ADGRG6

Chr 6

adhesion G protein-coupled receptor G6

The protein is an adhesion G-protein coupled receptor that binds steroid hormones like progesterone and signals through G proteins to regulate adenylate cyclase, playing roles in peripheral nervous system myelination, blood-brain barrier formation, and bone development. Mutations cause autosomal recessive polymicrogyria, megalencephaly, and hydrocephalus (PMGYSH), affecting brain development and structure. This gene is highly constrained against loss-of-function variants (LOEUF 0.468), indicating that complete loss of protein function is likely pathogenic.

ResearchSummary from RefSeq, UniProt

Adhesion G protein-coupled receptor (aGPCR) for steroid hormones, such as progesterone and 17alpha-hydroxyprogesterone (17OHP) (PubMed:35394864, PubMed:39884271). Involved in many biological processes, such as myelination, sprouting angiogenesis, placenta, ear and cartilage development (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:24227709, PubMed:35394864). ADGRG6 is coupled to G(i) G alpha proteins and mediates inhibition of adenylate cyclase (PubMed:24227709, PubMed:35394864). Also able to couple to G(q) G proteins (PubMed:24227709). Involved in myelination of the peripheral nervous system: required for differentiation of promyelinating Schwann cells and for normal myelination of axons (PubMed:24227709). Also acts as a regulator of body length and bone mass (PubMed:18391950). Acts as a regulator of blood-brain barrier formation in the central nervous system vie its association with LRP1 and ITGB1 (By similarity)

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLethal congenital contracture syndrome 9

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.47

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (2)

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