Genetics: NEGR1

Jonathan Edwards

Senior Member (Voting Rights)
A quick look on AI.

The
NEGR1 (Neuronal Growth Regulator 1) gene, located on chromosome 1p31.1, encodes a GPI-anchored cell adhesion molecule critical for brain development, synaptic organization, and neuronal connectivity. Strongly associated with obesity, depression, and neurodevelopmental disorders, NEGR1 regulates energy balance and synaptic plasticity. Studies suggest it plays a role in cognitive, emotional, and social behaviors.

Key Aspects of the NEGR1 Gene:
  • Function: As part of the IgLON family (including LSAMP, OPCML, NTRA, IGON5), NEGR1 acts as a cell adhesion molecule in the nervous system. It is involved in regulating synapse assembly, cholesterol homeostasis, and axon growth.
  • Disease Associations:
    • Obesity: Multiple GWAS studies consistently link NEGR1 variants with body mass index (BMI).
    • Neuropsychiatric/Developmental: NEGR1 deletions or dysfunction are linked to intellectual disability, developmental delays, autism spectrum disorder (ASD), dyslexia, anxiety, and depression.
    • Neurobiology: Deficiency in mice leads to altered dopamine/serotonin systems, reduced locomotor activity, and impaired social behavior.
    • Mechanism: It works as a trans-neural growth-promoting factor and is involved in modulating synaptic plasticity, particularly in corticolimbic circuits.
    • Expression: Predominantly expressed in the brain, including the hypothalamus, cortex, and hippocampus.
 
Looking at the gene cards for the non coding elements a number of these seem to be promoters/enhancers related to NEGR1. I guess not surprising given the proximity. But could here be something here (and potentially with other variants or near misses on significance) which means we’re seeing some, perhaps tissue specific, effects of relevant genes up or down regulated?

These can be seen in the relevant area on LocusZoom by toggling to show all features. But since I have new toys I ran them on the DecodeME data around NEGR1, lowering the significance threshold and looking specifically at the area of interest, which resulted in

ENSG00000225087
ENSG00000280317
KRT8P21
LINC01360
LINC02238
LINC02796
RN7SKP19
RNA5SP50
RNU6-1246P
 
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