| 2025 |
BORCS5 encodes a subunit of the BORC complex required for kinesin-dependent anterograde (peripheral) movement of lysosomes; loss-of-function variants (protein-truncating) cause perinuclear lysosomal clustering and impaired lysosomal axonal trafficking in iPSC-derived forebrain neurons, whereas missense variants do not cause this trafficking defect. |
Patient-derived cell studies (iPSC-derived neurons), zebrafish Borcs5 KO, whole-exome sequencing, lysosomal localization imaging |
The Journal of clinical investigation |
High |
42012897
|
| 2025 |
BORCS5 is required for lysosomal function beyond anterograde transport: both loss-of-function and missense BORCS5 variants are associated with reduced total lysosomal proteolysis, reduced activity of lysosomal hydrolases glucocerebrosidase and cathepsin B, and accumulation of multilamellar bodies, revealing a role for BORCS5 in regulating lysosomal hydrolytic function. |
Lysosomal hydrolase activity assays (glucocerebrosidase, cathepsin B), proteolysis assays, electron microscopy of multilamellar bodies in patient-derived cells |
The Journal of clinical investigation |
High |
40385417 42012897
|
| 2025 |
Loss-of-function (protein-truncating) BORCS5 variants, but not missense variants, result in lower BORCS5 protein expression and impaired BORC complex assembly, demonstrating that BORCS5 is structurally essential for BORC integrity. |
Western blot (protein expression), co-immunoprecipitation or co-fractionation for BORC assembly assessment in patient-derived cells |
medRxiv |
Medium |
40385417 42012897
|
| 2026 |
The octameric BORC complex is formed by two intertwined tetramers; cross-linking mass spectrometry of endogenous human BORC validates this architecture, and specific interfacial residues are essential for complex integrity and lysosomal transport. BORCS5 contains a pH-sensitive histidine residue proposed to regulate BORC formation and function. |
Cross-linking mass spectrometry of endogenous complexes, C. elegans BORC structure determination, interfacial residue mutagenesis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
41557793
|
| 2023 |
BORCS5 (as part of BORC components BORCS5-8) promotes peripheral lysosome positioning via Kinesin-1; depletion of BORCS5-8 or Kinesin-1 (but not Kinesin-3) in macrophages reverts autophagy evasion by M. tuberculosis Beijing strain, increases lysosomal delivery to bacterial phagosomes, and causes augmented perinuclear lysosomal relocation. |
siRNA knockdown of BORCS5-8 and Kinesin-1/3 in macrophages, lysosomal delivery assays to phagosomes, lysosomal positioning imaging |
Scientific reports |
Medium |
36717601
|
| 2018 |
BORCS5 (LOH12CR1) knockdown in colorectal cancer cell lines promotes cell proliferation and accelerates G1/S cell cycle transition through downregulation of p16INK4a and p21WAF1/CIP1; ectopic overexpression produces the opposite effects, placing BORCS5 as a regulator of the G1/S checkpoint. |
siRNA knockdown and ectopic overexpression in colorectal cancer cell lines, cell cycle analysis (flow cytometry), colony formation assay, western blot for p16INK4a and p21WAF1/CIP1 |
Current molecular medicine |
Medium |
29879888
|
| 2019 |
The LMO3-BORCS5 fusion oncogene (disrupting BORCS5) increases proliferation, decreases apoptosis-related gene expression and treatment sensitivity, downregulates differentiation genes, and induces tumors in NIH-3T3 mouse fibroblasts in vivo, suggesting that disruption of intact BORCS5 contributes to oncogenesis. |
In vitro proliferation and apoptosis assays, gene expression profiling, in vivo tumor formation in NIH-3T3 cells |
Oncogene |
Medium |
31488873
|
| 2019 |
A BORCS5-ETV6 fusion gene identified in scirrhous-type gastric cancer cell line OCUM-9 possesses oncogenic activity; suppression of its message partially inhibits cell growth. |
RNA sequencing, whole exome sequencing, siRNA knockdown of fusion transcript, cell growth assay |
Cancer science |
Low |
31222839
|