CNTNAP3

Chr 9

contactin associated protein family member 3

Also known as: CASPR3, CNTNAP3A

NCBI Gene: 79937ENSG00000106714UniProt: Q9BZ76OMIM: 610517

The encoded protein is a cell-recognition molecule that mediates neuron-glial interactions within the nervous system. Mutations cause autosomal recessive neurodevelopmental disorders including developmental and epileptic encephalopathy, intellectual disability, and cortical visual impairment with onset in infancy or early childhood. This gene shows minimal constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 0.77
Clinical Summary— CNTNAP3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 unique Pathogenic / Likely Pathogenic· 197 VUS of 282 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.000
Z-score 2.82
OE 0.55 (0.40–0.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.15Z-score
OE missense 0.98 (0.91–1.06)
518 obs / 527.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.55 (0.40–0.77)
0≤0.351.4
Missense OE0.98 (0.91–1.06)
0≤0.61.4
Synonymous OE1.14
0≤1.21.6
LoF obs/exp: 25 / 45.5Missense obs/exp: 518 / 527.4Syn Z: -1.57
DN
0.7327th %ile
GOF
0.6344th %ile
LOF
0.2582th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

282 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic5
VUS197
Likely Benign17
Benign1
Conflicting1
46
Pathogenic
5
Likely Pathogenic
197
VUS
17
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
46
0
46
Likely Pathogenic
0
0
5
0
5
VUS
0
195
2
0
197
Likely Benign
0
12
1
4
17
Benign
0
0
0
1
1
Conflicting
—1
Total0207545267

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

View in ClinVar →

Protein Context — Lollipop Plot

CNTNAP3 · 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 4 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