HEPACAM
Chr 11ARADhepatic and glial cell adhesion molecule
Also known as: GlialCAM, MLC2A, MLC2B
HEPACAM encodes a membrane protein that regulates cell motility and cell-matrix interactions, and in glia it targets the chloride channel CLCN2 to astrocytic processes where it regulates chloride flux involved in neuronal excitability. Mutations cause megalencephalic leukoencephalopathy with subcortical cysts, which can present as either a severe progressive form (type 2A) or a milder remitting form (type 2B) that may occur with or without intellectual disability. The gene shows high constraint against loss-of-function variants and follows both autosomal recessive and autosomal dominant inheritance patterns.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). 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.
Literature Evidence
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
192 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 | 2 | 4 | 35 | 0 | 41 |
Likely Pathogenic | 2 | 5 | 0 | 0 | 7 |
VUS | 0 | 59 | 29 | 0 | 88 |
Likely Benign | 0 | 7 | 13 | 14 | 34 |
Benign | 0 | 3 | 7 | 3 | 13 |
Conflicting | — | 6 | |||
| Total | 4 | 78 | 84 | 17 | 189 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HEPACAM · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools