CTNNA2

Chr 2AR

catenin alpha 2

Also known as: CAP-R, CAPR, CDCBM9, CT114, CTNR

NCBI Gene: 1496ENSG00000066032UniProt: P26232OMIM: 114025

The protein functions as a linker between cadherin adhesion receptors and the cytoskeleton, regulating cortical neuronal migration and neurite growth by suppressing excessive actin branching. Mutations cause autosomal recessive cortical dysplasia with other brain malformations, affecting brain development during early life. The gene is highly constrained against loss-of-function variants, indicating its critical importance for normal neurological function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.381 OMIM phenotype
Clinical Summary— CTNNA2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 93 VUS of 166 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
0.38LOEUF
pLI 0.425
Z-score 4.82
OE 0.22 (0.14–0.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.63Z-score
OE missense 0.56 (0.51–0.62)
306 obs / 544.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.22 (0.14–0.38)
0≤0.351.4
Missense OE0.56 (0.51–0.62)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 10 / 44.8Missense obs/exp: 306 / 544.3Syn Z: -0.22
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCTNNA2-related disordered cortical neuronal migrationLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7132th %ile
GOF
0.6931th %ile
LOF
0.3842th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

166 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic3
VUS93
Likely Benign14
Benign27
14
Pathogenic
3
Likely Pathogenic
93
VUS
14
Likely Benign
27
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
10
0
14
Likely Pathogenic
2
0
1
0
3
VUS
2
71
19
1
93
Likely Benign
0
2
2
10
14
Benign
0
2
20
5
27
Total8755216151

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

View in ClinVar →

Protein Context — Lollipop Plot

CTNNA2 · 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
Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer: The Phase 3 EXTENTORCH Randomized Clinical Trial.
Cheng Y et al.·JAMA Oncol
2025Clinical trial
A novel intergenic (between REG3A and CTNNA2-AS1)-ALK fusion responds to alectinib in lung adenocarcinoma.
Liu Z et al.·Lung Cancer
2023Case report
A Decoy Oligodeoxynucleotides Disturbing Forkhead Box O3 Mediated ctnna2 Transcriptional Repression Prevents Postoperative Neurocognitive Disorder in Mice.
Wu Z et al.·CNS Neurosci Ther
2025
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
Monies D et al.·Hum Genet
2017
Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration.
Schaffer AE et al.·Nat Genet
2018
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