CCDC28B

UniProt ID: Q9BUN5
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

Coiled-coil domain-containing protein 28B (CCDC28B; historically MGC1203) is a small pericentriolar/basal-body-associated protein that acts as an accessory factor and genetic modifier of ciliary trafficking. It is required for normal ciliogenesis and for the control of cilium length, and it physically interacts with multiple Bardet-Biedl syndrome (BBSome) subunits, including BBS1, BBS2, BBS4, BBS5, BBS6, BBS7 and TTC8/BBS8, with which it colocalizes near centrosomes and basal bodies. Functionally, CCDC28B regulates cilium length in part through its interaction with SIN1/MAPKAP1 and acts as a positive regulator of mTOR complex 2 (mTORC2) assembly and activity; its effect on cilium length appears to be largely independent of canonical mTOR signaling. Depletion of the protein causes defective ciliogenesis in cultured cells and ciliopathy-like phenotypes in zebrafish (hydrocephalus, left-right axis defects, renal dysfunction). It is not a numbered structural BBS subunit but a modifier of BBSome-dependent ciliary function; homologous sequences are restricted to ciliated metazoa.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005813 centrosome
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetically inferred centrosome localization. Consistent with the experimentally observed pericentriolar/basal-body localization of CCDC28B and with the localization of BBSome-associated proteins.
Reason: Localization is supported by direct experimental evidence (PMID:16327777) and is biologically coherent; however it is a subcellular-location annotation rather than the protein's core function (ciliogenesis/cilium-length control).
GO:0005813 centrosome
IEA
GO_REF:0000044 		ACCEPT
Summary: Electronic annotation derived from UniProt subcellular-location vocabulary mapping. Redundant with the experimental IDA centrosome annotation from PMID:16327777.
Reason: The localization is correct and corroborated experimentally, though this electronic entry is redundant with the IDA evidence and is a non-core localization annotation.
GO:0005515 protein binding
IPI
PMID:16327777
Dissection of epistasis in oligogenic Bardet-Biedl syndrome. 		MARK AS OVER ANNOTATED
Summary: IPI annotation capturing physical interactions with BBSome subunits (WITH includes BBS4/Q96RK4 and other BBS proteins). The underlying interactions are real and central to CCDC28B biology, but "protein binding" is an uninformative molecular-function term that conveys no specific activity.
Reason: Per curation guidelines, the bare "protein binding" term should be avoided. The biologically meaningful content (binding to BBSome subunits near the basal body) is better represented by the ciliogenesis process annotation and by localization terms rather than by an uninformative MF term.
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network. 		MARK AS OVER ANNOTATED
Summary: IPI annotation from a proteome-scale binary (Y2H) interactome map, supporting a CCDC28B-ATRIP (Q8WXE1) interaction. This is a single high-throughput binary hit and the term itself is uninformative.
Reason: "Protein binding" is discouraged as uninformative, and this is a single high-throughput interactome data point whose biological relevance to CCDC28B function is unestablished.
GO:0005813 centrosome
IDA
PMID:16327777
Dissection of epistasis in oligogenic Bardet-Biedl syndrome. 		ACCEPT
Summary: Direct experimental evidence that CCDC28B is a pericentriolar protein localizing near centrosomes and basal bodies, where it colocalizes with BBS proteins. The falcon deep-research synthesis is consistent with this, describing CCDC28B as concentrating at the ciliary basal body (the microtubule-organizing center from which the primary cilium extends).
Reason: Well-supported direct localization evidence. This is a core localization for CCDC28B, consistent with its role at the base of the cilium.
Supporting Evidence:
file:human/CCDC28B/CCDC28B-deep-research-falcon.md
CCDC28B concentrates at the basal body, the microtubule organizing center from which the primary cilium extends
GO:0060271 cilium assembly
IMP
PMID:23015189
Characterization of CCDC28B reveals its role in ciliogenesis... 		ACCEPT
Summary: Loss-of-function (IMP) evidence that CCDC28B is required for ciliogenesis, shown both in cultured cells and in zebrafish, where depletion produces ciliopathy phenotypes (hydrocephalus, left-right axis defects, renal impairment). This is the best-supported functional annotation and reflects the gene's core biological role. Subsequent literature, as synthesized in the falcon deep-research report, reinforces that CCDC28B acts as a positive regulator of ciliogenesis and cilium length rather than a passive structural component.
Reason: Strong experimental loss-of-function evidence across cell and animal models; represents the core function of CCDC28B as a ciliogenesis factor.
Supporting Evidence:
PMID:23015189
show it affects ciliogenesis both in cultured cells and in vivo in zebrafish
file:human/CCDC28B/CCDC28B-deep-research-falcon.md
CCDC28B positively regulates primary cilium length and promotes ciliogenesis in somatic cells

Core Functions

Required for ciliogenesis; CCDC28B acts as an accessory factor at the base of the cilium that supports normal cilium assembly and the regulation of cilium length.

Supporting Evidence:
  • PMID:23015189
    show it affects ciliogenesis both in cultured cells and in vivo in zebrafish ... Depletion of Ccdc28b in zebrafish results in defective ciliogenesis
  • PMID:23727834
    Ccdc28b regulates cilia length in vivo, at least in part, through its interaction with Sin1

Physically associates with BBSome subunits (BBS1, BBS2, BBS4, BBS5, BBS6, BBS7, TTC8/BBS8) near centrosomes and basal bodies, functioning as a modifier/accessory factor of BBSome-dependent ciliary trafficking rather than as a structural BBSome subunit.

Supporting Evidence:
  • PMID:16327777
    MGC1203 encodes a pericentriolar protein that interacts and colocalizes with the BBS proteins
  • file:human/CCDC28B/CCDC28B-deep-research-falcon.md
    While CCDC28B is not a core BBSome subunit, it functions as a BBS-associated modifier protein that supports BBSome-mediated ciliary homeostasis

Positively regulates mTOR complex 2 (mTORC2) assembly and activity through interaction with SIN1/MAPKAP1, with the cilium-length-control function being largely independent of canonical mTOR signaling.

Supporting Evidence:
  • PMID:23727834
    CCDC28B is a positive regulator of mTORC2, participating in its assembly/stability and modulating its activity, while not affecting mTORC1 function

References

GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
PMID:16327777
Dissection of epistasis in oligogenic Bardet-Biedl syndrome.
PMID:23015189
Characterization of CCDC28B reveals its role in ciliogenesis and provides insight to understand its modifier effect on Bardet-Biedl syndrome.
PMID:23727834
The Bardet-Biedl syndrome-related protein CCDC28B modulates mTORC2 function and interacts with SIN1 to control cilia length independently of the mTOR complex.
PMID:25416956
A proteome-scale map of the human interactome network.
file:human/CCDC28B/CCDC28B-deep-research-falcon.md
Falcon deep research report for CCDC28B

Suggested Questions for Experts

Q: Is CCDC28B a stable, stoichiometric component of the BBSome (GO:0034464), or a transient/peripheral interactor that modulates BBSome function without being part of the core complex?

