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Impaired gephyrin G-domain trimerization and phase separation in a patient with developmental epileptic encephalopathy.

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1 match between paragraphs of the paper and lines of its authors' code, computed by the harvester (lexical-v1). Click a colored paragraph or line to see its counterpart.

The 1 match
  1. [1] § Results › G134R-gephyrin disrupts neuronal clustering and acts dominant negatively when co-expressed with WT-gephyrin ↔ G134R_extended_data_code/5_summarize_measurements/summary_for_HET.py, lines 7–80 · score 0.59 · mEGFP, mScarlet, synaptic cluster, vGAT, density, neurons

Paper

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The authors' code

Python · 88 lines · 3.3 KB · MIT · 1 match

  1. import statistics
  2. import pandas as pd
  3. import os
  5. folder = r"Z:/personal_data/Filip_Liebsch/SP8_Biocenter_small/2025-04-23_floxed/G134R_HET_project/data/"
  7. def execute(root, tbl):
  8. print(f"Found table in: {root}")
  9. table_path = os.path.join(root, tbl)
  10. df = pd.read_csv(table_path, sep="\t")
  12. #2520 pixels 144.78 µm --> 0.057452380952 µm --> 0.003300776071
  13. df['ClusterSize'] = df['mEGFP-Gphn_area'] * 0.003300776071
  14. df['Cluster'] = df['ClusterSize'].between(0.1, 1)
  15. # synaptic clusters inside cell
  16. cell_syn_cluster_cols = ['vGAT', 'Neuron', 'Cluster', 'mScarlet-Gphn']
  17. cell_syn_mask = df[cell_syn_cluster_cols].all(axis=1)
  18. cell_syn_clusters = cell_syn_mask.sum()
  19. cell_syn_density = cell_syn_clusters/(df['Neuron_area'].iloc[0] * 0.003300776071)
  21. # synaptic clusters inside soma
  22. soma_syn_cluster_cols = ['vGAT', 'Soma', 'Cluster', 'mScarlet-Gphn']
  23. soma_syn_mask = df[soma_syn_cluster_cols].all(axis=1)
  24. soma_syn_clusters = soma_syn_mask.sum()
  25. soma_syn_density = soma_syn_clusters/(df['Soma_area'].iloc[0] * 0.003300776071)
  27. # synaptic cluster ratio
  28. cell_cluster_cols = ['Neuron', 'Cluster']
  29. cell_cluster_mask = df[cell_cluster_cols].all(axis=1)
  30. cell_clusters = cell_cluster_mask.sum()
  31. cell_synaptic_ratio = cell_syn_clusters/cell_clusters
  34. # area
  35. mean_area = df.loc[cell_syn_mask, 'ClusterSize'].mean()
  37. # intensity
  38. mean_intensity = df.loc[cell_syn_mask, 'mEGFP-Gphn_mean'].mean()
  40. # cell parameters
  41. soma_area = df['Soma_area'].iloc[0] * 0.003300776071
  42. neuron_area = df['Neuron_area'].iloc[0] * 0.003300776071
  44. # cell intensity parameters
  45. neuron_mEGFP_mean = df['Neuron_mEGFP-Gphn_mean'].iloc[0]
  46. soma_mEGFP_mean = df['Soma_mEGFP-Gphn_mean'].iloc[0]
  47. neuron_mScarlet_mean = df['Neuron_mScarlet-Gphn_mean'].iloc[0]
  48. soma_mScarlet_mean = df['Soma_mScarlet-Gphn_mean'].iloc[0]
  50. # cell info
  51. date = df['date'].iloc[0]
  52. condition = df['condition'].iloc[0]
  53. cell = df['cell'].iloc[0]
  55. # information summary dataframe
  56. statistics = {
  57. 'synaptic_cell_density': [cell_syn_density],
  58. 'synaptic_soma_density': [soma_syn_density],
  59. 'synaptic_ratio': [cell_synaptic_ratio],
  60. 'mean_synaptic_area': [mean_area],
  61. 'mean_synaptic_intensity': [mean_intensity],
  62. 'soma_area': [soma_area],
  63. 'neuron_area': [neuron_area],
  64. 'neuron_mEGFP_mean': [neuron_mEGFP_mean],
  65. 'soma_mEGFP_mean': [soma_mEGFP_mean],
  66. 'neuron_mScarlet_mean': [neuron_mScarlet_mean],
  67. 'soma_mScarlet_mean': [soma_mScarlet_mean],
  68. 'date': [date],
  69. 'condition': [condition],
  70. 'cell': [cell]
  71. }
  74. df_summary = pd.DataFrame(statistics)
  77. path_norm = os.path.normpath(root)
  78. path_list = path_norm.split(os.sep)
  80. df_summary.to_csv(os.path.join(root, path_list[-5] + "_cluster_summary_" + path_list[-4] + "_" + path_list[-3] + ".tsv"), sep="\t")
  83. for root, dirs, files in os.walk(folder):
  84. for file in files:
  85. if file.lower().endswith(".tsv") and "cluster_analysis" in file.lower():
  86. execute(root, file)
  88. print("...completed.")

summary_for_HET.py at commit ca30d7c, under MIT · at the source

Overview

Authors: Emanuel H W Bruckisch1, Marcelo de Melo Aragão2, Thais dos Santos Rohde2, Ann-Kathrin Huber1, Mateus de Oliveira Torres2, Günter Schwarz1,3,4, Filip Liebsch1
ORCID iDs: Emanuel H W Bruckisch, Günter Schwarz, Filip Liebsch
  1. Institute of Biochemistry, Department of Chemistry, University of Cologne, 50674 Cologne, Germany
  2. Department of Neurology & Neurosurgery, University Hospital São Paulo, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
  3. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
  4. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
Institutions: University of Cologne (Germany); Hospital São Paulo (Brazil); Universidade Federal de São Paulo (Brazil); Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (Germany)
Journal: EMBO molecular medicine, volume 18, issue 8, pages 3157-3174
Dates: received 9 January 2026; accepted 9 June 2026; published online 30 June 2026; in print August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s44321-026-00474-w · PMID 42380307 · PMCID PMC13470343 · OpenAlex W7166639026
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: human (organism), other condition (population), epilepsy (population), cellular / molecular (subfield)
Methods: Connectivity, Statistics, Machine learning, Spectral & time-frequency
Keywords: Genetics, Gene Therapy & Genetic Disease, Neuroscience
MeSH: Carrier Proteins*, Epilepsy*, Membrane Proteins*, Protein Multimerization*, Animals, Humans, Metalloproteins, Molybdenum Cofactors, Mutation, Missense, Neurons, Phase Separation, Protein Domains, Receptors, Glycine (* major topic)
Topic: Plant biochemistry and biosynthesis (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Deutsche Forschungsgemeinschaft (DFG) (RTG2550/1736 project ID 411422114)
Citations: not cited yet (Europe PMC); 43 references in the paper
Research resources: Anti-GephE (3B11) RRID:AB_887719, pAAV2/1 RRID:Addgene_112862, The plasmids pAdDeltaF6 RRID:Addgene_112867, RRID:Addgene_131001

Abstract

Epilepsy, a common neurological disorder is frequently linked to genetic variants in synaptic proteins. Here, we describe a de novo pathogenic missense variant in the gephyrin G-domain (G134R) identified in an individual with developmental delay, epileptic seizures, microcephaly, dysmorphic features and short stature. Functional analyses reveal that G134R disrupts higher-order oligomerization, leading to impaired liquid–liquid phase separation (LLPS) and synaptic clustering. Recombinant G134R-gephyrin variant forms lower oligomers and retains only 60% of its molybdenum cofactor (Moco) synthesis activity while binding to glycine receptor models is unaffected. In non-neuronal cells, G134R fails to oligomerize beyond dimers with Moco synthesis activity reduced to 5%. In neurons, G134R is unable to form synaptic clusters and exerts a dominant-negative effect on WT-gephyrin, severely disrupting inhibitory synapse formation. Our findings highlight a critical role for the G-domain in gephyrin self-assembly and LLPS, shifting the focus from the E-domain-centric view of gephyrin function and providing a novel molecular mechanism for epilepsy linked to G-domain mutations.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above, with 1 match between paragraphs and lines of code.

FilLieb/automated_synapse_analysis

License: MIT
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: ca30d7c2276977a1cda961394c718a6f5ab0eb94, 11 May 2026
Languages: Python (11)
Size: 53 files, 11 scripts
Software Heritage: not archived
Found in: the text, “Confocal microscopy and image analysis”
Holds: README, license file
Not found: CITATION.cff, environment file, tests, continuous integration, documentation
Tools: pandas (6 files), scikit-image (5 files), NumPy (4 files), SciPy (2 files), Matplotlib (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
13 files
At the source: github.com/FilLieb/automated_synapse_analysis

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  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 11 scripts, each with its path and the digest of its content;
  • 1 match between paragraphs of the paper and lines of the code (method lexical-v1);
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Data

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The source data of this paper are collected in the following database record: biostudies:S-SCDT-10_1038-S44321-026-00474-w (https://www.ebi.ac.uk/biostudies/sourcedata/studies/S-SCDT-10_1038-S44321-026-00474-w).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 3 keywords, 13 MeSH terms, 1 funder, 43 references, 4 RRIDs.

Cite

This paper

Bruckisch, E. H. W., de Melo Aragão, M., dos Santos Rohde, T., Huber, A.-K., de Oliveira Torres, M., Schwarz, G., & Liebsch, F. (2026). Impaired gephyrin G-domain trimerization and phase separation in a patient with developmental epileptic encephalopathy. EMBO molecular medicine, 18(8), 3157-3174. https://doi.org/10.1038/s44321-026-00474-w

BibTeX

@article{bruckisch2026impaired,
author = {Bruckisch, Emanuel H W and de Melo Aragão, Marcelo and dos Santos Rohde, Thais and Huber, Ann-Kathrin and de Oliveira Torres, Mateus and Schwarz, Günter and Liebsch, Filip},
title = {{Impaired gephyrin G-domain trimerization and phase separation in a patient with developmental epileptic encephalopathy}},
journal = {EMBO molecular medicine},
year = {2026},
month = jun,
volume = {18},
number = {8},
pages = {3157--3174},
publisher = {Nature Publishing Group},
issn = {1757-4676},
doi = {10.1038/s44321-026-00474-w},
url = {https://doi.org/10.1038/s44321-026-00474-w},
pmid = {42380307},
pmcid = {PMC13470343}
}

RIS

TY - JOUR
AU - Bruckisch, Emanuel H W
AU - de Melo Aragão, Marcelo
AU - dos Santos Rohde, Thais
AU - Huber, Ann-Kathrin
AU - de Oliveira Torres, Mateus
AU - Schwarz, Günter
AU - Liebsch, Filip
TI - Impaired gephyrin G-domain trimerization and phase separation in a patient with developmental epileptic encephalopathy
T2 - EMBO molecular medicine
J2 - EMBO Mol Med
PY - 2026
DA - 2026/06/30
VL - 18
IS - 8
SP - 3157
EP - 3174
SN - 1757-4676
PB - Nature Publishing Group
DO - 10.1038/s44321-026-00474-w
UR - https://doi.org/10.1038/s44321-026-00474-w
LA - en
ER -

CSL-JSON

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"author": [
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