CTNNAL1

Chr 9

catenin alpha like 1

Also known as: ACRP, CLLP, alpha-CATU

NCBI Gene: 8727ENSG00000119326UniProt: Q9UBT7OMIM: 604785

The protein enables actin filament binding and cadherin binding, and modulates Rho pathway signaling by providing a scaffold for the Lbc Rho guanine nucleotide exchange factor. Based on the extremely low pLI score, mutations in this gene are predicted to cause disease through a dominant-negative mechanism rather than loss of function. However, no specific disease phenotype has been established for CTNNAL1 mutations in humans.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
MultiplemechanismLOEUF 0.82
Clinical Summary— CTNNAL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 87 VUS of 147 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
0.82LOEUF
pLI 0.000
Z-score 2.46
OE 0.57 (0.41–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.69Z-score
OE missense 0.90 (0.82–0.98)
317 obs / 353.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.41–0.82)
0≤0.351.4
Missense OE0.90 (0.82–0.98)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 22 / 38.5Missense obs/exp: 317 / 353.4Syn Z: 0.76
DN
0.76top 25%
GOF
0.6540th %ile
LOF
0.2874th %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

147 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic5
VUS87
Likely Benign3
Benign2
31
Pathogenic
5
Likely Pathogenic
87
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
5
0
5
VUS
0
79
8
0
87
Likely Benign
0
1
0
2
3
Benign
0
1
1
0
2
Total081452128

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

View in ClinVar →

Protein Context — Lollipop Plot

CTNNAL1 · 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
Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis.
Su X et al.·J Orthop Surg Res
2023
Development and internal validation of a novel model and markers to identify the candidates for lymph node metastasis in patients with prostate cancer.
Cao HM et al.·Medicine (Baltimore)
2019Cohort
Catulin Based Reporter System to Track and Characterize the Population of Invasive Cancer Cells in the Head and Neck Squamous Cell Carcinoma.
Karpińska K et al.·Int J Mol Sci
2021
α-Catulin promotes cancer stemness by antagonizing WWP1-mediated KLF5 degradation in lung cancer.
Tung CH et al.·Theranostics
2022
Prognosis and tumor immune microenvironment of patients with gastric cancer by a novel senescence-related signature.
Zhang G et al.·Medicine (Baltimore)
2022Cohort
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CTNNAL1 promotes the structural integrity of bronchial epithelial cells through the RhoA/ROCK1 pathway.
Liu C et al.·Acta Biochim Biophys Sin (Shanghai)
2024Open Access
CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway.
Wu D et al.·Acta Biochim Biophys Sin (Shanghai)
2023Open AccessFunctional
Regulation of Cancer Stem Cells and Epithelial-Mesenchymal Transition by CTNNAL1 in Lung Cancer and Glioblastoma.
Kahm YJ et al.·Biomedicines
2023Open Access
CTNNAL1 enhances glucocorticoid sensitivity in HDM-induced asthma mouse model through deactivating hsp90 signaling pathway.
Wu D et al.·Life Sci
2023Functional
CTNNAL1 participates in the regulation of mucus overproduction in HDM-induced asthma mouse model through the YAP-ROCK2 pathway.
Wu D et al.·J Cell Mol Med
2022Open AccessFunctional
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