Affinage

Showing SDCCAG8 — NPHP10 is a alias.

SDCCAG8

Serologically defined colon cancer antigen 8 · UniProt Q86SQ7

Length
713 aa
Mass
82.7 kDa
Annotated
2026-06-10
17 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SDCCAG8 is an integral centrosomal and centriolar satellite protein that organizes pericentriolar material and supports ciliogenesis across multiple tissues (PMID:12559564, PMID:25088364, PMID:27224062). It is a stable centrosomal component throughout the cell cycle, with its C-terminal coiled-coil region mediating both homo-oligomerization and the centrosomal targeting that is obligatory for cilium formation (PMID:12559564, PMID:35131266). Through coiled-coil domains 5–7, SDCCAG8 directly binds the centriolar satellite scaffold PCM1 and co-traffics with it, and this interaction is required to stabilize PCM1 and recruit downstream satellite components such as BBS4 and CEP131 (PMID:25088364, PMID:40801568). SDCCAG8 additionally engages the centriolar/satellite proteins OFD1 and AZI1, endosomal sorting factors RABEP2 and ERC1, non-muscle myosin motors MYH9/MYH10/MYH14, and the ciliopathy kinases ICK/CILK1 and MAK, coordinating recruitment of γ-tubulin and pericentrin to the centrosome, ciliary protein trafficking, and Hedgehog signaling (PMID:25088364, PMID:27224062, PMID:35131266). Loss of SDCCAG8 produces tissue-specific consequences: rhodopsin/phototransduction protein mislocalization and photoreceptor degeneration in the retina, renal pathology accompanied by elevated DNA damage response signaling (γH2AX, phospho-ATM), centrosome–nucleus decoupling with defective cortical neuronal migration, and disrupted centriolar satellite integrity causing failed sperm flagellum biogenesis (PMID:24722439, PMID:25088364, PMID:40801568). Truncating SDCCAG8 mutations modeling human Bardet-Biedl and Senior-Løken syndromes impair ciliogenesis and cause the full ciliopathy spectrum including cleft palate, polydactyly, retinal degeneration, and cystic kidney (PMID:35131266, PMID:35503560).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2003 Medium

    Established that SDCCAG8 is a bona fide structural component of the centrosome rather than a microtubule-associated factor, and mapped the C-terminal coiled-coil as the self-association and targeting module.

    Evidence Immunofluorescence with nocodazole treatment, yeast two-hybrid, and N-/C-terminal truncation constructs in fibroblasts and U2-OS cells

    PMID:12559564

    Open questions at the time
    • No interacting partners identified
    • Functional role at the centrosome not addressed
    • In vivo relevance untested
  2. 2010 High

    Linked SDCCAG8 to ciliopathy biology by placing it at centrioles in direct contact with OFD1 and showing knockdown causes renal cysts and polarity defects in vivo.

    Evidence OFD1 pulldown/Co-IP, zebrafish morpholino knockdown with kidney/axis phenotypes, 3D renal cell polarity assay

    PMID:20835237

    Open questions at the time
    • Molecular consequence of OFD1 binding unresolved
    • Morpholino specificity not genetically confirmed
    • Connection to cilium assembly not yet mechanistic
  3. 2012 Medium

    Demonstrated tissue-specific ciliary targeting, showing RPGRIP1 is required to deliver SDCCAG8 to the photoreceptor connecting cilium but not in kidney.

    Evidence Immunofluorescence and subcellular fractionation in Rpgrip1-null mouse retina versus kidney

    PMID:22825473

    Open questions at the time
    • Direct RPGRIP1–SDCCAG8 interaction not shown
    • Mechanism of ER-shift upon mislocalization unknown
    • Does not explain renal targeting route
  4. 2014 High

    Defined distinct organ-level disease mechanisms — retinal rhodopsin mislocalization versus a DNA-damage-response-associated renal pathology without global ciliary defects.

    Evidence Sdccag8 gene-trap mouse; rhodopsin IF, γH2AX/phospho-ATM Western blot, cell cycle flow cytometry across retina and kidney

    PMID:24722439

    Open questions at the time
    • Causal link between SDCCAG8 loss and DDR activation unexplained
    • Why kidney lacks global ciliary defect unresolved
  5. 2014 High

    Showed SDCCAG8 organizes pericentriolar material and couples the centrosome to the nucleus, explaining a neuronal migration phenotype, and identified PCM1 as a physical co-trafficking partner.

    Evidence shRNA and loss-of-function allele in mouse cortex; γ-tubulin/pericentrin IF; PCM1 Co-IP/co-trafficking; in utero electroporation migration assay

    PMID:25088364

    Open questions at the time
    • Domain mediating PCM1 binding not yet mapped
    • Mechanism of centrosome–nucleus coupling not defined
  6. 2016 Medium

    Expanded the SDCCAG8 interactome by affinity proteomics and demonstrated it is required for ciliogenesis and Hedgehog signaling, acting in part through RABEP2 recruitment.

    Evidence BioID/AP-MS interactome; siRNA of SDCCAG8 and RABEP2 in hTERT-RPE1; cilia IF and Hedgehog reporter assay

    PMID:27224062

    Open questions at the time
    • Direct versus indirect nature of most interactions unresolved
    • How myosin motors contribute mechanistically unknown
  7. 2019 Medium

    Identified transcriptional control of SDCCAG8 by SOX11 and a pro-tumorigenic role in HNSCC, extending SDCCAG8 biology beyond ciliopathy.

    Evidence ChIP, luciferase reporter with SOX11 DNA-binding mutant, shRNA knockdown and rescue overexpression, quantitative proteomics in HNSCC cells

    PMID:30922366

    Open questions at the time
    • Mechanism by which SDCCAG8 promotes proliferation/invasion not defined
    • Cilia-dependence of cancer phenotype unaddressed
  8. 2020 Medium

    Confirmed via CRISPR knockout that SDCCAG8 is required for ciliogenesis and cilium-dependent signaling and is needed for neuronal differentiation and migration with a neurodevelopmental transcriptomic signature.

    Evidence CRISPR genome editing; primary cilia IF; RNA-seq; neuronal migration and differentiation assays

    PMID:31868218

    Open questions at the time
    • Direct targets driving transcriptomic changes unknown
    • Link between cilia loss and differentiation defect not mechanistically dissected
  9. 2022 High

    Mapped the C-terminal region as essential for centrosomal localization and cilia formation and identified ICK/CILK1 and MAK as C-terminal binding partners, connecting SDCCAG8 to ciliary trafficking kinases.

    Evidence Co-IP of SDCCAG8-C with ICK/CILK1 and MAK; CRISPR stop-codon knock-in mouse with cleft palate, polydactyly, retinal, renal and spermatogenesis defects; localization IF

    PMID:35131266

    Open questions at the time
    • Whether kinases phosphorylate SDCCAG8 unknown
    • Structural basis of C-terminal interactions undefined
  10. 2022 Medium

    Validated patient-mimicking BBS/SLS truncating mutations as causing ciliogenesis failure across photoreceptors, renal epithelium and MEFs with phototransduction protein mislocalization.

    Evidence CRISPR/Cas9 knock-in mouse models; cilia and phototransduction protein IF; retina and kidney histology

    PMID:35503560

    Open questions at the time
    • Genotype–phenotype correlation across mutations not quantified
    • Mechanism of protein mislocalization secondary to degeneration unclear
  11. 2025 Medium

    Resolved the PCM1-binding determinant to coiled-coil domains 5–7 and showed these are required to stabilize PCM1 and recruit BBS4 and CEP131 to satellites, explaining a sperm flagellum (MMAF) phenotype.

