ADAM12

Pathway Information

ADAM12 is an enzyme that consists of two splice variants: ADAM12-L, the long form, has a transmembrane region and ADAM12-S, a shorter variant.

In a study of about 1200 persons with extremely high intelligence (IQ about 170, representing the top 0.0003 of the population), variants of the ADAM12 gene (increased levels) were associated with high IQ compared with a general population [1]. The researchers discovered genetic variants in locus ADAM12 that were linked to enhanced cognitive abilities and educational attainment.

The ADAM12-related genes rs4962322, rs4962520 and rs10794073 were most significantly associated in the study.

Furthermore, subsequent pathway analysis revealed that the plexin gene family was enriched in the extreme IQ population. Plexins function as receptors for semaphorins and play a critical role in axon guidance and development.

One interesting observation is that DNA methylation of cg15280358 in ADAM12 has been associated with lifetime cannabis use [3].

Modulating ADAM12 seems quite tricky, as there are limited studies on it. One approach may be through IGFBP-3. ADAM12 binds insulin growth factor binding protein-3 (IGFBP-3), so targeting IGFBP-3 may potentially carry some of the same effects when ADAM12 is modulated [2].

Also something like intranasal IGF-1 might rely on some of the same pathways ADAM12 does, so it may be a similar option even if no direct way to modulate ADAM12 without gene editing is found.