Q: Does CCDC28B localize within the cilium proper (e.g., transition zone or axoneme) or is it restricted to the pericentriolar/basal-body region?

Q: What is the molecular activity by which CCDC28B controls cilium length, whether primarily through SIN1 scaffolding, through IFT/BBSome trafficking, or both?

Suggested Experiments

Experiment: Determine whether CCDC28B co-fractionates stoichiometrically with the BBSome by size-exclusion chromatography and quantitative mass spectrometry, to test BBSome membership versus accessory association.

Experiment: Use proximity labeling (BioID/TurboID) from CCDC28B in ciliated cells to define its in vivo interaction neighborhood at the basal body, transition zone, and cilium.

Experiment: Perform live-imaging of cilium assembly and length dynamics in CCDC28B-null cells with rescue by separation-of-function mutants (SIN1-binding versus BBSome-binding deficient) to dissect the mechanism of cilium-length control.

Deep Research

Falcon

(CCDC28B-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 24 citations 1 artifacts 2026-06-20T06:14:52.112353
Edison artifact artifact-00 (text/markdown)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive Research Report: CCDC28B (Coiled-Coil Domain-Containing Protein 28B)

Gene and Protein Identity

CCDC28B (UniProt: Q9BUN5) encodes Coiled-coil domain-containing protein 28B in humans (Homo sapiens). The protein contains a CCDC28 domain (IPR025271; PF13270), which is characteristic of this protein family (florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6). CCDC28B is an evolutionarily conserved gene with a paralog, CCDC28A, which shows distinct tissue-specific expression patterns—CCDC28A is expressed in male germ cells, while CCDC28B is expressed in somatic supporting cells in mice (stojanovic2024ccdc28adeficiencycauses pages 1-3). This distinction suggests functional divergence following gene duplication.

Primary Function and Molecular Role

CCDC28B functions as a non-enzymatic regulatory protein that plays a critical role in ciliogenesis and ciliary homeostasis. The protein is not a catalyst but rather acts as a structural adaptor or regulatory factor within ciliary biology (linnert2025thebbscctchaperonin pages 3-7, florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6). Specifically, CCDC28B positively regulates primary cilium length and promotes ciliogenesis in somatic cells (stojanovic2024ccdc28adeficiencycauses pages 1-3, linnert2025thebbscctchaperonin pages 3-7).

Recent studies have demonstrated that CCDC28B depletion or loss causes impaired ciliogenesis in both mammalian cell lines and zebrafish models. In zebrafish, ccdc28b morphants exhibit perturbed pronephron ciliogenesis, highlighting the conserved developmental importance of this protein across vertebrates (adamiokostrowska2020ciliarygenesin pages 3-6). These experimental findings establish CCDC28B as an essential positive regulator of ciliary assembly and maintenance rather than a passive structural component.

Subcellular Localization

CCDC28B exhibits dynamic subcellular localization patterns. The protein primarily localizes to ciliary compartments, specifically:

  1. Ciliary basal body: CCDC28B concentrates at the basal body, the microtubule organizing center from which the primary cilium extends (florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6, chen2021dynamicchangesof pages 9-11).

  2. Ciliary axoneme: The protein is also found along the ciliary axoneme, the microtubule-based core structure of the cilium (florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6).

  3. Nucleus: Intriguingly, when the kinesin motor protein KIF5B is targeted or inhibited, CCDC28B accumulates in the nucleus (li2024regulationofciliary pages 5-6). This observation suggests that CCDC28B may have dual localization capabilities and potential nuclear functions beyond its well-established ciliary roles (ewerling2023neofunctionalizationofciliary pages 2-5).

The localization of CCDC28B is dynamically regulated by KIF5B, a kinesin-1 subunit that functions in intracellular transport (li2024regulationofciliary pages 5-6, marom2023dominantnegativevariants pages 19-20). This interaction underscores the importance of microtubule-based transport in positioning ciliary regulatory proteins.

Protein-Protein Interactions and Molecular Mechanisms

CCDC28B functions within a broader network of BBS (Bardet-Biedl syndrome) proteins and ciliary assembly factors. Key interaction partners and functional associations include:

  1. BBS proteins and the BBSome complex: CCDC28B is functionally associated with BBS proteins and the BBSome, an octameric protein complex that regulates ciliary trafficking and signaling (linnert2025thebbscctchaperonin pages 3-7, ewerling2023neofunctionalizationofciliary pages 2-5, novas2015bardet–biedlsyndromeis pages 4-5). While CCDC28B is not a core BBSome subunit, it functions as a BBS-associated modifier protein that supports BBSome-mediated ciliary homeostasis.

  2. BBS/CCT chaperonin machinery: CCDC28B interacts with or is regulated by the BBS/CCT (TRiC) chaperonin complex, which facilitates the proper folding and assembly of BBSome components (linnert2025thebbscctchaperonin pages 3-7). This connection places CCDC28B within the broader proteostasis network required for ciliary protein quality control.

  3. KIF5B kinesin motor protein: As mentioned, KIF5B directly regulates CCDC28B localization, and disruption of this interaction leads to nuclear accumulation of CCDC28B (li2024regulationofciliary pages 5-6, marom2023dominantnegativevariants pages 19-20). This suggests that active transport mechanisms are essential for maintaining proper CCDC28B distribution within the cell.

The coiled-coil domain structure of CCDC28B likely mediates many of these protein-protein interactions, as coiled-coil motifs are well-known structural elements that facilitate protein complex assembly.

Biological Processes and Signaling Pathways

CCDC28B participates in multiple biological processes and signaling pathways:

1. Ciliogenesis and Ciliary Maintenance

The most well-established function of CCDC28B is its role in promoting primary cilium assembly and regulating ciliary length (stojanovic2024ccdc28adeficiencycauses pages 1-3, linnert2025thebbscctchaperonin pages 3-7). Primary cilia are sensory organelles that extend from the cell surface and are essential for transducing developmental and homeostatic signals.

2. BBSome-Mediated Ciliary Trafficking

Through its association with the BBSome, CCDC28B contributes to the intraflagellar transport (IFT) and trafficking of proteins into and out of the cilium (linnert2025thebbscctchaperonin pages 3-7, novas2015bardet–biedlsyndromeis pages 4-5). The BBSome acts as a cargo adapter that recognizes ciliary membrane proteins and facilitates their removal from cilia, and CCDC28B appears to support this process.

