L1CAM
Chr XXLRL1 cell adhesion molecule
Also known as: CAML1, CD171, HSAS, HSAS1, HYCX, MASA, MIC5, N-CAM-L1
L1CAM encodes a neural cell adhesion molecule that mediates cell-cell adhesion and generates transmembrane signals, playing critical roles in neuronal migration, axonal growth and fasciculation, and synaptogenesis during brain development. Loss-of-function mutations cause X-linked recessive neurological syndromes including CRASH syndrome (corpus callosum hypoplasia, intellectual disability, aphasia, spastic paraplegia, and hydrocephalus), MASA syndrome, and X-linked congenital hydrocephalus. The pathogenic mechanism involves loss of protein function leading to disrupted neural development and connectivity.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
500 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 | 26 | 1 | 23 | 0 | 50 |
Likely Pathogenic | 18 | 5 | 1 | 0 | 24 |
VUS | 2 | 118 | 14 | 2 | 136 |
Likely Benign | 1 | 30 | 67 | 81 | 179 |
Benign | 0 | 11 | 6 | 16 | 33 |
Conflicting | — | 2 | |||
| Total | 47 | 165 | 111 | 99 | 424 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
L1CAM · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
RECRUITINGRefining Fertility-sparing Treatment in Endometrial Carcinoma Based on Molecular Classification
RECRUITINGExternal Resources
Links to major genomics databases and tools