FIGURE 6

FIGURE 6

ITPR1 is involved in different pathways. (A) It has been illustrated by several reports that the EDN-EDNRA-G protein α_q-DLX5/6 axis has important roles in mandible formation. EDN binds to receptor EDNRA, a G-protein that can activate PLCB4. PLCB4 splits PIP2, membrane-bound phospholipids, into DAG and IP3. IP3 binds to its receptor ITPR1, a calcium release channel, to allow the passage of calcium to move through. Calcium works to activate PKC and Rap, and stimulate MAPK signaling, which can regulate Dlx5 and Dlx6 expression. (B) The network of protein-protein interaction is shown, produced by STRING software (https://string-db.org), including ITPR1 and its closest partner PLCB4. EDN1 and EDNRA genes may be involved in craniofacial development especially those reported as a causative protein of human mandibular deformities, and among those with gene mutation have been reported in HM patients, like MYT1 and EFTUD2.