CADM2

Chr 3

cell adhesion molecule 2

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

NCBI Gene: 253559 ENSG00000175161 UniProt: Q8N3J6

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the synaptic cell adhesion molecule 1 (SynCAM) family which belongs to the immunoglobulin (Ig) superfamily. The encoded protein has three Ig-like domains and a cytosolic protein 4.1 binding site near the C-terminus. Proteins belonging to the protein 4.1 family crosslink spectrin and interact with other cytoskeletal proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ResearchGenerating clinical summary…

LOEUF 0.38

Clinical Summary— CADM2

⚡

Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.

📋

ClinVar Variants

34 VUS of 47 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.38LOEUF

pLI 0.891

Z-score 3.57

OE 0.15 (0.07–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.98Z-score

OE missense 0.64 (0.56–0.73)

151 obs / 236.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.07–0.38)

0≤0.351.4

Missense OE?0.64 (0.56–0.73)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 3 / 20.4Missense obs/exp: 151 / 236.6Syn Z: -1.60

ClinVar Variant Classifications

47 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

Benign4

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	34	0	0	34
Likely Benign	0	0	0	0
Benign	0	1	3	4
Total	34	1	3	38

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap CADM2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →