CHL1
Chr 3cell adhesion molecule L1 like
Also known as: CALL, L1CAM2
This gene encodes a neural cell adhesion molecule that facilitates cell recognition and signal transduction in the nervous system. Mutations cause an autosomal recessive developmental disorder characterized by intellectual disability, seizures, and congenital heart defects, with some patients also showing cohesinopathy-like features including growth retardation and limb malformations. The gene is highly constrained against loss-of-function variants, indicating that both copies are essential for normal neurodevelopment.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
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.
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
400 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 | 22 | 0 | 22 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 213 | 62 | 0 | 275 |
Likely Benign | 0 | 20 | 5 | 21 | 46 |
Benign | 0 | 6 | 6 | 7 | 19 |
Conflicting | — | 6 | |||
| Total | 0 | 239 | 99 | 28 | 372 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CHL1 · 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