CADM3

Chr 1AD

cell adhesion molecule 3

Also known as: BIgR, CMT2FF, IGSF4B, NECL1, Necl-1, TSLL1, synCAM3

NCBI Gene: 57863ENSG00000162706UniProt: Q8N126OMIM: 609743

CADM3 encodes a calcium-independent cell adhesion molecule that mediates cell-cell adhesion through homophilic and heterophilic interactions with other nectin proteins. Mutations cause autosomal dominant Charcot-Marie-Tooth disease, axonal type 2FF, a hereditary peripheral neuropathy. The gene is highly constrained against loss-of-function variants (pLI = 0.93, LOEUF = 0.36), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ADLOEUF 0.351 OMIM phenotype
Clinical Summary— CADM3
🧬
Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease, axonal, type 2FF · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 71 VUS of 110 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.35LOEUF
pLI 0.934
Z-score 3.74
OE 0.14 (0.06–0.35)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.69Z-score
OE missense 0.69 (0.61–0.79)
168 obs / 242.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.06–0.35)
0≤0.351.4
Missense OE0.69 (0.61–0.79)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 3 / 21.9Missense obs/exp: 168 / 242.1Syn Z: 0.05

ClinVar Variant Classifications

110 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic3
VUS71
Likely Benign10
Benign1
Conflicting2
6
Pathogenic
3
Likely Pathogenic
71
VUS
10
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
1
2
0
3
VUS
2
64
5
0
71
Likely Benign
0
1
1
8
10
Benign
0
0
1
0
1
Conflicting
—2
Total26615893

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

View in ClinVar →

Protein Context — Lollipop Plot

CADM3 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients