Is there any disease mainly caused by underexpression or overexpression of some proteins?

Question

[vincent.bioscience]

Is there any disease mainly caused by underexpression or overexpression of some proteins?

Answer 1

[harold.smith.tarheel]

Any of the cytologically detectable deletions or duplications that are dominant disease markers (such as trisomy 21, mentioned by @Asaf) are presumed to decrease/increase gene expression levels.

Haplo-insufficient genes produce disease when one of the two copies is absent (e.g., Williams syndrome or Rubinstein-Taybi syndrome). Alpha-thalassemia (four copies) manifests as different diseases depending upon how many copies are deleted.

For overexpression examples, increased PKD1 causes polycystic kidney disease, and PLP1 duplication causes Pelizaeus–Merzbacher disease.

[WouterDeCoster]

To add to the list: SNCA duplication and triplication causes Parkinson Disease, APP duplication causes Alzheimer Disease. Heterozygous loss of GRN causes Frontotemporal Dementia.

Answer 2

[Asaf]

I guess that Down Syndrome is a case where a lot of genes are over-expressed due to an extra copy.

Answer 3

[WouterDeCoster]

Yes, such as diseased caused by gene deletions or other loss of function variants i.e. nonsense variants or frameshifts leading to a premature stop codon.

[Jean-Karim Heriche]

Plus cases where pathogens modulate the host's gene/protein expression patterns, e.g. viruses that modulate cytokines expression levels.

Answer 4

[Kevin Blighe]

Breast cancer and CCND1.

• Overexpression results in cell proliferation
• Underexpresion compromises DNA damage repair pathways

Answer 5

[John]

Type-2 Diabetes is a neato example of something that's a combination of both.