ADAM22

Chr 7AR

ADAM metallopeptidase domain 22

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.361 OMIM phenotype
Clinical SummaryADAM22
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Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.36LOEUF
pLI 0.251
Z-score 5.53
OE 0.23 (0.150.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.34Z-score
OE missense 0.70 (0.640.77)
349 obs / 495.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.23 (0.150.36)
00.351.4
Missense OE0.70 (0.640.77)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 14 / 60.4Missense obs/exp: 349 / 495.6Syn Z: 0.27
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongADAM22-related developmental and epileptic encephalopathyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6161th %ile
GOF
0.6150th %ile
LOF
0.4136th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ADAM22 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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