Happy to share our newest preprint on Parkin missense variants in work led by Erna Sol & @vvouts.bsky.social in @rhp-lab.bsky.social Using a multiplexed assay we determined the effects of 9,212 out of 9,300 single amino acid substitutions and nonsense Parkin variants. 1/n doi.org/10.64898/202...

We map the effects of >99% Parkin (PRKN) missense variants on mitophagy. The landscape separates benign & pathogenic variants, reveals misfolded variants induce mitophagy and flags hypomorphic alleles for rescue. Collab w. @lindorfflarsen.bsky.social. Work led by Erna Sol & @vvouts.bsky.social.

A near-complete map of human cytosolic degrons and their relevance for disease We measured degron potency of >200,000 30-residue tiles from >5,000 human proteins, and trained a model to predict degrons from sequence Led by @vvouts.bsky.social in @rhp-lab.bsky.social doi.org/10.1126/scia...

Now on bioRxiv: genome‑wide CRISPR KO reveals BAG6 (chaperone) and RNF126 (E3) as core PQC for non‑native missense proteins. VAMP seq. shows >1000 Parkin variants are BAG6 targets, including known pathogenic variants. Work led by Line Pedersen. Collab with @lindorfflarsen.bsky.social

BAG6 and RNF126 are broadly involved in protein quality control of non-native missense protein variants https://www.biorxiv.org/content/10.64898/2026.02.04.703735v1

Second preprint of the year in which @sarahgersing.bsky.social from @rhp-lab.bsky.social mapped the effects of >7500 variants in glucokinase (GCK) on the interaction with the glucokinase regulatory protein so that we now have a 3D GCK scan (abundance, interaction, activity) doi.org/10.64898/202...

New preprint! Led by @sarahgersing.bsky.social we map how 7,500+ variants in glucokinase (GCK) affect binding to GKRP and disentangle this from stability. We now have activity, abundance, and interaction scores for 7,128 GCK variants - a resource for understanding phenotypes and glucose homeostasis.

The proteasome-substrate-shuttle protein UBQLN2 contains—like other quality control system proteins—a long region devoid of lysine (a lysine desert) Martin Grønbæk-Thygesen (from @rhp-lab.bsky.social) et al show that introducing K here causes ubiquitylation and degradation doi.org/10.1101/2025...

Martin Grønbæk-Thygesen in @rhp-lab.bsky.social measured abundance and toxicity (both independently of function) of missense variants in aspartoacylase, and found that a subset of the low-abundance variants were toxic, induced a stress response which correlated with toxicity doi.org/10.1038/s414...

I’m biased 🇩🇰, but this is quite nice to read: I thought science hinged on prestige. Moving abroad made me reassess my priorities www.science.org/content/arti...

We are back with an exciting seminar on September 8 at 3pm CEST! We’ll hear from Prof. Birthe Kragelund and Maximilian Vieler (@uu.se). Register to attend: tinyurl.com/PMCseminar2 Recordings of previous seminars: www.youtube.com/@PMCModularity

I'm looking for my first PhD student! We will push the frontiers of probabilistic machine learning for the molecular sciences, and study how to design new algorithms that exploit the unique properties of molecular systems to learn about the world. efzu.fa.em2.oraclecloud.com/hcmUI/Candid...

Both translational and fundamental curiosity-driven research are needed to fuel the incredible progress we're seeing in genomic medicine; an important message in this article and and some lovely quotes from @sarahlwynn.bsky.social www.ft.com/content/25dd...

@lindorfflarsen.bsky.social at #VariantEffect25

With the @lindorfflarsen.bsky.social group we present our map of degrons in all human transcription factors, incl. examples of constitutive degrons in exposed regions & buried degrons that are exposed upon mutation. In addition, we show that most TADs overlap with degrons. Work led by Fia Larsen.

In collaboration with the @lindorfflarsen.bsky.social group we release our map of degrons in >5,000 human cytosolic proteins with >99% coverage. A machine learning model trained on the data identifies missense variants forming degrons in exposed & disordered regions. Work led by @vvouts.bsky.social.

We are looking for a PhD student with interest in protein biochemistry on a really cool project “Cooperation of deubiquitinating enzymes and VCP/p97 in cellular stress responses”. Build your own reactions! fully funded. apply with code 193-25. #ubiquitin

... wait! There's more great Review content! ☘️ mechanisms of #SAM homeostasis (Ben Tu et al) ☘️ glucose sensing by #glucokinase and how disease variants impact its function @sarahgersing.bsky.social @lindorfflarsen.bsky.social @rhp-lab.bsky.social

Now online - the Review "#Glucokinase: from allosteric glucose sensing to disease variants" from @sarahgersing.bsky.social, Torben Hansen, @lindorfflarsen.bsky.social, and @rhp-lab.bsky.social. #GlucoseHomeostasis #GlucoseSensor #GCKMODY #CooperativeKinetics authors.elsevier.com/a/1kN5M3S6Gf...

Happy to share our review, 'Glucokinase: from allosteric glucose sensing to disease variants', published in @cp-trendsbiochem.bsky.social, which explores the fascinating enzyme glucokinase. authors.elsevier.com/a/1kN5M3S6Gf...

In our new paper we characterize the effects of indel variants on protein folding and stability using a new yeast-based protein folding sensor. The work was led by Sven Larsen-Ledet and supported by the @novo-nordisk.bsky.social. Link to paper: www.cell.com/structure/fu...