CADM3

Chr 1

cell adhesion molecule 3

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

NCBI Gene: 57863 ENSG00000162706 UniProt: Q8N126

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.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a calcium-independent cell-cell adhesion protein that can form homodimers or heterodimers with other nectin proteins. The encoded protein has both homophilic and heterophilic cell-cell adhesion activity. This gene is reported to be a tumor suppressor gene. [provided by RefSeq, Oct 2016]

ResearchGenerating clinical summary…

LOEUF 0.35

Clinical Summary— CADM3

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Gene-Disease Validity (ClinGen)

Charcot-Marie-Tooth disease, axonal, type 2FF · ADModerate

Moderate evidence — consider for supplementary testing

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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.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 67 VUS of 99 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

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 OE?0.14 (0.06–0.35)

0≤0.351.4

Missense OE?0.69 (0.61–0.79)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 3 / 21.9Missense obs/exp: 168 / 242.1Syn Z: 0.05

ClinVar Variant Classifications

99 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS67

Likely Benign11

Benign1

Conflicting2

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	1	0	0	1
VUS	2	64	1	0	67
Likely Benign	0	1	1	9	11
Benign	0	0	1	0	1
Conflicting	—				2
Total	2	66	3	9	82

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap CADM3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →