Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Concise GO annotation research for human ANKS6 / UniProt Q68DC2. Focus only on GO-relevant evidence: ANKS6/SamCystin as a ciliary inversin-compartment scaffold or molecular adaptor; interactions with NEK8, INVS, NPHP3, ANKS3, BICC1; protein kinase binding versus generic protein binding; SAM-domain-mediated complex assembly; localization to ciliary inversin compartment, cilium and cytoplasm; role in nephronophthisis/cystic kidney disease, renal tubule/nephron development; regulation of canonical Wnt/beta-catenin signaling, Hippo/YAP signaling, cAMP pathways, and ciliopathy phenotypes. Include caveats for over-broad developmental/disease terms and high-throughput interactome protein binding annotations. Include PMID/DOI citations and keep under 1500 words.

Concise GO-annotation research report: Human ANKS6 / SamCystin (UniProt Q68DC2; NPHP16)

Scope and framing (GO-relevant concepts)

ANKS6 is an ankyrin-repeat + SAM-domain protein best supported as a ciliary inversin-compartment (INVc/InvsC) scaffold/adaptor that (i) forms a specific functional subcomplex with the ciliary kinase NEK8, and (ii) participates in a SAM-domain multivalent assembly network with ANKS3 and BICC1 that tunes higher-order complex formation (and, indirectly, RNA/cAMP-related outputs). Mechanistically, ANKS6 sits within a hierarchical module: INVS is upstream/core for INVc assembly, ANKS6–NEK8 are downstream to recruit/concentrate NPHP3. (bennett2020novelfibrillarstructure pages 1-4, bennett2020novelfibrillarstructure pages 11-13, hoff2013anks6isa pages 1-2)

1) Key GO concepts and definitions (current understanding)

Inversin compartment (INVc/InvsC): A proximal-cilium (periaxonemal) subcompartment containing INVS, ANKS6, NEK8, and NPHP3. Superresolution and genetic dissection support that INVS is the structural determinant, while NEK8 and ANKS6 depend on INVS for localization and together act to localize/concentrate NPHP3. (bennett2020novelfibrillarstructure pages 1-4, bennett2020novelfibrillarstructure pages 11-13)

ANKS6 as kinase-binding adaptor vs generic ‘protein binding’: Several datasets place ANKS6 in interactome-like networks, but high-confidence GO MF annotation should emphasize specific, domain-mapped binding to a protein kinase (NEK8) and its functional consequence (NEK8 activation/phosphorylation), rather than broad “protein binding.” (czarnecki2015anks6isthe pages 1-2, smith2019themechanisticfunctiona pages 56-59, hoff2013anks6isa pages 1-2)

SAM-domain complex assembly: ANKS6 SAM-domain integrity is required for selective interactions (notably with ANKS3 and/or indirectly with BICC1 via ANKS3), and cystic mutations in the SAM region disrupt these assemblies. (bakey2015thesamdomain pages 1-2, clark2020invivocharacterisationa pages 34-38, rothe2018crystalstructureof pages 10-11)

2) Most recent developments (prioritizing 2023–2024)

ANKS6→ANKS3 remodeling licenses BICC1 assemblies (2023): In vitro reconstitution and AlphaFold-guided complex models support that ANKS6 binds ANKS3 with higher affinity than BICC1, sequestering ANKS3’s SAM and thereby freeing BICC1 SAM to self-polymerize, promoting BICC1 RNP assembly. This provides updated mechanistic evidence for SAM-domain-mediated complex assembly and “adaptor/scaffold” roles involving ANKS6–ANKS3–BICC1. (Published 2023-09; DOI:10.1371/journal.pbio.3002302; https://doi.org/10.1371/journal.pbio.3002302) (rothe2023bicc1ribonucleoproteincomplexes pages 1-2)

ANKS6/InvsC metrics in ciliary assays (2024 preprint): A 2024 bioRxiv study includes experimental pipelines quantifying the inversin-compartment size using ANKS6/NEK8/INVS staining relative to total cilium length and uses co-IP/colocalization analysis. In the provided excerpt, these details are methodological (results not shown), so they currently support that ANKS6 localization/InvsC parameters were directly measured, but cannot be used as outcome evidence without the results sections. (Posted 2024-04; DOI:10.1101/2024.04.18.588747; https://doi.org/10.1101/2024.04.18.588747) (mahuzier2024theanks3bicc1protein pages 20-24, mahuzier2024theanks3bicc1protein pages 1-5)

Ciliopathy model synthesis (2024 review): A 2024 review of the Han:SPRD rat model reiterates ANKS6/SamCystin relevance to cystogenesis and summarizes pathway connections including Hippo/YAP (secondary source). Use for context, not primary GO evidence. (Published 2024-02; DOI:10.3390/biomedicines12020362; https://doi.org/10.3390/biomedicines12020362) (kofotolios2024thehansprdrat pages 7-8)

3) Core GO evidence by aspect (CC, MF, BP)

A. Cellular Component (CC)

Ciliary inversin compartment / proximal cilium:
* High-confidence localization and dependency evidence comes from superresolution imaging plus CRISPR knockouts in human RPE1 cells, supporting that ANKS6 is an INVc component and depends on INVS for localization; ANKS6 and NEK8 are required downstream to properly localize/concentrate NPHP3. (bennett2020novelfibrillarstructure pages 1-4, bennett2020novelfibrillarstructure pages 11-13)
* Additional support that ANKS6 “localizes to the proximal cilium” and is part of the NEK8–INVS–NPHP3 nephronophthisis module comes from human genetics plus functional work. (Published 2013-06; DOI:10.1038/ng.2681; https://doi.org/10.1038/ng.2681) (hoff2013anks6isa pages 1-2)

Primary cilium (broader): Renal cilium localization and “Inv compartment” framing supports primary cilium annotation as a parent CC term. (nakajima2018theinvcompartment pages 1-2, bakey2015thesamdomain pages 1-2)

Cytoplasm (qualified): There is evidence that INV proteins can exist outside cilia and that ANKS6 participates in cytoplasmic complexes (especially with ANKS3/BICC1 in co-expression assays), but this is weaker and should be annotated cautiously compared with ciliary localization. (nakajima2018theinvcompartment pages 1-2, clark2020invivocharacterisationa pages 34-38)

Visual evidence: Bennett et al. provide figure-level support showing co-localization and a hierarchical dependency model for INVc components (INVS, ANKS6, NEK8, NPHP3). (bennett2020novelfibrillarstructure media 833c1b6b, bennett2020novelfibrillarstructure media af0b91fd)

B. Molecular Function (MF)

Protein kinase binding (specific): ANKS6 binds the NEK8 kinase domain (domain-mapped interaction), supporting “protein kinase binding” over generic “protein binding.” (Published 2015-01; DOI:10.1038/ncomms7023; https://doi.org/10.1038/ncomms7023) (czarnecki2015anks6isthe pages 1-2)

Kinase activation/regulation (NEK8): Cell-based kinase assays and genetics support that ANKS6 stimulates NEK8 autophosphorylation/kinase output and is also phosphorylated in a NEK8-dependent manner; disease-relevant alleles reducing ANKS6–NEK8 interaction impair NEK8 activation. (czarnecki2015anks6isthe pages 1-2)

SAM-domain-mediated complex assembly / adaptor function: SAM-domain mutations (e.g., PKD-associated) disrupt specific interactions (e.g., with ANKS3 or BICC1 depending on allele/model), and reconstitution studies show ANKS6 promotes higher-order assemblies that recruit other partners. (bakey2015thesamdomain pages 1-2, rothe2018crystalstructureof pages 10-11, clark2020invivocharacterisationa pages 34-38)

C. Biological Process (BP)

Organization of the inversin compartment / intraciliary signaling center: The INVc acts as an intraciliary center where INV and NPHP3 cooperate to promote NEK8-dependent phosphorylation of ANKS6, tying ANKS6 to intraciliary signal activation rather than only “ciliogenesis.” (Published 2018-05; DOI:10.1016/j.kint.2017.11.016; https://doi.org/10.1016/j.kint.2017.11.016) (nakajima2018theinvcompartment pages 1-2)

Renal tubule/nephron development (avoid over-broad terms): Knockdown experiments in zebrafish/Xenopus plus human genetics link ANKS6 dysfunction to renal developmental phenotypes consistent with nephronophthisis-spectrum ciliopathy. Prefer specific developmental process terms (e.g., renal tubule morphogenesis) over broad “kidney development” when curating. (hoff2013anks6isa pages 1-2)

Ciliopathy phenotypes (context, not GO BP): Human families with ANKS6 mutations show nephronophthisis and multisystem ciliopathy phenotypes (including laterality defects). These support biological-process annotations around cilium-dependent morphogenesis/signaling, but disease names themselves are not GO processes. (hoff2013anks6isa pages 1-2, bakey2015thesamdomain pages 1-2)

Pathway links (Wnt/β-catenin, Hippo/YAP, cAMP):
* Wnt signaling: INVc/InvsC is repeatedly stated to control canonical Wnt/Wnt-PCP, but the provided 2024 preprint excerpt is not outcome evidence; treat as indirect unless supported by direct ANKS6 perturbation assays in the cited work. (mahuzier2024theanks3bicc1protein pages 1-5)
* Hippo/YAP: A primary pathway study reports ANKS6 affects YAP/TAZ/TEAD activity in a developmental context; however, this is not kidney-specific and should not be generalized to all ANKS6 biology without additional corroboration. (kofotolios2024thehansprdrat pages 7-8)
* cAMP: Newer mechanistic work ties ANKS6 to the ANKS3–BICC1 network that controls BICC1 polymerization/RNP behavior and discusses BICC1-mediated control of Adcy6/cAMP; ANKS6 effects appear indirect via ANKS3 remodeling. (rothe2023bicc1ribonucleoproteincomplexes pages 1-2)

4) Applications and real-world implementations

Translational use is mainly interpretive/diagnostic rather than therapeutic: Mechanistic INVc and SAM-network insights are used to interpret ciliopathy genetics (e.g., ANKS6/NEK8/INVS/NPHP3 modules) and to select/validate preclinical models of cystic kidney disease and laterality defects. (hoff2013anks6isa pages 1-2, bakey2015thesamdomain pages 1-2, czarnecki2015anks6isthe pages 1-2)

5) Expert caveats for GO curation

1. Prefer specific MF terms (protein kinase binding; kinase activator/regulator) where domain mapping and functional assays exist, particularly for ANKS6–NEK8. (czarnecki2015anks6isthe pages 1-2, smith2019themechanisticfunctiona pages 56-59)
2. De-emphasize generic “protein binding” when evidence is largely AP-MS/network-based without orthogonal validation. (hoff2013anks6isa pages 1-2)
3. Use appropriately granular BP terms: “renal tubule development/morphogenesis” and “cilium-dependent signaling/compartment organization” are better supported than broad “development” terms or disease-name processes. (hoff2013anks6isa pages 1-2, nakajima2018theinvcompartment pages 1-2)
4. Treat preprints/reviews as provisional/secondary for direct GO assertions unless primary results are explicitly available in the excerpted evidence. (mahuzier2024theanks3bicc1protein pages 1-5, kofotolios2024thehansprdrat pages 7-8)

GO-evidence mapping table

Table: This table summarizes GO-relevant evidence for human ANKS6/SamCystin across cellular component, molecular function, and biological process categories. It highlights the strongest mechanistic support and flags where annotations should remain cautious because evidence is indirect, overexpression-based, high-throughput, or review/preprint derived.

Key primary sources (with dates and URLs)

• Hoff et al., 2013-06 (Nature Genetics): https://doi.org/10.1038/ng.2681 (hoff2013anks6isa pages 1-2)
• Czarnecki et al., 2015-01 (Nature Communications): https://doi.org/10.1038/ncomms7023 (czarnecki2015anks6isthe pages 1-2)
• Bakey et al., 2015-08 (Kidney International): https://doi.org/10.1038/ki.2015.122 (bakey2015thesamdomain pages 1-2)
• Nakajima et al., 2018-05 (Kidney International): https://doi.org/10.1016/j.kint.2017.11.016 (nakajima2018theinvcompartment pages 1-2)
• Rothé et al., 2018-02 (Structure): https://doi.org/10.1016/j.str.2017.12.002 (rothe2018crystalstructureof pages 10-11)
• Bennett et al., 2020-03 (Molecular Biology of the Cell): https://doi.org/10.1091/mbc.e19-09-0499 (bennett2020novelfibrillarstructure pages 1-4, bennett2020novelfibrillarstructure pages 11-13)
• Rothé et al., 2023-09 (PLOS Biology): https://doi.org/10.1371/journal.pbio.3002302 (rothe2023bicc1ribonucleoproteincomplexes pages 1-2)
• Mahuzier et al., 2024-04 (bioRxiv preprint): https://doi.org/10.1101/2024.04.18.588747 (mahuzier2024theanks3bicc1protein pages 20-24, mahuzier2024theanks3bicc1protein pages 1-5)

References

1. (bennett2020novelfibrillarstructure pages 1-4): Henrietta W. Bennett, Anna-Karin Gustavsson, Camille A. Bayas, Petar N. Petrov, Nancie Mooney, W. E. Moerner, and Peter K. Jackson. Novel fibrillar structure in the inversin compartment of primary cilia revealed by 3d single-molecule superresolution microscopy. Molecular Biology of the Cell, 31:619-639, Mar 2020. URL: https://doi.org/10.1091/mbc.e19-09-0499, doi:10.1091/mbc.e19-09-0499. This article has 60 citations and is from a domain leading peer-reviewed journal.

2. (bennett2020novelfibrillarstructure pages 11-13): Henrietta W. Bennett, Anna-Karin Gustavsson, Camille A. Bayas, Petar N. Petrov, Nancie Mooney, W. E. Moerner, and Peter K. Jackson. Novel fibrillar structure in the inversin compartment of primary cilia revealed by 3d single-molecule superresolution microscopy. Molecular Biology of the Cell, 31:619-639, Mar 2020. URL: https://doi.org/10.1091/mbc.e19-09-0499, doi:10.1091/mbc.e19-09-0499. This article has 60 citations and is from a domain leading peer-reviewed journal.

3. (hoff2013anks6isa pages 1-2): Sylvia Hoff, Jan Halbritter, Daniel Epting, Valeska Frank, Thanh-Minh T Nguyen, Jeroen van Reeuwijk, Christopher Boehlke, Christoph Schell, Takayuki Yasunaga, Martin Helmstädter, Miriam Mergen, Emilie Filhol, Karsten Boldt, Nicola Horn, Marius Ueffing, Edgar A Otto, Tobias Eisenberger, Mariet W Elting, Joanna A E van Wijk, Detlef Bockenhauer, Neil J Sebire, Søren Rittig, Mogens Vyberg, Troels Ring, Martin Pohl, Lars Pape, Thomas J Neuhaus, Neveen A Soliman Elshakhs, Sarah J Koon, Peter C Harris, Florian Grahammer, Tobias B Huber, E Wolfgang Kuehn, Albrecht Kramer-Zucker, Hanno J Bolz, Ronald Roepman, Sophie Saunier, Gerd Walz, Friedhelm Hildebrandt, Carsten Bergmann, and Soeren S Lienkamp. Anks6 is a central component of a nephronophthisis module linking nek8 to invs and nphp3. Nature genetics, 45:951-956, Jun 2013. URL: https://doi.org/10.1038/ng.2681, doi:10.1038/ng.2681. This article has 237 citations and is from a highest quality peer-reviewed journal.

4. (czarnecki2015anks6isthe pages 1-2): Peter G. Czarnecki, George C. Gabriel, Danielle K. Manning, Mikhail Sergeev, Kristi Lemke, Nikolai T. Klena, Xiaoqin Liu, Yu Chen, You Li, Jovenal T. San Agustin, Maija K. Garnaas, Richard J. Francis, Kimimasa Tobita, Wolfram Goessling, Gregory J. Pazour, Cecilia W. Lo, David R. Beier, and Jagesh V. Shah. Anks6 is the critical activator of nek8 kinase in embryonic situs determination and organ patterning. Nature communications, 6:6023-6023, Jan 2015. URL: https://doi.org/10.1038/ncomms7023, doi:10.1038/ncomms7023. This article has 66 citations and is from a highest quality peer-reviewed journal.

5. (smith2019themechanisticfunctiona pages 56-59): DC Smith. The mechanistic function of bicc1: its role in adpkd pathogenesis. Unknown journal, 2019.

6. (bakey2015thesamdomain pages 1-2): Zeineb Bakey, Marie-Thérèse Bihoreau, Rémi Piedagnel, Laure Delestré, Catherine Arnould, Alexandre d'Hotman de Villiers, Olivier Devuyst, Sigrid Hoffmann, Pierre Ronco, Dominique Gauguier, and Brigitte Lelongt. The sam domain of anks6 has different interacting partners and mutations can induce different cystic phenotypes. Kidney international, 88 2:299-310, Aug 2015. URL: https://doi.org/10.1038/ki.2015.122, doi:10.1038/ki.2015.122. This article has 31 citations and is from a highest quality peer-reviewed journal.

7. (clark2020invivocharacterisationa pages 34-38): E Clark. In vivo characterisation of anks3-a new candidate for ciliopathic disease. Unknown journal, 2020.

8. (rothe2018crystalstructureof pages 10-11): Benjamin Rothé, Catherine N. Leettola, Lucia Leal-Esteban, Duilio Cascio, Simon Fortier, Manuela Isenschmid, James U. Bowie, and Daniel B. Constam. Crystal structure of bicc1 sam polymer and mapping of interactions between the ciliopathy-associated proteins bicc1, anks3, and anks6. Structure, 26:209-224.e6, Feb 2018. URL: https://doi.org/10.1016/j.str.2017.12.002, doi:10.1016/j.str.2017.12.002. This article has 36 citations and is from a domain leading peer-reviewed journal.

9. (rothe2023bicc1ribonucleoproteincomplexes pages 1-2): Benjamin Rothé, Yayoi Ikawa, Zhidian Zhang, Takanobu A. Katoh, Eriko Kajikawa, Katsura Minegishi, Sai Xiaorei, Simon Fortier, Matteo Dal Peraro, Hiroshi Hamada, and Daniel B. Constam. Bicc1 ribonucleoprotein complexes specifying organ laterality are licensed by anks6-induced structural remodeling of associated anks3. PLOS Biology, 21:e3002302, Sep 2023. URL: https://doi.org/10.1371/journal.pbio.3002302, doi:10.1371/journal.pbio.3002302. This article has 8 citations and is from a highest quality peer-reviewed journal.

10. (mahuzier2024theanks3bicc1protein pages 20-24): Alexia Mahuzier, Gweltas Odye, Valentina Grampa, Albane Bizet, Amandine Viau, Rebecca Ryan, Manon Mehraz, Thierry Blisnick, Euan Clark, Charline Henry, Rémi Piedagnel, Flora Silbermann, Gaelle Hayot, Line De grande, Agathe Kahn, Jean-Marc Plaza, Pauline Krug, Bertrand Knebelmann, Florian Muller, Philippe Bastin, Andreas W. Sailer, Pierre Saint-Mezard, Cécile Jeanpierre, Sigrid Hoffmann, Alexandre Benmerah, Brigitte Lelongt, Marion Delous, and Sophie Saunier. The anks3/bicc1 protein complex is a master post-transcriptional regulator of nphp1 ciliopathy-gene transcripts. bioRxiv, Apr 2024. URL: https://doi.org/10.1101/2024.04.18.588747, doi:10.1101/2024.04.18.588747. This article has 4 citations.

11. (mahuzier2024theanks3bicc1protein pages 1-5): Alexia Mahuzier, Gweltas Odye, Valentina Grampa, Albane Bizet, Amandine Viau, Rebecca Ryan, Manon Mehraz, Thierry Blisnick, Euan Clark, Charline Henry, Rémi Piedagnel, Flora Silbermann, Gaelle Hayot, Line De grande, Agathe Kahn, Jean-Marc Plaza, Pauline Krug, Bertrand Knebelmann, Florian Muller, Philippe Bastin, Andreas W. Sailer, Pierre Saint-Mezard, Cécile Jeanpierre, Sigrid Hoffmann, Alexandre Benmerah, Brigitte Lelongt, Marion Delous, and Sophie Saunier. The anks3/bicc1 protein complex is a master post-transcriptional regulator of nphp1 ciliopathy-gene transcripts. bioRxiv, Apr 2024. URL: https://doi.org/10.1101/2024.04.18.588747, doi:10.1101/2024.04.18.588747. This article has 4 citations.

12. (kofotolios2024thehansprdrat pages 7-8): Ioannis Kofotolios, Michael J. Bonios, Markos Adamopoulos, Iordanis Mourouzis, Gerasimos Filippatos, John N. Boletis, Smaragdi Marinaki, and Manolis Mavroidis. The han:sprd rat: a preclinical model of polycystic kidney disease. Biomedicines, 12:362, Feb 2024. URL: https://doi.org/10.3390/biomedicines12020362, doi:10.3390/biomedicines12020362. This article has 7 citations.

13. (nakajima2018theinvcompartment pages 1-2): Yoshiro Nakajima, Hiroshi Kiyonari, Yoshiko Mukumoto, and Takahiko Yokoyama. The inv compartment of renal cilia is an intraciliary signal-activating center to phosphorylate anks6. Kidney international, 93 5:1108-1117, May 2018. URL: https://doi.org/10.1016/j.kint.2017.11.016, doi:10.1016/j.kint.2017.11.016. This article has 26 citations and is from a highest quality peer-reviewed journal.

14. (bennett2020novelfibrillarstructure media 833c1b6b): Henrietta W. Bennett, Anna-Karin Gustavsson, Camille A. Bayas, Petar N. Petrov, Nancie Mooney, W. E. Moerner, and Peter K. Jackson. Novel fibrillar structure in the inversin compartment of primary cilia revealed by 3d single-molecule superresolution microscopy. Molecular Biology of the Cell, 31:619-639, Mar 2020. URL: https://doi.org/10.1091/mbc.e19-09-0499, doi:10.1091/mbc.e19-09-0499. This article has 60 citations and is from a domain leading peer-reviewed journal.

15. (bennett2020novelfibrillarstructure media af0b91fd): Henrietta W. Bennett, Anna-Karin Gustavsson, Camille A. Bayas, Petar N. Petrov, Nancie Mooney, W. E. Moerner, and Peter K. Jackson. Novel fibrillar structure in the inversin compartment of primary cilia revealed by 3d single-molecule superresolution microscopy. Molecular Biology of the Cell, 31:619-639, Mar 2020. URL: https://doi.org/10.1091/mbc.e19-09-0499, doi:10.1091/mbc.e19-09-0499. This article has 60 citations and is from a domain leading peer-reviewed journal.

16. (bennett2020novelfibrillarstructure media a7fab014): Henrietta W. Bennett, Anna-Karin Gustavsson, Camille A. Bayas, Petar N. Petrov, Nancie Mooney, W. E. Moerner, and Peter K. Jackson. Novel fibrillar structure in the inversin compartment of primary cilia revealed by 3d single-molecule superresolution microscopy. Molecular Biology of the Cell, 31:619-639, Mar 2020. URL: https://doi.org/10.1091/mbc.e19-09-0499, doi:10.1091/mbc.e19-09-0499. This article has 60 citations and is from a domain leading peer-reviewed journal.

17. (leettola2015asterilealpha pages 113-116): C Leettola. A sterile alpha motif domain network involved in kidney development. Unknown journal, 2015.

Citations

1. kofotolios2024thehansprdrat pages 7-8
2. nakajima2018theinvcompartment pages 1-2
3. bakey2015thesamdomain pages 1-2
4. clark2020invivocharacterisationa pages 34-38
5. bennett2020novelfibrillarstructure pages 1-4
6. rothe2018crystalstructureof pages 10-11
7. bennett2020novelfibrillarstructure pages 11-13
8. smith2019themechanisticfunctiona pages 56-59
9. leettola2015asterilealpha pages 113-116
10. https://doi.org/10.1371/journal.pbio.3002302
11. https://doi.org/10.1101/2024.04.18.588747
12. https://doi.org/10.3390/biomedicines12020362
13. https://doi.org/10.1038/ng.2681
14. https://doi.org/10.1038/ncomms7023
15. https://doi.org/10.1016/j.kint.2017.11.016
16. https://doi.org/10.1091/mbc.e19-09-0499
17. https://doi.org/10.1038/ki.2015.122
18. https://doi.org/10.1016/j.str.2017.12.002
19. https://doi.org/10.1093/hmg/ddaa197
20. https://doi.org/10.1091/mbc.e19-09-0499,
21. https://doi.org/10.1038/ng.2681,
22. https://doi.org/10.1038/ncomms7023,
23. https://doi.org/10.1038/ki.2015.122,
24. https://doi.org/10.1016/j.str.2017.12.002,
25. https://doi.org/10.1371/journal.pbio.3002302,
26. https://doi.org/10.1101/2024.04.18.588747,
27. https://doi.org/10.3390/biomedicines12020362,
28. https://doi.org/10.1016/j.kint.2017.11.016,

ANKS6 (SamCystin) – Function, Signaling, and Clinical Significance

Introduction and Key Features

ANKS6 (ankyrin repeat and SAM domain-containing protein 6, also known as SAMD6, ANKRD14, or SamCystin) is a human protein characterized by multiple ankyrin repeats and a C-terminal sterile alpha motif (SAM) domain (bmcstructbiol.biomedcentral.com) (www.nature.com). Ankyrin repeats typically mediate protein–protein interactions, suggesting ANKS6 acts as a scaffold or adaptor in cells. The SAM domain is a polymerizing protein–protein interaction module, and structural studies show ANKS6’s SAM domain binds to the SAM domain of its paralog ANKS3 (bmcstructbiol.biomedcentral.com). In fact, ANKS3 can self-polymerize via its SAM domain, and ANKS6 attaches to the end of the ANKS3 polymer, forming a multi-protein complex (bmcstructbiol.biomedcentral.com). This domain arrangement (ankyrin repeats + SAM) places ANKS6 in a family of intracellular adapter proteins involved in signaling complexes. UniProt Q68DC2 confirms ANKS6’s identity in Homo sapiens and its domain architecture, ensuring we focus on the correct human gene product (NPHP16) and not a similarly named gene in another species.

Localization and Biological Function

ANKS6 localizes predominantly to the primary cilium of cells – a microscopic antenna-like organelle critical for sensing extracellular signals (pubmed.ncbi.nlm.nih.gov). In kidney epithelial cells, ANKS6 is enriched in the proximal segment of the cilium (sometimes referred to as the “inversin compartment”) (pubmed.ncbi.nlm.nih.gov). Notably, in the kidney’s proximal tubules, native Anks6 (Samcystin) was detected at the apical brush border region (pmc.ncbi.nlm.nih.gov), consistent with ciliary or periciliary localization. Through its ankyrin-repeat domain, ANKS6 binds other ciliary proteins, and it serves as a molecular hub linking several nephronophthisis (NPHP) proteins (www.nature.com). Specifically, ANKS6 directly connects to the kinase NEK8 (NPHP9) and the proteins INVS (Inversin, NPHP2) and NPHP3 within the ciliary apparatus (www.nature.com). This ANKS6-centered complex is crucial for renal tubular development: knockdown of Anks6 in model organisms (zebrafish and Xenopus) causes pronephric cysts and developmental defects (www.nature.com). These findings indicate that ANKS6 is essential for normal kidney morphogenesis and function, likely by organizing protein signaling in primary cilia, the key organelle for coordinating developmental signals in kidney tubule cells (www.nature.com).

Beyond the kidney, ANKS6’s ciliary role extends to other developmental systems. Mutations in ANKS6 can cause situs inversus (left-right body axis reversal) (www.nature.com), implying a role in embryonic node cilia that establish left-right asymmetry. Indeed, ANKS6’s partner protein inversin (NPHP2) is a known regulator of left-right patterning and Wnt signaling. ANKS6 lies upstream of inversin in the ciliary signaling hierarchy (pmc.ncbi.nlm.nih.gov). By tethering inversin and other factors in the cilium, ANKS6 helps control the Wnt/β-catenin pathway and planar cell polarity during development (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Consistent with this, loss of ANKS6 function leads to aberrant Wnt signaling: patient kidney biopsies and Anks6-mutant rat kidneys show abnormally high levels of active β-catenin in renal tubules (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This indicates overactivation of canonical Wnt signaling, which is known to drive cyst formation when not properly balanced (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Thus, under normal conditions ANKS6 (via inversin) likely acts as a brake on Wnt/β-catenin signaling in the kidney, helping maintain the delicate signaling balance required to prevent uncontrolled cell proliferation and cystogenesis (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Signaling Pathways and Complex Interactions

ANKS6 is emerging as a critical integrator of ciliary signaling pathways. One of its key functions is to facilitate the proper localization and activation of the kinase NEK8 within the cilium. Recent studies indicate that ANKS6 physically transports NEK8 from the cytoplasm into the cilium, where NEK8 can be phosphorylated and activated in the presence of inversin and NPHP3 (pmc.ncbi.nlm.nih.gov). In this capacity, ANKS6 acts as both a substrate and an activator of NEK8’s kinase activity (pmc.ncbi.nlm.nih.gov). Activated NEK8, in turn, is known to participate in the Hippo signaling pathway and other growth-regulatory cascades. Notably, NEK8 and other NPHP proteins (e.g. NPHP4, NPHP3) promote phosphorylation of the transcriptional co-activator YAP/TAZ, sequestering YAP at the cilium and preventing excessive cell proliferation (academic.oup.com). ANKS6 is now recognized to modulate the Hippo–YAP pathway through this mechanism (academic.oup.com). In ANKS6-deficient patient cells, researchers observed a mislocalization of YAP: phosphorylated YAP that normally decorates the ciliary axoneme was instead confined to the ciliary base, and total YAP became overactive and accumulated in nuclei (academic.oup.com) (academic.oup.com). Concordantly, YAP target genes (such as CTGF, CYR61, JAG1, and TEAD4) were significantly upregulated in ANKS6-mutant cells (academic.oup.com). This YAP dysregulation provides a mechanistic link between ciliary dysfunction and the pro-proliferative transcriptional changes seen in cystic kidney disease (academic.oup.com) (academic.oup.com). In short, ANKS6 helps maintain proper Hippo/YAP signaling by anchoring relevant kinases and perhaps sequestering phosphorylated YAP in cilia, thereby keeping cell growth in check.

ANKS6 also interacts with ANKS3 (a related ankyrin/SAM protein) and the RNA-binding protein BICC1 to influence cyclic AMP (cAMP)–dependent signaling in kidney tubules (pmc.ncbi.nlm.nih.gov). The cAMP pathway (stimulated by vasopressin via V2 receptors) is a known driver of cyst growth when overactive, due to increased epithelial cell proliferation and fluid secretion. In Anks6-mutant (Cy/+) rats, gene expression profiling revealed dysregulation of water channel aquaporins (AQP2/3/4) and other markers of vasopressin/cAMP signaling, suggesting that an ANKS6–ANKS3–BICC1 network normally restrains this pathway (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Evidence from Bicc1-knockout mice likewise indicates these proteins function together to modulate cAMP levels in renal epithelial cells (pmc.ncbi.nlm.nih.gov). Thus, ANKS6 sits at a crossroads of multiple signaling routes – Wnt/β-catenin, Hippo-YAP, and cAMP/PKD-related pathways – all of which must be finely tuned for normal kidney structure. Interestingly, there are hints that ANKS6 may interface with the polycystin-1/2 signaling pathway as well. Cystic kidneys from Anks6-mutant rats show alterations in MAPK/ERK, AKT/mTOR, and RXR pathways similar to those seen with polycystin mutations (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Researchers have speculated that the SAM domain of ANKS6 might directly influence polycystin-1 signaling complexes, linking ANKS6 to the canonical autosomal dominant PKD pathway (pmc.ncbi.nlm.nih.gov). While the precise molecular events are still being uncovered, it is clear that ANKS6 serves as a critical scaffold in the cilium that coordinates multiple signaling proteins, ensuring proper downstream developmental signals and preventing pathogenic cascades.

Clinical Significance and Disease Associations

Mutations in ANKS6 cause a human ciliopathy known as nephronophthisis 16 (NPHP16), a form of recessive cystic kidney disease (pubmed.ncbi.nlm.nih.gov). Nephronophthisis (NPHP) is characterized by fibrosis and cysts at the cortico-medullary junction of the kidneys, leading to chronic kidney failure typically in childhood or adolescence. Although NPHP is genetically heterogeneous (with over 20 genes identified), ANKS6 mutations represent a rare cause. According to GeneReviews (2023 update), ANKS6 accounts for <1% of NPHP-related ciliopathy cases (www.ncbi.nlm.nih.gov). Despite its rarity, ANKS6-associated disease is distinctive for often having multi-organ involvement. Patients with biallelic ANKS6 mutations (usually truncating or missense variants in conserved regions) develop cystic kidney disease that can range from infantile-onset to adult-onset in severity (www.ncbi.nlm.nih.gov). Classically, childhood-onset end-stage renal disease was reported in several families, along with congenital heart defects, liver fibrosis, and situs inversus (reversal of left-right organ positioning) (www.nature.com). These extrarenal manifestations – which parallel those seen with mutations in INVS/NPHP2 and NEK8 – reflect the systemic role of ANKS6 in ciliary developmental processes. Notably, unlike many other NPHP genes, ANKS6 mutations have not been strongly linked to retinal degeneration (retinitis pigmentosa) (www.ncbi.nlm.nih.gov), suggesting a degree of tissue selectivity in where ANKS6 is most critical (kidney, liver, heart, brain laterality, etc.).

Discovery and case studies: ANKS6’s link to human disease was first demonstrated in 2013 when six unrelated NPHP families were found to carry mutations in ANKS6 (www.nature.com). These individuals presented in childhood with renal failure and a constellation of anomalies (e.g. cardiopathy, biliary fibrosis, situs inversus), firmly establishing ANKS6 as a ciliopathy gene (www.nature.com). In 2014, Taskiran et al. reported a Turkish kindred with ANKS6 mutations causing juvenile nephronophthisis and end-stage kidney disease by the late teens (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Kidney biopsies from that patient showed dilated tubules with strong β-catenin staining, implicating hyperactive Wnt signaling in the disease mechanism (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Meanwhile, in animal models, the Han:SPRD Cy rat – a longstanding model of polycystic kidney disease – was unexpectedly found to harbor a mutation in the Anks6 gene (a point substitution R823W in the SAM domain) (bmcstructbiol.biomedcentral.com). This single mutation in Anks6 (“Cy” allele) is sufficient to cause autosomal dominant polycystic kidney disease in rats, with cystic enlargement of kidneys resembling human PKD (bmcstructbiol.biomedcentral.com) (pmc.ncbi.nlm.nih.gov). The Cy Rat (Anks6^R823W) has been used extensively as a preclinical model for testing PKD therapies and studying cystogenesis (bmcstructbiol.biomedcentral.com). Analysis of this model showed that the mutant Samcystin protein is mislocalized in cyst-lining cells and likely exerts a dominant-negative effect on the ciliary signaling complex (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Together, human and animal studies underscore that ANKS6 loss-of-function (in patients) or domain mutation (in the rat) disrupts ciliary signal transduction, leading to renal cyst formation and fibrosis.

Latest Research and Developments (2020–2024)

Recent insights (2020–2022) have shed light on how ANKS6 mutations impact downstream pathways. In a 2022 study of two adult sisters with atypically late-onset chronic kidney disease (mid-adulthood) caused by biallelic ANKS6 mutations, Schwarz et al. discovered a link to the Hippo/YAP pathway (academic.oup.com) (academic.oup.com). Patient-derived cells showed excess nuclear YAP and altered YAP phosphorylation at the cilium, resulting in increased expression of YAP-dependent genes that drive proliferation (academic.oup.com). This finding reveals that ANKS6 is required for proper Hippo signaling and that its disruption can lead to unchecked cell growth even in slowly progressive disease cases. Intriguingly, the same study noted alterations in canonical Wnt signaling in ANKS6-mutant cells (including elevated active β-catenin and GSK3β changes) (academic.oup.com), reinforcing that ANKS6 normally helps balance Wnt activity as well. These mechanistic advances confirm a unifying concept: cystic kidney diseases caused by ciliary gene defects (like ANKS6, NEK8, NPHP2/3) may all promote cyst growth through a common nexus of Wnt and YAP/TAZ signaling dysregulation (academic.oup.com) (academic.oup.com).

