CADM2

Chr 3

cell adhesion molecule 2

Also known as: IGSF4D, NECL3, Necl-3, SynCAM 2, SynCAM-2, synCAM2

The encoded protein is a synaptic cell adhesion molecule with three immunoglobulin-like domains that engages in homo- and heterophilic interactions to promote cell aggregation and synapse organization, with preferential binding to oligodendrocytes. Mutations cause autosomal recessive developmental and epileptic encephalopathy, typically presenting in infancy with seizures and developmental delays. This gene is highly constrained against loss-of-function variants, indicating that functional copies are critical for normal development.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.38
Clinical SummaryCADM2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 57 VUS of 87 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.38LOEUF
pLI 0.891
Z-score 3.57
OE 0.15 (0.070.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.98Z-score
OE missense 0.64 (0.560.73)
151 obs / 236.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.070.38)
00.351.4
Missense OE0.64 (0.560.73)
00.61.4
Synonymous OE1.22
01.21.6
LoF obs/exp: 3 / 20.4Missense obs/exp: 151 / 236.6Syn Z: -1.60

ClinVar Variant Classifications

87 submitted variants in ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS57
Likely Benign4
Benign8
7
Pathogenic
2
Likely Pathogenic
57
VUS
4
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
34
23
0
57
Likely Benign
0
0
4
0
4
Benign
0
0
5
3
8
Total03441378

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CADM2 · 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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