ADAM22

Chr 7AR

ADAM metallopeptidase domain 22

Also known as: ADAM 22, DEE61, EIEE61, MDC2

NCBI Gene: 53616 ENSG00000008277 UniProt: Q9P0K1 OMIM: 603709

ADAM22 encodes a non-catalytic metalloprotease-like protein that functions as a neuronal receptor for LGI1 and serves as a probable integrin ligand in the brain, regulating cell adhesion and proliferation. Biallelic mutations cause developmental and epileptic encephalopathy 61 through autosomal recessive inheritance. The gene shows significant constraint against loss-of-function variation (LOEUF 0.363), reflecting its critical role in neuronal function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. Unlike other members of the ADAM protein family, the protein encoded by this gene lacks metalloprotease activity since it has no zinc-binding motif. This gene is highly expressed in the brain and may function as an integrin ligand in the brain. In mice, it has been shown to be essential for correct myelination in the peripheral nervous system. Alternative splicing results in several transcript variants.[provided by RefSeq, Dec 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 61MIM #617933

Clinical highlights

Gene-disease validity (ClinGen)

developmental and epileptic encephalopathy · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.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

0.36

LOEUF

Mechanism· predicted