    Evidence Domain-mapped Co-IP of SDCCAG8 with PCM1; Sdccag8 truncation mouse; PCM1/BBS4/CEP131 IF in spermatids; sperm morphology

    PMID:40801568

    Open questions at the time
    • Whether CC5–7 binding mechanism generalizes beyond spermatids untested
    • Direct versus PCM1-bridged recruitment of BBS4/CEP131 not distinguished
  12. 2025 Medium

    Provided a therapeutic proof-of-concept by using ASOs to suppress cryptic exon inclusion and restore SDCCAG8 protein in patient fibroblasts with biallelic intronic mutations.

    Evidence ASO screen in patient-derived fibroblasts; RT-PCR splice assay, RNA-seq, Western blot (preprint)

    PMID:41279107

    Open questions at the time
    • Not peer-reviewed
    • Functional rescue of ciliary phenotype not demonstrated
    • In vivo efficacy untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SDCCAG8 integrates its many partners into a single biochemical mechanism — and whether its centrosomal scaffolding role is regulated by the ICK/CILK1 and MAK kinases it binds — remains unresolved.
  • No structure of SDCCAG8 or its complexes
  • Whether SDCCAG8 is a kinase substrate unknown
  • Hierarchy among OFD1, PCM1, RABEP2 and myosin interactions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005815 microtubule organizing center 3 GO:0005929 cilium 3
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 1
Partners
AZI1ICK/CILK1MAKMYH10MYH9OFD1PCM1RABEP2
Complex memberships
centriolar satellitescentrosome/pericentriolar material

