MC4R Pathway Obesity Curation Project

Overview

Create a mechanism-centered dismech entry for obesity caused by disruption of the leptin-melanocortin-4 receptor pathway. The scope includes:

• acquired hypothalamic obesity
• congenital hypothalamic obesity
• syndromic obesity converging on MC4R signaling
• rare monogenic obesity involving LEP, LEPR, POMC, PCSK1, MC4R, SH2B1, and NCOA1

Modeling Choice

Use one umbrella disorder entry, Obesity_Due_to_MC4R_Pathway_Disruption.yaml, with has_subtypes to represent the major presentations and gene-defined monogenic forms. This follows the repo's spectrum-style pattern for disorders with a shared proximal mechanism and clinically important internal heterogeneity.

Do not create separate top-level disorder YAML files for each monogenic gene in this pass.

Expected Outputs

• kb/disorders/Obesity_Due_to_MC4R_Pathway_Disruption.yaml
• research/Obesity_Due_to_MC4R_Pathway_Disruption-deep-research-*.md
• research/Obesity_Due_to_MC4R_Pathway_Disruption-deep-research-*.md.citations.md
• references_cache/* for new PMIDs

Workflow

1. Create initial stub disorder entry.
2. Run deep research on the new disorder slug.
3. Curate mechanism, phenotypes, genetics, and treatments with PMID-backed evidence.
4. Validate schema, terms, references, and compliance.
5. Commit, push, and open a PR.

STATUS

• [x] Initial stub created
• [x] Deep research completed
• [x] YAML curated with evidence
• [x] Validation passed
• [ ] Commit pushed
• [ ] PR opened

NOTES

• Local MONDO search in this worktree surfaced MONDO:0019182 inherited obesity for monogenic obesity but not a single exact term covering the full umbrella of acquired, congenital hypothalamic, syndromic, and monogenic MC4R-pathway disruption. The entry is therefore seeded with the broader obesity disorder MONDO term and a more specific preferred term.
• Deep research completed with the asta provider in research/Obesity_Due_to_MC4R_Pathway_Disruption-deep-research-asta.md.