3. Hedgehog Signaling Pathway

Since primary cilia are essential for Hedgehog (Hh) signal transduction in vertebrates, and CCDC28B is required for proper ciliary structure, the protein indirectly influences Hedgehog signaling (novas2015bardet–biedlsyndromeis pages 4-5). Disruption of ciliary structure due to CCDC28B deficiency would be expected to impair Hedgehog pathway activation.

4. Immune Regulation

Interestingly, single-cell RNA sequencing studies have identified CCDC28B as one of several genes significantly upregulated in regulatory B cells (Breg cells) across multiple organs including liver, spleen, bone marrow, and peritoneal cavity (yang2021characterizationoforganspecific pages 3-6). In this context, CCDC28B was identified alongside other Breg markers such as Fcrl5, Zbtb20, Cd9, and Ptpn22. Non-B10 Breg cells expressing CCDC28B showed enrichment in TGF-β pathway activation, suggesting a role in immunosuppressive functions (yang2021characterizationoforganspecific pages 3-6). The mechanistic connection between CCDC28B's ciliary functions and its expression in immune cells remains to be fully elucidated, but primary cilia are known to be present on immune cells and may contribute to immune cell signaling.

5. Neurodevelopment and Brain Aging

Analysis of human brain transcriptomes across the lifespan revealed that CCDC28B is one of the ciliary genes showing age-dependent expression patterns in multiple brain regions (chen2021dynamicchangesof pages 9-11). This dynamic regulation suggests that CCDC28B plays a role in brain cilia physiology throughout development and aging, potentially contributing to neurodevelopmental processes and age-related neurological changes.

6. Association with Hypertension and Aging Phenotypes

Genetic studies in OXYS rats, a model of accelerated senescence, identified single-nucleotide polymorphisms (SNPs) in Ccdc28b as candidate variants associated with both hypertension and accelerated aging traits (devyatkin2020singlenucleotidepolymorphisms(snps) pages 12-14). While these associations require further validation, they suggest that CCDC28B may have pleiotropic effects beyond classic ciliopathy phenotypes. Additionally, selective sweep analysis in wild mouse populations identified the Ccdc28b locus as a target of positive selection, indicating adaptive evolution at this gene (lawal2021selectionshapesthe pages 7-10).

Disease Associations: Bardet-Biedl Syndrome and Ciliopathies

CCDC28B is classified as a BBS-associated or modifier gene in the context of Bardet-Biedl syndrome (BBS), a multisystem ciliopathy (stojanovic2024ccdc28adeficiencycauses pages 1-3, lawal2021selectionshapesthe pages 7-10, florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6). BBS is characterized by retinal degeneration, obesity, polydactyly, intellectual disability, renal abnormalities, and other features stemming from ciliary dysfunction.

Mutations in CCDC28B have been linked to ciliopathy phenotypes, and the gene is included in ciliopathy gene panels for diagnostic purposes (benitez2026aglobalsurvey pages 5-9). A study noted that CCDC28B variants, including a heterozygous c.430C>T variant that introduces a premature termination codon, can contribute to BBS pathology by reducing CCDC28B protein levels (florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6). The protein's role as a modifier suggests that while CCDC28B mutations alone may not cause BBS, they can exacerbate disease severity or contribute to phenotypic variability when combined with mutations in core BBS genes.

Experimental evidence from model organisms supports the ciliopathy association. Zebrafish ccdc28b morphants display perturbed pronephron ciliogenesis, a phenotype consistent with ciliopathy models (adamiokostrowska2020ciliarygenesin pages 3-6). In mice, deletion of the BBS modifier gene Ccdc28b has been shown to impact ciliary phenotypes and developmental processes (migliavacca2015apotentialcontributory pages 3-4).

Structural and Evolutionary Insights

CCDC28B contains characteristic coiled-coil domains (CCDC28 family domain, IPR025271; PF13270), which are α-helical structural motifs that facilitate protein-protein interactions. The coiled-coil architecture likely enables CCDC28B to bind to BBS proteins, chaperonins, and other ciliary factors, thereby coordinating multi-protein complexes essential for ciliary function.

Evolutionarily, CCDC28B is conserved across vertebrates, indicating that its ciliary functions have been maintained throughout vertebrate evolution. The existence of the paralog CCDC28A with distinct expression patterns (germ cell-specific vs. somatic) suggests functional specialization following gene duplication (stojanovic2024ccdc28adeficiencycauses pages 1-3). The conservation of ciliary function in zebrafish further demonstrates that the core role of CCDC28B in ciliogenesis is ancient and fundamental to vertebrate biology.

Current Understanding and Research Gaps

While significant progress has been made in understanding CCDC28B's role in ciliogenesis and its association with BBS, several questions remain:

  1. Molecular mechanisms: The precise molecular interactions between CCDC28B and BBSome components need further characterization. High-resolution structural studies of CCDC28B in complex with its binding partners would provide insights into its mechanism of action.

  2. Nuclear functions: The observation that CCDC28B can accumulate in the nucleus when KIF5B is disrupted raises the possibility of nuclear roles beyond ciliary regulation (li2024regulationofciliary pages 5-6, ewerling2023neofunctionalizationofciliary pages 2-5). Recent studies have shown that several ciliary proteins have dual functions in the nucleus, particularly in gene expression regulation and DNA damage response. Whether CCDC28B has analogous nuclear functions remains to be determined.

  3. Immune cell function: The upregulation of CCDC28B in regulatory B cells and its association with immunosuppressive pathways is intriguing but mechanistically unexplored (yang2021characterizationoforganspecific pages 3-6). Understanding whether primary cilia on B cells contribute to CCDC28B's immune functions could reveal novel connections between ciliary biology and immunity.

  4. Therapeutic targeting: Given CCDC28B's role as a BBS modifier, strategies to enhance CCDC28B function or compensate for its loss could have therapeutic potential in ciliopathies. However, no therapies targeting CCDC28B are currently available.

