Search for patients with biallelic variants in genes implicated in the ufmylation pathway

Targeted gene(s)/phenotype under study :

  • Gene:  UBA5, UFM1, UFC1,UFL1 and MRE11 (OMIM# 617132, # 617899, # 618076, # 604391)

Abstract :

The covalent attachment of the ubiquitin-fold modifier1 (UFM1) to a target protein, also named ufmylation, is a recently identified ubiquitin-like post-translational modification, ubiquitously expressed. Similarly to ubiquitination, ufmylation requires a series of enzymes referred to as E1 activating enzyme (UBA5), E2 conjugating enzyme (UFC1), and E3 ligase (UFL1) to transfer UFM1 to its targets. The molecular and cellular functions of UFMylation remains poorly understood. Biallelic variants in UBA5, UFM1 and UFC1 have been involved in neurodevelopmental disorders with often early encephalopathy, hypomyelination, acquired microcephaly, movement disorders or spasticity, thus pointing the importance of this pathway for the brain development.

Recently publications showed that ufmylation of the nuclease MRE11 regulate ATM activation and double strand break repair.

We are collecting patients with biallelic variants in UBA5, UFM1, UFL1, UFC1 and MRE11 (even patients who have already been published) to further describe the phenotype and to identify the molecular and cellular determinants regulated by the UFM1 pathway.

Coordinating clinicians /researchers: 

  • Dr Estelle Colin
  • Dr Christophe Lachaud


Institution :

Medical Genetic Department

Angers University Hospital

Angers, France



Inserm UMR1068, CNRS UMR7258, Université U105, Institut Paoli Calmettes

Marseille, France

Contact : 

Specific requirements beyond clinical data and genotype data sharing:

  • Re-analysis of DNA samples : N
  • Resampling of patients : Y
  • Linked to a translational/basic research project? Y