CLSTN3

Chr 12

calsyntenin 3

Also known as: CDHR14, CSTN3, alcbeta

NCBI Gene: 9746ENSG00000139182UniProt: Q9BQT9

CLSTN3 encodes a postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate both excitatory and inhibitory synapse formation and regulates the balance between these synapse types. Mutations cause autosomal dominant neurodevelopmental disorders affecting cognitive function and behavior. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to have significant clinical consequences.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
46
P/LP submissions
0%
P/LP missense
0.32
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— CLSTN3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
45 unique Pathogenic / Likely Pathogenic· 144 VUS of 224 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
0.32LOEUF
pLI 0.970
Z-score 4.98
OE 0.17 (0.09–0.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.50Z-score
OE missense 0.83 (0.77–0.89)
487 obs / 589.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.09–0.32)
0≤0.351.4
Missense OE0.83 (0.77–0.89)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 7 / 41.7Missense obs/exp: 487 / 589.3Syn Z: -0.17
DN
0.4190th %ile
GOF
0.4580th %ile
LOF
0.64top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.32

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

224 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic2
VUS144
Likely Benign5
Benign3
43
Pathogenic
2
Likely Pathogenic
144
VUS
5
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
2
0
2
VUS
0
133
11
0
144
Likely Benign
0
1
0
4
5
Benign
0
1
1
1
3
Total0135575197

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

View in ClinVar →

Protein Context — Lollipop Plot

CLSTN3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

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