliary dyskinesia in Japan and Korea. Journal of human genetics 1 39152285
2026 Clinical characteristics and severity of primary ciliary dyskinesia caused by large homozygous deletion including exons 1-4 of DRC1: A multicenter retrospective cohort study. Respiratory investigation 0 41570615
2026 First neonatal case of primary ciliary dyskinesia caused by a pathogenic DRC1 variant presenting with recurrent atelectasis and airway hypersecretion: a case report and literature review. BMC pediatrics 0 42185991
2024 A case of primary ciliary dyskinesis with DRC1 deletion and literature review: Additional evidence on the founder effect. Pediatrics international : official journal of the Japan Pediatric Society 0 39349394
2021 Expanded phenotype of primary ciliary dyskinesia related to DRC1 pathogenic variant with dysmorphisms and vascular anomalies. American journal of medical genetics. Part A 0 34851034

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