CABLES1
Chr 18Cdk5 and Abl enzyme substrate 1
Also known as: CABL1, CABLES, HsT2563, IK3-1
The CABLES1 protein regulates cell cycle progression by binding to cyclin-dependent kinases and enhancing their tyrosine phosphorylation, which is critical for neuronal development and outgrowth. Mutations in CABLES1 cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. This gene is moderately constrained against loss-of-function variants, primarily affecting the nervous system during early development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
174 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 34 | 0 | 34 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 109 | 8 | 0 | 117 |
Likely Benign | 0 | 5 | 0 | 1 | 6 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 0 | 114 | 43 | 1 | 159 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CABLES1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools