Initial LOEUF Constraint Analysis

LOEUF distributions by functional category and disease class

Overview

Baseline analysis of LOEUF (Loss-of-Function Observed/Expected Upper bound fraction) across the 129-gene Raghunath melanocyte signaling network, stratified by functional category and by disease class.

LOEUF by functional category

Genes in the Raghunath network classified into six functional categories. Kruskal-Wallis test with Dunn’s posthoc (Bonferroni correction).

LOEUF by disease class

Genes classified as syndromic/pleiotropic vs. isolated pigmentation phenotype.

Key result: Complete separation between disease classes — syndromic/developmental genes are universally constrained (low LOEUF), while isolated pigmentation genes are LoF-tolerant (high LOEUF), p = 1.36e-04.

Summary statistics

	N	Median LOEUF	Mean LOEUF
functional_category
Pigment-specific	7	1.889	1.584
Developmental/NC	8	0.364	0.401
Generic signaling	47	0.334	0.377
Cytokines/growth factors	14	0.593	0.719
Apoptosis/cell death	18	0.781	0.937
Other	35	0.755	0.792