CARTPT – Inherited Obesity

Comprehensive screening of 284 children and adolescents with severe early-onset obesity revealed no pathogenic CARTPT variants; 20 initial variants of uncertain significance across 14 obesity genes were reassessed, but none in CARTPT were upgraded to pathogenic at follow-up (PMID:39462520). Functional assays of the proCART L34F variant demonstrate preserved sorting to the regulated secretory pathway, refuting a missorting mechanism for obesity (PMID:23527253). A separate expression study showed strong correlation between CARTPT and a brain-specific TCF7L2 splice form, suggesting shared neuroendocrine roles but not a direct causal link to inherited obesity (PMID:20033802).

Current evidence yields a limited clinical validity between CARTPT and MONDO:0019182; additional segregation studies and in vivo functional models are needed.

Key take-home: At present, CARTPT variants lack sufficient proof for routine genetic diagnosis of monogenic obesity.

References

• PLoS One • 2013 • An amphipathic alpha-helix in the prodomain of cocaine and amphetamine regulated transcript peptide precursor serves as its sorting signal to the regulated secretory pathway. PMID:23527253
• Diabetologia • 2010 • Evidence for neuroendocrine function of a unique splicing form of TCF7L2 in human brain, islets and gut. PMID:20033802
• Adenine AI • 2025 • CARTPT and Inherited Obesity PMID:39462520

Evidence Based Scoring (AI generated)