Summary

Aspect of CCDC28B biology Protein / gene Primary cellular function Subcellular localization Key interactions / binding partners Associated pathways / processes Disease / phenotype associations Key supporting citations
Core identity Coiled-coil domain-containing protein 28B (CCDC28B); human UniProt Q9BUN5 Non-enzymatic coiled-coil protein; current literature supports a regulatory/adaptor-like role rather than catalytic activity Primarily linked to ciliary compartments Broad association with BBS-related protein networks Ciliogenesis; ciliary homeostasis Considered a BBS-associated/modifier gene in ciliopathy literature 2021 review/localization table (florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6); 2023 BBSome review context (ewerling2023neofunctionalizationofciliary pages 2-5)
Positive regulator of ciliogenesis / cilium length CCDC28B Promotes ciliogenesis and positively regulates cilia length in somatic cells Primary cilium, especially basal body/ciliary region Functionally associated with BBS proteins and ciliary machinery Primary cilium assembly and maintenance Loss or depletion causes impaired ciliogenesis in mammalian cells and zebrafish; relevant to ciliopathies 2024 CCDC28A paper summarizing prior CCDC28B evidence (stojanovic2024ccdc28adeficiencycauses pages 1-3); 2025 ADGRV1/BBS-CCT paper citing positive regulation of cilia length (linnert2025thebbscctchaperonin pages 3-7)
BBS-associated modifier role CCDC28B Acts as a modifier/regulatory factor rather than a core BBSome subunit Basal body / cilium-associated compartments Associated with BBS proteins and BBSome-related networks BBS-related ciliary biology Variants/mutations associated with Bardet-Biedl syndrome; modifier effects discussed in BBS literature 2021 BBS genotype-phenotype review (florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6); 2024 CCDC28A paper background (stojanovic2024ccdc28adeficiencycauses pages 1-3); 2021 mouse selection paper summarizing BBS link (lawal2021selectionshapesthe pages 7-10)
Subcellular localization in ciliary structures CCDC28B Executes ciliary regulatory functions where cilia are assembled and maintained Basal body and ciliary axoneme/cilium; low tissue specificity in review table Likely engages local ciliary assembly and transport proteins Ciliogenesis; ciliary trafficking Mislocalization or loss expected to perturb ciliary structure/function 2021 localization table listing basal body/cilium localization (florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6); 2021 brain cilia transcriptome review snippet noting localization (chen2021dynamicchangesof pages 9-11)
KIF5B-regulated localization and possible nuclear shuttling CCDC28B Localization is dynamically regulated; KIF5B targeting causes nuclear accumulation of CCDC28B, suggesting extra-ciliary/nuclear potential Cilium/basal body and nucleus under altered transport conditions KIF5B Ciliary homeostasis; possible nucleocytoplasmic trafficking-linked regulation May connect ciliary defects to broader cell biological phenotypes 2024 review on non-IFT kinesins stating KIF5B targeting leads to nuclear accumulation (li2024regulationofciliary pages 5-6); 2023 KIF5B disease paper referencing direct interaction at ciliary basal body (marom2023dominantnegativevariants pages 19-20); 2023 evolutionary/nuclear roles review mentioning predicted/possible nuclear roles (ewerling2023neofunctionalizationofciliary pages 2-5)
Relationship to BBSome / BBS-CCT chaperonin biology CCDC28B Functions in the broader BBS protein network that supports ciliary protein localization and homeostasis Ciliary base / basal body-associated region BBS proteins; BBS/CCT chaperonin-related machinery BBSome-mediated trafficking; ciliary proteostasis Dysfunction likely contributes to BBS-related cellular phenotypes 2025 ADGRV1/BBS-CCT paper discussing CCDC28B as BBS-associated protein (linnert2025thebbscctchaperonin pages 3-7); 2015 BBS review summarizing BBS protein trafficking functions (novas2015bardet–biedlsyndromeis pages 4-5); 2023 BBSome review context (ewerling2023neofunctionalizationofciliary pages 2-5)
Developmental and organ-specific ciliary roles CCDC28B Conserved ciliary regulator in vertebrate development Somatic-cell cilia, including pronephric/renal cilia in zebrafish models Ciliary assembly factors (functional association rather than direct binding established here) Pronephron ciliogenesis; developmental cilia function Perturbed pronephron ciliogenesis in zebrafish morphants; supports conserved developmental role 2020 renal ciliopathy review summarizing zebrafish pronephron phenotype (adamiokostrowska2020ciliarygenesin pages 3-6); 2024 CCDC28A paper background noting zebrafish and mammalian ciliogenesis defects (stojanovic2024ccdc28adeficiencycauses pages 1-3)
Brain / lifespan expression dynamics CCDC28B Cilia-related transcript with age-dependent regulation in human brain regions Inferred to function in neuronal primary cilia-related compartments Not specifically defined in this dataset Brain cilia biology; neurodevelopment/aging-linked ciliary regulation Suggests possible relevance to age-dependent brain cilia physiology and neurological phenotypes seen in ciliopathies 2021 human brain cilia transcriptome study identifying CCDC28B as age-regulated cilia transcript (chen2021dynamicchangesof pages 9-11)
Immune-cell expression signature CCDC28B Upregulated marker-like transcript in regulatory B cells; exact mechanistic role remains unclear Identified by scRNA-seq in Breg populations across organs Co-expressed with Cd9, Ptpn22, Fcrl5, Zbtb20 in Bregs Immunoregulatory programs; Breg-associated signatures; non-B10 Bregs linked to TGF-β pathways No direct causal disease role established here, but suggests broader biology beyond classic ciliogenesis 2021 single-cell Breg study (yang2021characterizationoforganspecific pages 3-6)
Genetic / disease-association evidence beyond classic ciliopathy CCDC28B Candidate modifier or susceptibility gene based on genetic association studies Not localization-focused Not specified Hypertension/aging-associated genetics in rat; adaptive selection signals in mouse populations Candidate SNPs linked to hypertension and accelerated-senescence traits in OXYS rats; selective sweep overlaps in wild mice; relevance remains inferential for human disease 2020 rat SNP study (devyatkin2020singlenucleotidepolymorphisms(snps) pages 12-14); 2021 wild mouse selection study (lawal2021selectionshapesthe pages 7-10)

Table: This table summarizes the major experimentally supported and review-supported functional properties of human CCDC28B, emphasizing its role in ciliogenesis, localization, interaction networks, pathways, and disease relevance. It is useful as a compact evidence map linking CCDC28B biology to Bardet-Biedl syndrome and broader ciliary processes.

In summary, CCDC28B (UniProt: Q9BUN5) is a coiled-coil domain-containing protein that functions as a positive regulator of ciliogenesis and ciliary homeostasis. The protein localizes primarily to the ciliary basal body and axoneme, where it interacts with BBS proteins, the BBSome complex, and the BBS/CCT chaperonin machinery to support ciliary assembly and maintenance (stojanovic2024ccdc28adeficiencycauses pages 1-3, linnert2025thebbscctchaperonin pages 3-7, florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6). CCDC28B is not an enzyme but rather a structural adaptor or regulatory factor whose localization is dynamically controlled by the KIF5B kinesin motor protein (li2024regulationofciliary pages 5-6, marom2023dominantnegativevariants pages 19-20).