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 SDCCAG8 (CCCAP) localizes to centrosomes during both interphase and mitosis, and this localization is not disrupted by nocodazole-induced microtubule depolymerization, indicating it is an integral centrosomal component rather than a microtubule-associated protein. The C-terminal coiled-coil domain is capable of homo-oligomerization, and truncations of either the N- or C-terminus abolish centrosomal localization. Immunofluorescence localization in fibroblasts and U2-OS cells, nocodazole treatment, yeast two-hybrid for homo-oligomerization, N- and C-terminal truncation constructs Gene Medium 12559564
2010 SDCCAG8 localizes at both centrioles and directly interacts with OFD1 (oral-facial-digital syndrome 1 protein). Depletion of sdccag8 in zebrafish causes kidney cysts and body axis defects; depletion in 3D renal cell cultures induces cell polarity defects. Immunofluorescence localization, direct protein interaction assay (pulldown/Co-IP with OFD1), zebrafish morpholino knockdown, 3D renal cell culture with polarity readout Nature genetics High 20835237
2012 SDCCAG8 localizes to the photoreceptor connecting cilium, and its ciliary localization is strongly decreased (shifted to ER-associated membrane fraction) in Rpgrip1-null photoreceptors, while NPHP4, RPGR, and SDCCAG8 expression levels remain unaffected. This demonstrates that RPGRIP1 is required for ciliary targeting of SDCCAG8 specifically in photoreceptors but not in kidney cells. Immunofluorescence and subcellular fractionation in Rpgrip1(nmf247) mouse retina and kidney; co-localization with centrin-2 and acetylated-α-tubulin Cell death & disease Medium 22825473
2014 Loss of Sdccag8 in a gene-trap mouse causes rhodopsin mislocalization in photoreceptors, reduced cone cell numbers, and progressive vision loss. Renal pathology is associated with elevated DNA damage response signaling (elevated γH2AX and phosphorylated ATM) and cell cycle abnormalities, but no global ciliary defects in kidneys, indicating tissue-specific disease mechanisms. Sdccag8 gene-trap mouse model; immunofluorescence for rhodopsin; Western blot for γH2AX and phospho-ATM; cell cycle profiling by flow cytometry Journal of the American Society of Nephrology : JASN High 24722439
2014 SDCCAG8 regulates centrosomal accumulation of pericentriolar material (PCM) proteins γ-tubulin and pericentrin in newborn cortical neurons. Suppression of Sdccag8 decouples the centrosome from the nucleus and impairs microtubule organization, leading to defective neuronal migration in the developing cortex. SDCCAG8 physically interacts and co-traffics with PCM1 (pericentriolar material 1), a centriolar satellite scaffold protein required for centrosomal protein targeting. shRNA knockdown and loss-of-function allele in mouse cortex; immunofluorescence for γ-tubulin and pericentrin; Co-IP/co-trafficking assay with PCM1; in utero electroporation for migration assay Neuron High 25088364
2016 SDCCAG8 interacts with centriolar satellite proteins OFD1 and AZI1, endosomal sorting complex proteins RABEP2 and ERC1, and non-muscle myosin motor proteins MYH9, MYH10, and MYH14 at the centrosome, as identified by affinity proteomics. SDCCAG8 is required for ciliogenesis and Hedgehog signaling in cell culture. SDCCAG8 regulates RABEP2 localization at the centrosome; siRNA knockdown of RABEP2 independently causes defective ciliogenesis. Affinity proteomics (BioID/AP-MS) for interaction partners; siRNA knockdown of SDCCAG8 and RABEP2 in hTERT-RPE1 cells; immunofluorescence for cilia and RABEP2; Hedgehog signaling reporter assay PloS one Medium 27224062
2019 SOX11 transcription factor directly binds the SDCCAG8 gene promoter and drives SDCCAG8 expression in HNSCC cells; wild-type SOX11 (but not a DNA-binding mutant) induces SDCCAG8 promoter activity and protein expression. SDCCAG8 knockdown recapitulates the inhibitory effects of SOX11 knockdown on HNSCC cell proliferation, migration, and invasion, and SDCCAG8 overexpression partially rescues SOX11 knockdown phenotypes. ChIP assay, luciferase reporter assay, rescue overexpression experiments, shRNA knockdown, quantitative proteomics Journal of experimental & clinical cancer research : CR Medium 30922366
2020 Genome editing to disrupt SDCCAG8 causes defects in primary ciliogenesis and cilium-dependent signaling in cells. SDCCAG8-deficient neuronal cells exhibit impaired migration and neuronal differentiation. Transcriptomic analysis of SDCCAG8-deficient cells identifies differentially expressed genes enriched in neurodevelopmental processes (neuron generation, synapse organization). CRISPR genome editing of SDCCAG8; immunofluorescence for primary cilia; transcriptomic (RNA-seq) analysis; neuronal migration and differentiation assays Human molecular genetics Medium 31868218
2022 The C-terminal region of SDCCAG8 (Sdccag8-C) is essential for SDCCAG8 localization to centrosomes and for cilia formation. Sdccag8-C interacts with ciliopathy kinases ICK/CILK1 and MAK, which regulate ciliary protein trafficking and cilia length. Truncation of Sdccag8-C in mice (CRISPR knock-in) causes defective ciliogenesis and ciliopathy phenotypes (cleft palate, polydactyly, retinal degeneration, cystic kidney, spermatogenesis defects). Co-immunoprecipitation of SDCCAG8-C with ICK/CILK1 and MAK; CRISPR-mediated stop codon knock-in mouse; immunofluorescence for cilia and centrosomal localization in cultured cells and mouse tissues The Journal of biological chemistry High 35131266
2022 Knock-in mice carrying human BBS- or SLS-associated truncating Sdccag8 mutations show impaired cilia formation in photoreceptors, renal epithelial cells, and mouse embryonic fibroblasts, along with phototransduction protein mislocalization outside outer segments after photoreceptor degeneration, demonstrating that SDCCAG8 plays an essential role in ciliogenesis. CRISPR/Cas9 knock-in mouse models; immunofluorescence for cilia morphology and phototransduction protein localization; histology of retina and kidney Zoological research Medium 35503560
2025 SDCCAG8 protein, through its coiled-coil (CC) domains 5–7, directly interacts with PCM1 (the centriolar satellite scaffold protein). Absence of CC domains 5–7 in mutant spermatids destabilizes PCM1 and prevents recruitment of BBS4 and CEP131 to centriolar satellites, causing defective sperm flagellum biogenesis and male infertility (MMAF phenotype). SDCCAG8 localizes to the manchette and centrosomal region in spermatids. Co-immunoprecipitation of SDCCAG8 with PCM1 via CC domains 5–7; Sdccag8 truncation mouse model; immunofluorescence for PCM1, BBS4, CEP131 localization in spermatids; sperm morphology analysis Cells Medium 40801568
2025 Antisense oligonucleotides (ASOs) targeting the cryptic exon 7a/7a' splice site in SDCCAG8 intron 7 restore wild-type splicing between exons 7 and 8 and rescue SDCCAG8 protein expression (to ~40% of wild-type) in patient-derived fibroblasts carrying biallelic intronic mutations that cause cryptic exon inclusion with premature termination codons. ASO screen in patient-derived fibroblasts; RT-PCR splice assay; RNA sequencing; Western blotting for SDCCAG8 protein restoration bioRxivpreprint Medium 41279107