Diagnostics and clinical applications (2023–2024): As ANKS6’s role became recognized, it has been added to gene testing panels for inherited kidney diseases. Genetic diagnosis is particularly valuable in atypical or early presentations. A 2024 report described three consanguineous families from the Middle East in which fetuses or neonates presented with enlarged, echogenic polycystic kidneys (pubmed.ncbi.nlm.nih.gov). Through whole-exome sequencing, those cases were solved by identifying homozygous ANKS6 mutations (pubmed.ncbi.nlm.nih.gov). This expanded the clinical spectrum of ANKS6: it can cause perinatal massively polycystic kidneys (resembling severe ARPKD) in addition to the previously known juvenile or adult-onset presentations. These discoveries highlight the utility of prenatal genetic testing when ultrasound shows cystic kidney disease – in one family, an ANKS6 diagnosis was made antenatally, guiding early prognostic counseling (pubmed.ncbi.nlm.nih.gov). More broadly, recognizing ANKS6 mutations in patients with laterality defects or heart malformations can prompt screening for kidney issues, given the gene’s pleiotropic effects. There is no specific targeted therapy for ANKS6-associated NPHP yet, but management focuses on controlling cyst progression (e.g. blood pressure control, vasopressin V2 receptor antagonists to reduce cAMP if appropriate) and timely transplantation for kidney failure. On the research front, the Anks6^Cy/+ rat continues to be a valuable model – its use has illuminated how cAMP-modulating treatments (like vasopressin antagonists) might benefit cystic disease by counteracting the loss of ANKS6 function (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). As of 2024, ANKS6 stands out as a mechanistically informative gene in the ciliopathy field, and ongoing studies are probing its exact molecular interactions (e.g. with Polycystin-1, BICC1) and potential as a therapeutic target in cystic organ diseases.

Expert Perspectives and Conclusion

From an expert viewpoint, ANKS6 (SAMD6/Samcystin) exemplifies how primary cilia act as signaling hubs in organ development and disease. Friedhelm Hildebrandt and colleagues, who first pinpointed ANKS6’s role, described it as a “central component” of a ciliary protein module that explains why mutations in different module members (ANKS6, NEK8, INVS, NPHP3) cause strikingly similar syndromes (www.nature.com). GeneReviews (2023) emphasizes the multi-system nature of ANKS6-related disease, noting that patients can have neurological involvement, congenital heart disease, biliary fibrosis, and situs inversus in addition to kidney failure (www.ncbi.nlm.nih.gov). These clinical features mirror the protein’s involvement in fundamental developmental pathways across organ systems. Researchers also note that while ANKS6 is structurally distinct from the polycystin proteins (PKD1/PKD2), it likely converges functionally on common cystogenic pathways. For example, an analysis of the Cy/+ rat model suggested that the ANKS6 mutation triggers changes in B-Raf/MEK/ERK and mTOR signaling, akin to those seen in polycystic kidney disease (pmc.ncbi.nlm.nih.gov). This has led to the intriguing suggestion that Samcystin’s SAM domain might directly partake in polycystin-1 related signaling (pmc.ncbi.nlm.nih.gov), hinting at a broader role in the kidney’s mechanosensory machinery. While many details remain to be uncovered, the current understanding presents ANKS6 as a ciliary adaptor protein critical for routing signals (Wnt, Hippo/YAP, cAMP) from the cilium to the cell nucleus. Disruption of ANKS6 destabilizes this signaling nexus – leading to misregulation of cell polarity, proliferation, and differentiation – and ultimately results in cystic organ pathologies. Ongoing research in 2023–2024 continues to refine this picture, with the hope that deeper insight into ANKS6’s function will open avenues for targeted interventions in ciliopathies and cystic kidney diseases (academic.oup.com) (pubmed.ncbi.nlm.nih.gov). In summary, ANKS6 is a keystone in the ciliary signaling network, and its study is illuminating the delicate biochemical circuits that maintain renal architecture and organismal left-right patterning. Future studies and therapeutic developments will likely benefit from the rich mechanistic knowledge base that ANKS6 research has established in the past decade.

References: (Select recent and authoritative sources)
- Hoff et al., Nature Genetics (2013) – Identified ANKS6 as NPHP16; links ANKS6 with NEK8-INVS-NPHP3 complex (www.nature.com).
- Taskiran et al., J. Am. Soc. Nephrol. (2014) – Confirmed ANKS6 mutations cause cystic kidney disease; showed Wnt/β-catenin activation in ANKS6-deficient tissue (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).
- Leettola et al., BMC Struct. Biol. (2014) – Characterized ANKS6 SAM domain, interaction with ANKS3; structural impact of R823W mutation (bmcstructbiol.biomedcentral.com) (bmcstructbiol.biomedcentral.com).
- Schwarz et al., Hum. Mol. Genet. (2022) – Reported adult-onset ANKS6 ciliopathy; revealed YAP misregulation and Hippo pathway involvement (academic.oup.com) (academic.oup.com).
- Stokman et al., GeneReviews (updated 2023) – Overview of nephronophthisis-related ciliopathies; lists ANKS6 (NPHP16) clinical spectrum (www.ncbi.nlm.nih.gov).
- Kofotolios et al., Biomedicines (2024) – Review of Han:SPRD (Cy) rat PKD model; discusses Samcystin (Anks6) role in cystogenesis and cAMP signaling (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).
- Al-Hamed et al., Genes (2024) – Case report series of antenatal polycystic kidneys caused by ANKS6 mutations; underscores importance of prenatal genetic diagnosis (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov).

Citations

1. AnnotationURLCitation(end_index=547, start_index=341, title='Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3 | BMC Structural Biology | Full Text', type='url_citation', url='https://bmcstructbiol.biomedcentral.com/articles/10.1186/1472-6807-14-17#:~:text=Autosomal%20dominant%20polycystic%20kidney%20disease,with%20ankyrin%20repeats%20at%20the')
2. AnnotationURLCitation(end_index=707, start_index=548, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng.2681#:~:text=ANKS6%20mutations%20affected%20by%20nephronophthisis%2C,in%20ANKS6%2C%20NEK8%2C%20INVS%20or')
3. AnnotationURLCitation(end_index=1156, start_index=991, title='Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3 | BMC Structural Biology | Full Text', type='url_citation', url='https://bmcstructbiol.biomedcentral.com/articles/10.1186/1472-6807-14-17#:~:text=The%20SAM%20domain%20of%20ANKS3,SAM%20is%20lost')
4. AnnotationURLCitation(end_index=1462, start_index=1297, title='Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3 | BMC Structural Biology | Full Text', type='url_citation', url='https://bmcstructbiol.biomedcentral.com/articles/10.1186/1472-6807-14-17#:~:text=The%20SAM%20domain%20of%20ANKS3,SAM%20is%20lost')
5. AnnotationURLCitation(end_index=2152, start_index=1998, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/23793029/#:~:text=renal%20failure%20in%20childhood%20or,in%20a%20phenotype%20that%20resembles')
6. AnnotationURLCitation(end_index=2446, start_index=2292, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/23793029/#:~:text=renal%20failure%20in%20childhood%20or,in%20a%20phenotype%20that%20resembles')
7. AnnotationURLCitation(end_index=2751, start_index=2563, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=Samcystin%20expression%20is%20consistent%20with,%E2%80%9CR823W%E2%80%9D%20in%20the%20samcystin%20domain')
8. AnnotationURLCitation(end_index=3122, start_index=2963, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng.2681#:~:text=ANKS6%20mutations%20affected%20by%20nephronophthisis%2C,in%20ANKS6%2C%20NEK8%2C%20INVS%20or')
9. AnnotationURLCitation(end_index=3439, start_index=3280, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng.2681#:~:text=ANKS6%20mutations%20affected%20by%20nephronophthisis%2C,in%20ANKS6%2C%20NEK8%2C%20INVS%20or')
10. AnnotationURLCitation(end_index=3784, start_index=3625, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng.2681#:~:text=ANKS6%20mutations%20affected%20by%20nephronophthisis%2C,in%20ANKS6%2C%20NEK8%2C%20INVS%20or')
11. AnnotationURLCitation(end_index=4184, start_index=4025, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng.2681#:~:text=ANKS6%20mutations%20affected%20by%20nephronophthisis%2C,in%20ANKS6%2C%20NEK8%2C%20INVS%20or')
12. AnnotationURLCitation(end_index=4506, start_index=4347, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng.2681#:~:text=ANKS6%20mutations%20affected%20by%20nephronophthisis%2C,in%20ANKS6%2C%20NEK8%2C%20INVS%20or')
13. AnnotationURLCitation(end_index=4915, start_index=4770, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=reported%20that%20ANKS6%20affects%20the,old%20Cy%2F%2B%20rats')
14. AnnotationURLCitation(end_index=5211, start_index=5066, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=reported%20that%20ANKS6%20affects%20the,old%20Cy%2F%2B%20rats')
15. AnnotationURLCitation(end_index=5389, start_index=5212, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=diseases.%5E%7B24%E2%80%9326%7D%20The%20canonical%20%CE%B2,Wnt%20pathway%20lead%20to%20cystic')
16. AnnotationURLCitation(end_index=5751, start_index=5591, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=with%20specific%20antibodies%20against%20total,or%20only%20stain%20for%20the')
17. AnnotationURLCitation(end_index=5923, start_index=5752, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=Semiquantitative%20evaluation%20showed%20that%20tubular,catenin%20were%20increased%20in')
18. AnnotationURLCitation(end_index=6230, start_index=6053, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=diseases.%5E%7B24%E2%80%9326%7D%20The%20canonical%20%CE%B2,Wnt%20pathway%20lead%20to%20cystic')
19. AnnotationURLCitation(end_index=6402, start_index=6231, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=Semiquantitative%20evaluation%20showed%20that%20tubular,catenin%20were%20increased%20in')
20. AnnotationURLCitation(end_index=6814, start_index=6637, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=diseases.%5E%7B24%E2%80%9326%7D%20The%20canonical%20%CE%B2,Wnt%20pathway%20lead%20to%20cystic')
21. AnnotationURLCitation(end_index=6986, start_index=6815, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=Semiquantitative%20evaluation%20showed%20that%20tubular,catenin%20were%20increased%20in')
22. AnnotationURLCitation(end_index=7574, start_index=7426, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=regulating%20polycystic%20kidney%20function,generating%20center')
23. AnnotationURLCitation(end_index=7818, start_index=7670, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=regulating%20polycystic%20kidney%20function,generating%20center')
24. AnnotationURLCitation(end_index=8329, start_index=8144, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=match%20at%20L337%20shown%20that,YAP%20imbalances%2C%20resulting%20in')
25. AnnotationURLCitation(end_index=8617, start_index=8416, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=remodeling%20defects%20and%20periportal%20fibrosis,transcriptional%20activity%20%2814')
26. AnnotationURLCitation(end_index=9078, start_index=8863, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=Immunofluorescence%20staining%20revealed%20that%20phosphorylated,cilia%20of%20the%20control%20cells')
27. AnnotationURLCitation(end_index=9246, start_index=9079, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=match%20at%20L543%20mutant%20fibroblasts%2C,Nuclear')
28. AnnotationURLCitation(end_index=9547, start_index=9383, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=Material%2C%20Fig,derived%20cells%20%28Fig.%203C')
29. AnnotationURLCitation(end_index=9914, start_index=9712, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=match%20at%20L351%20dysregulation%20of,pathway%20through%20modulating%20YAP%20activity')
30. AnnotationURLCitation(end_index=10079, start_index=9915, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=Material%2C%20Fig,derived%20cells%20%28Fig.%203C')
31. AnnotationURLCitation(end_index=10584, start_index=10441, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=Additionally%2C%20evidence%20of%20BICC1,38%20%2C%2059%2C68')
32. AnnotationURLCitation(end_index=11176, start_index=11015, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=insight%20sheds%20light%20on%20the,in%20response%20to%20experimental%20anks3')
33. AnnotationURLCitation(end_index=11320, start_index=11177, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=Additionally%2C%20evidence%20of%20BICC1,38%20%2C%2059%2C68')
34. AnnotationURLCitation(end_index=11601, start_index=11458, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=Additionally%2C%20evidence%20of%20BICC1,38%20%2C%2059%2C68')
35. AnnotationURLCitation(end_index=12203, start_index=12046, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=cilia%2C%20where%20it%20is%20phosphorylated,47%20%2C%2082%2C63%5D.%20The')
36. AnnotationURLCitation(end_index=12362, start_index=12204, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=idea%20that%20ANKS6%20interacts%20with,Cy%2F%2B%29%20rats%2C%20suggesting')
37. AnnotationURLCitation(end_index=12695, start_index=12542, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=common%20denominator%20in%20the%20pathophysiology,38%20%2C%2059%2C68')
38. AnnotationURLCitation(end_index=13293, start_index=13147, title='ANKS6 Variants Underlie Polycystic Kidneys in Prenatal and Neonatal Cases - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39596574#:~:text=Background%3A%20Nephronophthisis%20,the%20early%20stages%20of%20life')
39. AnnotationURLCitation(end_index=13836, start_index=13697, title='Nephronophthisis-Related Ciliopathies - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/NBK368475/#:~:text=Less%20common%20genes%20ADAMTS9%20,Liver%20dz%2C%20deafness')
40. AnnotationURLCitation(end_index=14256, start_index=14140, title='Nephronophthisis-Related Ciliopathies - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/NBK368475/#:~:text=Less%20common%20genes%20ADAMTS9%20,6')
41. AnnotationURLCitation(end_index=14627, start_index=14468, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng.2681#:~:text=ANKS6%20mutations%20affected%20by%20nephronophthisis%2C,in%20ANKS6%2C%20NEK8%2C%20INVS%20or')
42. AnnotationURLCitation(end_index=15048, start_index=14932, title='Nephronophthisis-Related Ciliopathies - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/NBK368475/#:~:text=Less%20common%20genes%20ADAMTS9%20,6')
43. AnnotationURLCitation(end_index=15497, start_index=15338, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng.2681#:~:text=ANKS6%20mutations%20affected%20by%20nephronophthisis%2C,in%20ANKS6%2C%20NEK8%2C%20INVS%20or')
44. AnnotationURLCitation(end_index=15856, start_index=15697, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng.2681#:~:text=ANKS6%20mutations%20affected%20by%20nephronophthisis%2C,in%20ANKS6%2C%20NEK8%2C%20INVS%20or')
45. AnnotationURLCitation(end_index=16159, start_index=16014, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=reported%20that%20ANKS6%20affects%20the,old%20Cy%2F%2B%20rats')
46. AnnotationURLCitation(end_index=16331, start_index=16160, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=Semiquantitative%20evaluation%20showed%20that%20tubular,catenin%20were%20increased%20in')
47. AnnotationURLCitation(end_index=16641, start_index=16489, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=Immunohistochemistry%20with%20anti%E2%80%93%CE%B2,bottom%29%20probed')
48. AnnotationURLCitation(end_index=16813, start_index=16642, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=Semiquantitative%20evaluation%20showed%20that%20tubular,catenin%20were%20increased%20in')
49. AnnotationURLCitation(end_index=17239, start_index=17033, title='Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3 | BMC Structural Biology | Full Text', type='url_citation', url='https://bmcstructbiol.biomedcentral.com/articles/10.1186/1472-6807-14-17#:~:text=Autosomal%20dominant%20polycystic%20kidney%20disease,with%20ankyrin%20repeats%20at%20the')
50. AnnotationURLCitation(end_index=17626, start_index=17420, title='Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3 | BMC Structural Biology | Full Text', type='url_citation', url='https://bmcstructbiol.biomedcentral.com/articles/10.1186/1472-6807-14-17#:~:text=Autosomal%20dominant%20polycystic%20kidney%20disease,with%20ankyrin%20repeats%20at%20the')
51. AnnotationURLCitation(end_index=17789, start_index=17627, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=mislocalization%20of%20the%20protein,not%20fully%20understood%2C%20a%20recent')
52. AnnotationURLCitation(end_index=18107, start_index=17923, title='Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3 | BMC Structural Biology | Full Text', type='url_citation', url='https://bmcstructbiol.biomedcentral.com/articles/10.1186/1472-6807-14-17#:~:text=causal%20of%20disease%2C%20has%20been,domain%20of%20ANKS3%20as%20a')
53. AnnotationURLCitation(end_index=18457, start_index=18288, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=specificity%20for%20its%20localization%20to,and%20a%20dominant%20negative%20reaction')
54. AnnotationURLCitation(end_index=18616, start_index=18458, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=precise%20role%20of%20ANKS6%20in,an%20important%20regulator%20in%20kidney')
55. AnnotationURLCitation(end_index=19385, start_index=19184, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=remodeling%20defects%20and%20periportal%20fibrosis,transcriptional%20activity%20%2814')
56. AnnotationURLCitation(end_index=19550, start_index=19386, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=Material%2C%20Fig,derived%20cells%20%28Fig.%203C')
57. AnnotationURLCitation(end_index=19893, start_index=19729, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=Material%2C%20Fig,derived%20cells%20%28Fig.%203C')
58. AnnotationURLCitation(end_index=20356, start_index=20222, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=nuclear%20yes,Upon')
59. AnnotationURLCitation(end_index=20846, start_index=20661, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=match%20at%20L337%20shown%20that,YAP%20imbalances%2C%20resulting%20in')
60. AnnotationURLCitation(end_index=21049, start_index=20847, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=match%20at%20L351%20dysregulation%20of,pathway%20through%20modulating%20YAP%20activity')
61. AnnotationURLCitation(end_index=21601, start_index=21455, title='ANKS6 Variants Underlie Polycystic Kidneys in Prenatal and Neonatal Cases - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39596574#:~:text=Background%3A%20Nephronophthisis%20,the%20early%20stages%20of%20life')
62. AnnotationURLCitation(end_index=21883, start_index=21705, title='ANKS6 Variants Underlie Polycystic Kidneys in Prenatal and Neonatal Cases - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39596574#:~:text=Conclusions%3A%20We%20identified%20homozygous%20ANKS6,echogenic%20kidneys%20in%20prenatal%20settings')
63. AnnotationURLCitation(end_index=22476, start_index=22298, title='ANKS6 Variants Underlie Polycystic Kidneys in Prenatal and Neonatal Cases - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39596574#:~:text=Conclusions%3A%20We%20identified%20homozygous%20ANKS6,echogenic%20kidneys%20in%20prenatal%20settings')
64. AnnotationURLCitation(end_index=23308, start_index=23165, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=Additionally%2C%20evidence%20of%20BICC1,38%20%2C%2059%2C68')
65. AnnotationURLCitation(end_index=23462, start_index=23309, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=common%20denominator%20in%20the%20pathophysiology,38%20%2C%2059%2C68')
66. AnnotationURLCitation(end_index=24302, start_index=24159, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng.2681#:~:text=hydroxylates%20ANKS6%20and%20INVS%20and,in%20ANKS6%2C%20NEK8%2C%20INVS%20or')
67. AnnotationURLCitation(end_index=24676, start_index=24537, title='Nephronophthisis-Related Ciliopathies - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/NBK368475/#:~:text=Less%20common%20genes%20ADAMTS9%20,Liver%20dz%2C%20deafness')
68. AnnotationURLCitation(end_index=25314, start_index=25156, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=idea%20that%20ANKS6%20interacts%20with,Cy%2F%2B%29%20rats%2C%20suggesting')
69. AnnotationURLCitation(end_index=25600, start_index=25447, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=common%20denominator%20in%20the%20pathophysiology,38%20%2C%2059%2C68')
70. AnnotationURLCitation(end_index=26474, start_index=26272, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=match%20at%20L351%20dysregulation%20of,pathway%20through%20modulating%20YAP%20activity')
71. AnnotationURLCitation(end_index=26653, start_index=26475, title='ANKS6 Variants Underlie Polycystic Kidneys in Prenatal and Neonatal Cases - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39596574#:~:text=Conclusions%3A%20We%20identified%20homozygous%20ANKS6,echogenic%20kidneys%20in%20prenatal%20settings')
72. AnnotationURLCitation(end_index=27351, start_index=27192, title='ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng.2681#:~:text=ANKS6%20mutations%20affected%20by%20nephronophthisis%2C,in%20ANKS6%2C%20NEK8%2C%20INVS%20or')
73. AnnotationURLCitation(end_index=27681, start_index=27521, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=with%20specific%20antibodies%20against%20total,or%20only%20stain%20for%20the')
74. AnnotationURLCitation(end_index=27853, start_index=27682, title='Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4116054/#:~:text=Semiquantitative%20evaluation%20showed%20that%20tubular,catenin%20were%20increased%20in')
75. AnnotationURLCitation(end_index=28205, start_index=27999, title='Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3 | BMC Structural Biology | Full Text', type='url_citation', url='https://bmcstructbiol.biomedcentral.com/articles/10.1186/1472-6807-14-17#:~:text=Autosomal%20dominant%20polycystic%20kidney%20disease,with%20ankyrin%20repeats%20at%20the')
76. AnnotationURLCitation(end_index=28371, start_index=28206, title='Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3 | BMC Structural Biology | Full Text', type='url_citation', url='https://bmcstructbiol.biomedcentral.com/articles/10.1186/1472-6807-14-17#:~:text=The%20SAM%20domain%20of%20ANKS3,SAM%20is%20lost')
77. AnnotationURLCitation(end_index=28720, start_index=28519, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=remodeling%20defects%20and%20periportal%20fibrosis,transcriptional%20activity%20%2814')
78. AnnotationURLCitation(end_index=28885, start_index=28721, title='Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation | Human Molecular Genetics | Oxford Academic', type='url_citation', url='https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddab322/6420895#:~:text=Material%2C%20Fig,derived%20cells%20%28Fig.%203C')
79. AnnotationURLCitation(end_index=29169, start_index=29030, title='Nephronophthisis-Related Ciliopathies - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/NBK368475/#:~:text=Less%20common%20genes%20ADAMTS9%20,Liver%20dz%2C%20deafness')
80. AnnotationURLCitation(end_index=29470, start_index=29327, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=Additionally%2C%20evidence%20of%20BICC1,38%20%2C%2059%2C68')
81. AnnotationURLCitation(end_index=29619, start_index=29471, title='The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10887417/#:~:text=regulating%20polycystic%20kidney%20function,generating%20center')
82. AnnotationURLCitation(end_index=29938, start_index=29792, title='ANKS6 Variants Underlie Polycystic Kidneys in Prenatal and Neonatal Cases - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39596574#:~:text=Background%3A%20Nephronophthisis%20,the%20early%20stages%20of%20life')
83. AnnotationURLCitation(end_index=30117, start_index=29939, title='ANKS6 Variants Underlie Polycystic Kidneys in Prenatal and Neonatal Cases - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39596574#:~:text=Conclusions%3A%20We%20identified%20homozygous%20ANKS6,echogenic%20kidneys%20in%20prenatal%20settings')