ACE

HIGH

Angiotensin-converting enzyme

Chromosome: 17q23.3

Gene Overview

ACE encodes angiotensin-converting enzyme, a zinc metallopeptidase that converts angiotensin I to angiotensin II and inactivates bradykinin. ACE is central to the renin-angiotensin-aldosterone system (RAAS) regulating blood pressure and fluid homeostasis. The insertion/deletion (I/D) polymorphism in intron 16 associates with circulating ACE activity; D allele confers higher enzyme levels. ACE influences vascular tone, aldosterone release, and cardiac remodeling. Expression is high in lung (vascular endothelium), kidney, and heart. ACE inhibitors are first-line antihypertensives. The gene links genetic variation to hypertension susceptibility and response to RAAS-blocking drugs.

Molecular Function

  • peptidyl-dipeptidase activity
  • angiotensin conversion
  • bradykinin degradation

Protein class: zinc metallopeptidase

Regulatory Annotation

Promoter activity: Endothelial-enriched; hypoxia-responsive elements.

Enhancer associations: ACE I/D polymorphism affects transcriptional efficiency.

eQTL tissues: lung, kidney

Tissue Expression Context

lungTPM range: 40-120GTEx vv8
kidneyTPM range: 25-80GTEx vv8

Pathways

Linked Diseases & Exposures

Diseases

Exposures

Mechanistic Hypotheses

Elevated ACE activity increases angiotensin II and reduces bradykinin; sustained vasoconstriction and aldosterone release elevate blood pressure; ACE I/D genotype modulates this pathway and hypertensive risk.

D allele associates with higher ACE levels and hypertension in meta-analyses; ACE inhibitors lower BP and reduce cardiovascular events.

HIGH

Confidence Rating

Overall evidence confidence for this gene entry: HIGH

References

  1. 1.Soubrier F, et al. (1988). Structure of angiotensin I-converting enzyme. Proceedings of the National Academy of Sciences. doi:10.1073/pnas.85.24.9386
  2. 2.GTEx Consortium (2020). GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science. doi:10.1126/science.aaz1776
  3. 3.Sayadi M, et al. (2020). Angiotensin-converting enzyme gene polymorphism and cardiovascular disease. Clinical and Experimental Hypertension. doi:10.1080/10641963.2019.1649685