The protein plays critical roles in multiple biological processes including BBSome-mediated ciliary trafficking, Hedgehog signaling (indirectly through cilia), immune regulation in B cells, and neurodevelopment (chen2021dynamicchangesof pages 9-11, yang2021characterizationoforganspecific pages 3-6, novas2015bardet–biedlsyndromeis pages 4-5). CCDC28B is associated with Bardet-Biedl syndrome as a modifier gene, and loss-of-function studies in zebrafish and mammalian cells confirm its essential role in ciliogenesis (adamiokostrowska2020ciliarygenesin pages 3-6, florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6, benitez2026aglobalsurvey pages 5-9). Recent evidence also suggests potential nuclear functions and connections to age-related phenotypes including hypertension and senescence (chen2021dynamicchangesof pages 9-11, ewerling2023neofunctionalizationofciliary pages 2-5, devyatkin2020singlenucleotidepolymorphisms(snps) pages 12-14).

From a structural perspective, CCDC28B's coiled-coil domains enable protein-protein interactions that are central to its function, and the gene is evolutionarily conserved across vertebrates with a paralog (CCDC28A) showing tissue-specific divergence (stojanovic2024ccdc28adeficiencycauses pages 1-3). Future research should focus on elucidating the molecular details of CCDC28B's interactions with BBSome components, investigating its potential nuclear roles, and exploring its unexpected involvement in immune regulation. These efforts may reveal new therapeutic strategies for ciliopathies and other CCDC28B-associated conditions.

References

  1. (florea2021bardet–biedlsyndrome—multiplekaleidoscope pages 5-6): Laura Florea, Lavinia Caba, and Eusebiu Vlad Gorduza. Bardet–biedl syndrome—multiple kaleidoscope images: insight into mechanisms of genotype–phenotype correlations. Genes, 12:1353, Aug 2021. URL: https://doi.org/10.3390/genes12091353, doi:10.3390/genes12091353. This article has 64 citations.

  2. (stojanovic2024ccdc28adeficiencycauses pages 1-3): Nena Stojanovic, Rosario Ortiz Hernández, Nayeli Torres Ramírez, Olga Margarita Echeverría Martínez, Abrahan Hernández Hernández, and Hiroki Shibuya. Ccdc28a deficiency causes head-tail coupling defects and immotility in murine spermatozoa. Scientific Reports, Nov 2024. URL: https://doi.org/10.1038/s41598-024-78453-9, doi:10.1038/s41598-024-78453-9. This article has 3 citations and is from a peer-reviewed journal.

  3. (linnert2025thebbscctchaperonin pages 3-7): Joshua Linnert, Deva Krupakar Kusuluri, Baran E. Güler, Sarita Rani Patnaik, Helen Louise May-Simera, and Uwe Wolfrum. The bbs/cct chaperonin complex ensures the localization of the adhesion g protein-coupled receptor adgrv1 to the base of primary cilia. Mar 2025. URL: https://doi.org/10.3389/fcell.2025.1520723, doi:10.3389/fcell.2025.1520723. This article has 3 citations.

  4. (adamiokostrowska2020ciliarygenesin pages 3-6): Anna Adamiok-Ostrowska and Agnieszka Piekiełko-Witkowska. Ciliary genes in renal cystic diseases. Cells, 9:907, Apr 2020. URL: https://doi.org/10.3390/cells9040907, doi:10.3390/cells9040907. This article has 53 citations.

  5. (chen2021dynamicchangesof pages 9-11): Siwei Chen, Wedad Alhassen, Roudabeh Vakil Monfared, Benjamin Vachirakorntong, Surya M. Nauli, Pierre Baldi, and Amal Alachkar. Dynamic changes of brain cilia transcriptomes across the human lifespan. International Journal of Molecular Sciences, 22:10387, Sep 2021. URL: https://doi.org/10.3390/ijms221910387, doi:10.3390/ijms221910387. This article has 22 citations.

  6. (li2024regulationofciliary pages 5-6): Lin Li and Jie Ran. Regulation of ciliary homeostasis by intraflagellar transport-independent kinesins. Cell Death & Disease, Jan 2024. URL: https://doi.org/10.1038/s41419-024-06428-9, doi:10.1038/s41419-024-06428-9. This article has 20 citations and is from a peer-reviewed journal.

  7. (ewerling2023neofunctionalizationofciliary pages 2-5): Alexander Ewerling, Vanessa Maissl, Bill Wickstead, and Helen Louise May-Simera. Neofunctionalization of ciliary bbs proteins to nuclear roles is likely a frequent innovation across eukaryotes. iScience, Mar 2023. URL: https://doi.org/10.1016/j.isci.2023.106410, doi:10.1016/j.isci.2023.106410. This article has 13 citations and is from a peer-reviewed journal.

  8. (marom2023dominantnegativevariants pages 19-20): Ronit Marom, Bo Zhang, Megan E. Washington, I-Wen Song, Lindsay C. Burrage, Vittoria C. Rossi, Ava S. Berrier, Anika Lindsey, Jacob Lesinski, Michael L. Nonet, Jian Chen, Dustin Baldridge, Gary A. Silverman, V. Reid Sutton, Jill A. Rosenfeld, Alyssa A. Tran, M. John Hicks, David R. Murdock, Hongzheng Dai, MaryAnn Weis, Shalini N. Jhangiani, Donna M. Muzny, Richard A. Gibbs, Richard Caswell, Carrie Pottinger, Deirdre Cilliers, Karen Stals, David Eyre, Deborah Krakow, Tim Schedl, Stephen C. Pak, and Brendan H. Lee. Dominant negative variants in kif5b cause osteogenesis imperfecta via down regulation of mtor signaling. PLOS Genetics, 19:e1011005, Nov 2023. URL: https://doi.org/10.1371/journal.pgen.1011005, doi:10.1371/journal.pgen.1011005. This article has 18 citations and is from a domain leading peer-reviewed journal.

  9. (novas2015bardet–biedlsyndromeis pages 4-5): Rossina Novas, Magdalena Cardenas-Rodriguez, Florencia Irigoín, and Jose L. Badano. Bardet–biedl syndrome: is it only cilia dysfunction? FEBS Letters, 589:3479-3491, Nov 2015. URL: https://doi.org/10.1016/j.febslet.2015.07.031, doi:10.1016/j.febslet.2015.07.031. This article has 111 citations and is from a peer-reviewed journal.

  10. (yang2021characterizationoforganspecific pages 3-6): Si-Yu Yang, Jie Long, Meng-Xing Huang, Pan-Yue Luo, Zhen-Hua Bian, Ya-Fei Xu, Cheng-Bo Wang, Shu-Han Yang, Liang Li, Carlo Selmi, M. Eric Gershwin, Zhi-Bin Zhao, and Zhe-Xiong Lian. Characterization of organ-specific regulatory b cells using single-cell rna sequencing. Frontiers in Immunology, Sep 2021. URL: https://doi.org/10.3389/fimmu.2021.711980, doi:10.3389/fimmu.2021.711980. This article has 49 citations and is from a peer-reviewed journal.

  11. (devyatkin2020singlenucleotidepolymorphisms(snps) pages 12-14): Vasiliy A. Devyatkin, Olga E. Redina, Natalia A. Muraleva, and Nataliya G. Kolosova. Single-nucleotide polymorphisms (snps) both associated with hypertension and contributing to accelerated-senescence traits in oxys rats. International Journal of Molecular Sciences, 21:3542, May 2020. URL: https://doi.org/10.3390/ijms21103542, doi:10.3390/ijms21103542. This article has 6 citations.

  12. (lawal2021selectionshapesthe pages 7-10): Raman Akinyanju Lawal, Uma P. Arora, and Beth L. Dumont. Selection shapes the landscape of functional variation in wild house mice. BMC Biology, Nov 2021. URL: https://doi.org/10.1186/s12915-021-01165-3, doi:10.1186/s12915-021-01165-3. This article has 18 citations and is from a domain leading peer-reviewed journal.

  13. (benitez2026aglobalsurvey pages 5-9): Yolanda Benítez, Graciela Uría-Regojo, and Pablo Mínguez. A global survey of systems biology-based predictions of gene-rare disease associations to enhance new diagnoses. Scientific Reports, May 2026. URL: https://doi.org/10.1038/s41598-026-54510-3, doi:10.1038/s41598-026-54510-3. This article has 0 citations and is from a peer-reviewed journal.

  14. (migliavacca2015apotentialcontributory pages 3-4): Eugenia Migliavacca, Christelle Golzio, Katrin Männik, Ian Blumenthal, Edwin C. Oh, Louise Harewood, Jack A. Kosmicki, Maria Nicla Loviglio, Giuliana Giannuzzi, Loyse Hippolyte, Anne M. Maillard, Ali Abdullah Alfaiz, Mieke M. van Haelst, Joris Andrieux, James F. Gusella, Mark J. Daly, Jacques S. Beckmann, Sébastien Jacquemont, Michael E. Talkowski, Nicholas Katsanis, Alexandre Reymond, Eugenia Migliavacca, Katrin Männik, Louise Harewood, Maria Nicla Loviglio, Robert Witwicki, Gérard Didelot, Ilse van der Werf, Ali A. Alfaiz, Marianna Zazhytska, Giuliana Giannuzzi, Jacqueline Chrast, Aurélien Macé, Sven Bergmann, Zoltan Kutalik, Loyse Hippolyte, Anne M. Maillard, Vanessa Siffredi, Flore Zufferey, Danielle Martinet, Frédérique Bena, Anita Rauch, Sonia Bouquillon, Joris Andrieux, Bruno Delobel, Odile Boute, Bénédicte Duban-Bedu, Cédric Le Caignec, Bertrand Isidor, Jean Chiesa, Boris Keren, Brigitte Gilbert-Dussardier, Renaud Touraine, Dominique Campion, Caroline Rooryck Thambo, Michèle Mathieu-Dramard, Ghislaine Plessis, Frank Kooy, Hilde Peeters, Katrin Ounap, Anneke T. Vulto-van Silfhout, Bert B. de Vries, Ellen van Binsbergen, Mieke M. van Haelst, Ann Nordgren, Mafalda Mucciolo, Alessandra Renieri, Evica Rajcan-Separovic, John A. Philipps, Richard J. Ellis, Jacques S. Beckmann, Sébastien Jacquemont, and Alexandre Reymond. A potential contributory role for ciliary dysfunction in the 16p11.2 600 kb bp4-bp5 pathology. The American Journal of Human Genetics, 96:784-796, May 2015. URL: https://doi.org/10.1016/j.ajhg.2015.04.002, doi:10.1016/j.ajhg.2015.04.002. This article has 74 citations.

Artifacts

Citations

  1. adamiokostrowska2020ciliarygenesin pages 3-6
  2. li2024regulationofciliary pages 5-6
  3. ewerling2023neofunctionalizationofciliary pages 2-5
  4. linnert2025thebbscctchaperonin pages 3-7
  5. yang2021characterizationoforganspecific pages 3-6
  6. chen2021dynamicchangesof pages 9-11
  7. lawal2021selectionshapesthe pages 7-10
  8. benitez2026aglobalsurvey pages 5-9
  9. migliavacca2015apotentialcontributory pages 3-4
  10. marom2023dominantnegativevariants pages 19-20
  11. https://doi.org/10.3390/genes12091353,
  12. https://doi.org/10.1038/s41598-024-78453-9,
  13. https://doi.org/10.3389/fcell.2025.1520723,
  14. https://doi.org/10.3390/cells9040907,
  15. https://doi.org/10.3390/ijms221910387,
  16. https://doi.org/10.1038/s41419-024-06428-9,
  17. https://doi.org/10.1016/j.isci.2023.106410,
  18. https://doi.org/10.1371/journal.pgen.1011005,
  19. https://doi.org/10.1016/j.febslet.2015.07.031,
  20. https://doi.org/10.3389/fimmu.2021.711980,
  21. https://doi.org/10.3390/ijms21103542,
  22. https://doi.org/10.1186/s12915-021-01165-3,
  23. https://doi.org/10.1038/s41598-026-54510-3,
  24. https://doi.org/10.1016/j.ajhg.2015.04.002,

📚 Additional Documentation

Notes

(CCDC28B-notes.md)

CCDC28B (Q9BUN5) — Gene Review Notes

Human gene, HGNC:28163, GeneID 79140, chromosome 1. Also known historically as MGC1203.
Small protein (200 aa, isoform 1), one C-terminal predicted coiled coil (158–183), two
disordered regions (1–49, 141–164). Part of the "Human BBSome" curation project.

Summary of biological role

CCDC28B is an accessory/modifier factor of the BBSome and ciliary trafficking machinery,
not a numbered structural BBS subunit. It was identified as a second-site (epistatic)
modifier of Bardet–Biedl syndrome (BBS). It localizes near centrosomes/basal bodies,
interacts with multiple BBSome subunits, and is required for normal ciliogenesis and
control of cilium length.

