The vast majority of missense variants observed in the human genome are of unknown
clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on …

With the development of next-generation sequencing technology, de novo variants (DNVs)
with deleterious effects can be identified and investigated for their effects on birth defects …

Next-generation sequencing (NGS) has revolutionized the field of rare disease diagnostics.
Whole exome and whole genome sequencing are now routinely used for diagnostic …

Mutations, which result in amino acid substitutions, influence the stability of proteins and
their binding to biomolecules. A molecular understanding of the effects of protein mutations …

Strong efforts have been placed on understanding the physiological roles and therapeutic
potential of the proglucagon peptide hormones including glucagon, GLP-1 and GLP-2 …

In Type 2 diabetes, increased insulin sensitivity is induced by thiazolidinedione activation of
the peroxisome proliferator-activated receptor gamma (PPARγ). Recent data indicate a …

While pathogenic variants can significantly increase disease risk, it is still challenging to
estimate the clinical impact of rare missense variants more generally. Even in genes such as …

The use of induced pluripotent stem cells (iPSCs) is a promising approach when used as
models to study neurodegenerative disorders (NDDs) in vitro. iPSCs have been used in in …

The PAX6 gene encodes a highly-conserved transcription factor involved in eye
development. Heterozygous loss-of-function variants in PAX6 can cause a range of …

Intrinsically disordered regions (IDRs) are protein regions that are unable to fold into stable
tertiary structures, enabling their involvement in key signaling and regulatory functions via …