Source papers

Stage 0 corpus · 17 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nature genetics 269 20835237
2011 Mutations in SDCCAG8/NPHP10 Cause Bardet-Biedl Syndrome and Are Associated with Penetrant Renal Disease and Absent Polydactyly. Molecular syndromology 67 22190896
2014 Renal-retinal ciliopathy gene Sdccag8 regulates DNA damage response signaling. Journal of the American Society of Nephrology : JASN 62 24722439
2014 SDCCAG8 regulates pericentriolar material recruitment and neuronal migration in the developing cortex. Neuron 46 25088364
2012 Selective loss of RPGRIP1-dependent ciliary targeting of NPHP4, RPGR and SDCCAG8 underlies the degeneration of photoreceptor neurons. Cell death & disease 42 22825473
2019 Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8. Journal of experimental & clinical cancer research : CR 31 30922366
2003 Identification and characterization of the novel centrosome-associated protein CCCAP. Gene 25 12559564
2016 SDCCAG8 Interacts with RAB Effector Proteins RABEP2 and ERC1 and Is Required for Hedgehog Signaling. PloS one 23 27224062
2022 The carboxyl-terminal region of SDCCAG8 comprises a functional module essential for cilia formation as well as organ development and homeostasis. The Journal of biological chemistry 14 35131266
2020 Altered gene regulation as a candidate mechanism by which ciliopathy gene SDCCAG8 contributes to schizophrenia and cognitive function. Human molecular genetics 12 31868218
2020 A novel splice site mutation in the SDCCAG8 gene in an Iranian family with Bardet-Biedl syndrome. International ophthalmology 6 32926352
2019 Rapidly Progressive Nephronophthisis in a 2-Year-Old Boy with a Homozygous SDCCAG8 Mutation. The Tohoku journal of experimental medicine 5 31534065
2022 Characterization of two novel knock-in mouse models of syndromic retinal ciliopathy carrying hypomorphic Sdccag8 mutations. Zoological research 4 35503560
2022 Locally advanced undifferentiated small round cell sarcoma of the lung with novel SDCCAG8-AKT3 fusion and type II tumor immunity in the microenvironment: a rare case report. Translational lung cancer research 3 36090644
2025 Loss of C-Terminal Coiled-Coil Domains in SDCCAG8 Impairs Centriolar Satellites and Causes Defective Sperm Flagellum Biogenesis and Male Fertility. Cells 2 40801568
2021 Genetic variants of SDCCAG8 and MAGI2 in mitosis-related pathway genes are independent predictors of cutaneous melanoma-specific survival. Cancer science 2 34375487
2025 Splice-switching antisense oligonucleotides correct cryptic exon inclusion and restore SDCCAG8 protein in Bardet-Biedl Syndrome. bioRxiv : the preprint server for biology 0 41279107

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