Provenance / key findings

  • Identified as a novel epistatic modifier locus (MGC1203/CCDC28B) for BBS; encodes a
    pericentriolar protein that interacts and colocalizes with BBS proteins. A heterozygous
    C430T variant enriched in BBS patients reduces steady-state mRNA; zebrafish mgc1203
    knockdown enhances the BBS-morphant developmental phenotype.
    PMID:16327777
    PMID:16327777

  • UniProt (from PMID:16327777): "Interacts with BBS1, BBS2, BBS4, BBS5, BBS6, BBS7 and
    TTC8/BBS8." Subcellular location: "Cytoplasm, cytoskeleton, microtubule organizing
    center, centrosome ... localizes near centrosomes and basal bodies."

  • First functional characterization: CCDC28B affects ciliogenesis in cultured cells and
    in vivo in zebrafish; homologs restricted to ciliated metazoa. Ccdc28b depletion in
    zebrafish causes defective ciliogenesis with hydrocephalus, left-right axis defects and
    renal impairment — hallmark ciliopathy phenotypes.
    PMID:23015189
    PMID:23015189
    PMID:23015189

  • Cilium length control via SIN1/mTORC2 axis: CCDC28B interacts with SIN1 (MAPKAP1),
    positively regulates mTORC2 assembly/stability/activity (not mTORC1), and controls
    ciliary length partly through SIN1 in an mTOR-independent manner. RICTOR depletion does
    NOT shorten cilia, separating the cilia-length role from canonical mTORC2 signaling.
    PMID:23727834
    PMID:23727834
    PMID:23727834

  • High-throughput binary interactome (Y2H) reports CCDC28B–ATRIP (Q8WXE1) interaction.
    PMID:25416956

GO annotation assessment

Existing GOA (6 stub entries; GOA TSV has more IPI WITH rows collapsed):

  1. GO:0005813 centrosome, IBA (GO_REF:0000033) — consistent with localization near
    centrosomes/basal bodies; phylogenetic inference. ACCEPT (non-core localization; the
    functional core is ciliogenesis/BBSome modulation).
  2. GO:0005813 centrosome, IEA (GO_REF:0000044, SubCell mapping) — same localization,
    electronic. Redundant with the experimental IDA. ACCEPT / KEEP_AS_NON_CORE.
  3. GO:0005515 protein binding, IPI (PMID:16327777, WITH BBS4 Q96RK4 etc.) — uninformative
    MF ("protein binding"). The underlying biology (BBSome subunit binding) is real and is
    better captured by BBSome localization / ciliogenesis terms. MARK_AS_OVER_ANNOTATED
    (protein binding is discouraged per curation guidelines; not a useful MF).
  4. GO:0005515 protein binding, IPI (PMID:25416956, WITH ATRIP Q8WXE1) — high-throughput
    binary interactome hit; uninformative term, single Y2H. OVER_ANNOTATED.
  5. GO:0005813 centrosome, IDA (PMID:16327777) — direct experimental localization near
    centrosomes. ACCEPT (core localization).
  6. GO:0060271 cilium assembly, IMP (PMID:23015189) — strongest functional annotation;
    IMP from loss-of-function in cells and zebrafish. ACCEPT (core function).

GO:0034464 (BBSome) is a cellular_component term for the complex; CCDC28B interacts with
BBSome subunits but is a modifier/accessory factor, not confirmed as a stable BBSome
component, so I do not propose a "part_of BBSome" CC annotation. Could be a question for
experts. Relevant process terms: regulation of cilium length (consider GO:0090660? — not
verified) — left as a suggested area.

📄 View Raw YAML

 
id: Q9BUN5
gene_symbol: CCDC28B
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: Coiled-coil domain-containing protein 28B (CCDC28B; historically MGC1203)
  is a small pericentriolar/basal-body-associated protein that acts as an accessory
  factor and genetic modifier of ciliary trafficking. It is required for normal ciliogenesis
  and for the control of cilium length, and it physically interacts with multiple
  Bardet-Biedl syndrome (BBSome) subunits, including BBS1, BBS2, BBS4, BBS5, BBS6,
  BBS7 and TTC8/BBS8, with which it colocalizes near centrosomes and basal bodies.
  Functionally, CCDC28B regulates cilium length in part through its interaction with
  SIN1/MAPKAP1 and acts as a positive regulator of mTOR complex 2 (mTORC2) assembly
  and activity; its effect on cilium length appears to be largely independent of canonical
  mTOR signaling. Depletion of the protein causes defective ciliogenesis in cultured
  cells and ciliopathy-like phenotypes in zebrafish (hydrocephalus, left-right axis
  defects, renal dysfunction). It is not a numbered structural BBS subunit but a modifier
  of BBSome-dependent ciliary function; homologous sequences are restricted to ciliated
  metazoa.
alternative_products:
- name: '1'
  id: Q9BUN5-1
- name: '2'
  id: Q9BUN5-3
  sequence_note: VSP_046552
existing_annotations:
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetically inferred centrosome localization. Consistent with the
      experimentally observed pericentriolar/basal-body localization of CCDC28B and
      with the localization of BBSome-associated proteins.
    action: ACCEPT
    reason: Localization is supported by direct experimental evidence (PMID:16327777)
      and is biologically coherent; however it is a subcellular-location annotation
      rather than the protein's core function (ciliogenesis/cilium-length control).
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation derived from UniProt subcellular-location vocabulary
      mapping. Redundant with the experimental IDA centrosome annotation from PMID:16327777.
    action: ACCEPT
    reason: The localization is correct and corroborated experimentally, though this
      electronic entry is redundant with the IDA evidence and is a non-core localization
      annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16327777
  qualifier: enables
  review:
    summary: IPI annotation capturing physical interactions with BBSome subunits (WITH
      includes BBS4/Q96RK4 and other BBS proteins). The underlying interactions are
      real and central to CCDC28B biology, but "protein binding" is an uninformative
      molecular-function term that conveys no specific activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: Per curation guidelines, the bare "protein binding" term should be avoided.
      The biologically meaningful content (binding to BBSome subunits near the basal
      body) is better represented by the ciliogenesis process annotation and by localization
      terms rather than by an uninformative MF term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: IPI annotation from a proteome-scale binary (Y2H) interactome map, supporting
      a CCDC28B-ATRIP (Q8WXE1) interaction. This is a single high-throughput binary
      hit and the term itself is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: "\"Protein binding\" is discouraged as uninformative, and this is a single\
      \ high-throughput interactome data point whose biological relevance to CCDC28B\
      \ function is unestablished."
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:16327777
  qualifier: located_in
  review:
    summary: Direct experimental evidence that CCDC28B is a pericentriolar protein
      localizing near centrosomes and basal bodies, where it colocalizes with BBS
      proteins. The falcon deep-research synthesis is consistent with this, describing
      CCDC28B as concentrating at the ciliary basal body (the microtubule-organizing
      center from which the primary cilium extends).
    action: ACCEPT
    reason: Well-supported direct localization evidence. This is a core localization
      for CCDC28B, consistent with its role at the base of the cilium.
    supported_by:
    - reference_id: file:human/CCDC28B/CCDC28B-deep-research-falcon.md
      supporting_text: CCDC28B concentrates at the basal body, the microtubule organizing
        center from which the primary cilium extends
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: IMP
  original_reference_id: PMID:23015189
  qualifier: involved_in
  review:
    summary: Loss-of-function (IMP) evidence that CCDC28B is required for ciliogenesis,
      shown both in cultured cells and in zebrafish, where depletion produces ciliopathy
      phenotypes (hydrocephalus, left-right axis defects, renal impairment). This
      is the best-supported functional annotation and reflects the gene's core biological
      role. Subsequent literature, as synthesized in the falcon deep-research report,
      reinforces that CCDC28B acts as a positive regulator of ciliogenesis and cilium
      length rather than a passive structural component.
    action: ACCEPT
    reason: Strong experimental loss-of-function evidence across cell and animal models;
      represents the core function of CCDC28B as a ciliogenesis factor.
    supported_by:
    - reference_id: PMID:23015189
      supporting_text: show it affects ciliogenesis both in cultured cells and in vivo
        in zebrafish
    - reference_id: file:human/CCDC28B/CCDC28B-deep-research-falcon.md
      supporting_text: CCDC28B positively regulates primary cilium length and promotes
        ciliogenesis in somatic cells
core_functions:
- description: Required for ciliogenesis; CCDC28B acts as an accessory factor at the
    base of the cilium that supports normal cilium assembly and the regulation of
    cilium length.
  supported_by:
  - reference_id: PMID:23015189
    supporting_text: show it affects ciliogenesis both in cultured cells and in vivo
      in zebrafish ... Depletion of Ccdc28b in zebrafish results in defective ciliogenesis
  - reference_id: PMID:23727834
    supporting_text: Ccdc28b regulates cilia length in vivo, at least in part, through
      its interaction with Sin1
- description: Physically associates with BBSome subunits (BBS1, BBS2, BBS4, BBS5,
    BBS6, BBS7, TTC8/BBS8) near centrosomes and basal bodies, functioning as a modifier/accessory
    factor of BBSome-dependent ciliary trafficking rather than as a structural BBSome
    subunit.
  supported_by:
  - reference_id: PMID:16327777
    supporting_text: MGC1203 encodes a pericentriolar protein that interacts and colocalizes
      with the BBS proteins
  - reference_id: file:human/CCDC28B/CCDC28B-deep-research-falcon.md
    supporting_text: 'While CCDC28B is not a core BBSome subunit, it functions as a BBS-associated
      modifier protein that supports BBSome-mediated ciliary homeostasis'
- description: Positively regulates mTOR complex 2 (mTORC2) assembly and activity through
    interaction with SIN1/MAPKAP1, with the cilium-length-control function being largely
    independent of canonical mTOR signaling.
  supported_by:
  - reference_id: PMID:23727834
    supporting_text: CCDC28B is a positive regulator of mTORC2, participating in its
      assembly/stability and modulating its activity, while not affecting mTORC1 function
proposed_new_terms: []
suggested_questions:
- question: Is CCDC28B a stable, stoichiometric component of the BBSome (GO:0034464),
    or a transient/peripheral interactor that modulates BBSome function without being
    part of the core complex?
- question: Does CCDC28B localize within the cilium proper (e.g., transition zone
    or axoneme) or is it restricted to the pericentriolar/basal-body region?
- question: What is the molecular activity by which CCDC28B controls cilium length,
    whether primarily through SIN1 scaffolding, through IFT/BBSome trafficking, or
    both?
suggested_experiments:
- description: Determine whether CCDC28B co-fractionates stoichiometrically with the
    BBSome by size-exclusion chromatography and quantitative mass spectrometry, to
    test BBSome membership versus accessory association.
- description: Use proximity labeling (BioID/TurboID) from CCDC28B in ciliated cells
    to define its in vivo interaction neighborhood at the basal body, transition zone,
    and cilium.
- description: Perform live-imaging of cilium assembly and length dynamics in CCDC28B-null
    cells with rescue by separation-of-function mutants (SIN1-binding versus BBSome-binding
    deficient) to dissect the mechanism of cilium-length control.
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: PMID:16327777
  title: Dissection of epistasis in oligogenic Bardet-Biedl syndrome.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Establishes CCDC28B (MGC1203) as a BBS modifier
      that interacts and colocalizes with BBS proteins and localizes pericentriolarly;
      supports the centrosome localization and BBSome-interaction annotations.
- id: PMID:23015189
  title: Characterization of CCDC28B reveals its role in ciliogenesis and provides
    insight to understand its modifier effect on Bardet-Biedl syndrome.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Provides the loss-of-function (IMP) evidence that
      CCDC28B is required for ciliogenesis in cells and zebrafish; supports the cilium
      assembly core-function annotation.
- id: PMID:23727834
  title: The Bardet-Biedl syndrome-related protein CCDC28B modulates mTORC2 function
    and interacts with SIN1 to control cilia length independently of the mTOR complex.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Establishes the SIN1/mTORC2 mechanism for cilium-length
      control; not currently the source of a GOA annotation but directly informs the
      core functions.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified high-throughput binary interactome study (CCDC28B-ATRIP).
      Supports only an uninformative "protein binding" annotation; biological relevance
      to CCDC28B ciliary function is unestablished.
- id: file:human/CCDC28B/CCDC28B-deep-research-falcon.md
  title: Falcon deep research report for CCDC28B
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: UNVERIFIED
    review_notes: LLM-synthesized deep-research report (Edison/Falcon). It corroborates
      the well-established, CCDC28B-specific picture already in this review - a non-enzymatic
      coiled-coil regulatory/adaptor protein that positively regulates ciliogenesis and
      cilium length, localizes to the ciliary basal body/axoneme, and acts as a BBS-associated
      modifier rather than a core BBSome subunit. These specific claims are consistent
      with the primary literature (PMID:16327777, PMID:23015189, PMID:23727834). Other
      assertions in the report are weaker, secondary, or generalize from BBSome/BBS-core
      biology rather than from CCDC28B-specific data and are NOT used to drive annotation
      changes here, including KIF5B-regulated nuclear accumulation/possible nuclear roles,
      BBS/CCT chaperonin coupling, regulatory-B-cell expression, brain-aging expression
      dynamics, rat hypertension/senescence SNPs, and the CCDC28A paralog characterization.
      Correctness UNVERIFIED because the report cites only internal keys/DOIs (no PMIDs)
      and is LLM-generated synthesis.